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Zuclopenthixoldihydrochlorid zur Behandlung von Schizophrenie

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Referencias

References to studies included in this review

Aaes‐Jorgensen 1981 {published data only}

Aaes‐Jorgensen T, Gravem A, Jorgensen A. Serum levels of the isomers of clopenthixol in patients given cis(Z)‐clopenthixol or cis(Z)‐trans(E)‐clopenthixol. Acta Psychiatrica Scandinavica Supplementum 1981;294:70‐7. [MEDLINE: 82178887; PMID 6951396]CENTRAL

Arango 2006 {published data only}

Arango C, Bombin I, Gonzalez‐Salvador T, Garcia‐Cabeza I, Bobes J. Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence. European Psychiatry 2006;21(1):34‐40. [MEDLINE: 16360311]CENTRAL
Bombin I, Arango C. Antipsychotic treatment adherence and violence in schizophrenia outpatients: a randomized prospective trial. European Neuropsychopharmacology 2004;14(Suppl 3):S289. CENTRAL

Balasubramanian 1991 {published data only}

Balasubramanian K, Baloch N, Briscoe MH, Chattree S, Cooper CJ, Durani SK, et al. A double blind multicentre comparison of oral zuclopenthixol and oral chlorpromazine in the treatment of acute psychosis. British Journal of Clinical Research 1991;n/a:149‐56. [MEDLINE: 69006168; PMID 5600894]CENTRAL

Ban 1975 {published data only}

Ban TA, Lehmann HE, Sterlin C, Climan M. Comprehensive clinical studies with thiothixene. Diseases of the Nervous System 1975;36(9):473‐7. [MEDLINE: 76021805; PMID 240651]CENTRAL
Lehmann HE, Ban TA. Thiothixene versus chlorprothixene versus clopenthixol. Psychopharmacology Bulletin 1970;6(4):118‐20. [13027]CENTRAL
Sterlin C, Ban TA, Jarrold L. The place of thiothixene among the thioxanthenes. Current Therapeutic Research Clinical and Experimental 1972;14(4):205‐14. [MEDLINE: 72182264; PMID 4623599]CENTRAL

CSzG Study ID 9828 2005 {published data only}

刘启珍, 王慧芳, 陈洪来, 刘翠珍. [Title only available in Chinese characters] [氯噻吨与氯丙嗪治疗精神分裂症的对照研究]. Shandong Archives of Psychiatry [山东精神医学] 2005;18(3):175‐6. CENTRAL

Dehnel 1968 {published data only}

Dehnel LL, Vestre ND, Schiele BC. A controlled comparison of clopenthixol and perphenazine in a chronic schizophrenic population. Current Therapeutic Research Clinical and Experimental 1968;10:169‐76. [MEDLINE: 68242121; PMID 4967871]CENTRAL

Fagerlund 2004 {published data only}

Fagerlund B, Mackeprang T, Gade A, Hemmingsen R, Glenthoj BY. Effects of low‐dose risperidone and low‐dose zuclopenthixol on cognitive functions in fisrt‐episode drug‐naive schizophrenic patients. CNS Spectrums. United States of America, 2004; Vol. 9, issue 5:364‐74. [MEDLINE: 15115949]CENTRAL

Fischer‐Cornelssen 1976 {published data only}

Fischer‐Cornelssen KA, Ferner UJ. An example of European multicentre trials: multispectral analysis of clozapine. Psychopharmacology Bulletin 1976;12:34‐9. CENTRAL

Glenthoj 2007 {published data only}

Glenthoj A, Glenthoj BY, Mackeprang T, Pagsberg AK, Hemmingsen RP, Jernigan TL, et al. Basal ganglia volumes in drug‐naive first‐episode schizophrenia patients before and after short‐term treatment with either a typical or an atypical antipsychotic drug. Psychiatry Research 2007;154(3):199‐208. [MEDLINE: 17360162]CENTRAL
Glenthoj B, Fagerlund B, Rasmussen H, Pinborg L, Svarer C, Friberg L, et al. Extrastriatal dopamine D2/D3‐receptors in drug‐naïve first‐episode schizophrenic patients: relation to psychopathology, cognition and treatment outcome. International Journal of Neuropsychopharmacology 2008;11(Suppl 1):6‐7. CENTRAL
Glenthoj B, Glenthoj A, Jagersma E, Pagsberg AK, Hemmingsen RP, Svarer C, et al. Effects of typical and atypical antipsychotic medication on caudate nucleus volume in first‐episode schizophrenic patients: relation to dopamine d2/3 receptor occupancy psychopathology and extrapyramidal side‐effects. Proceedings of the 8th World Congress of Psychiatry; 2005 Sep 10‐15; Cairo, Egypt. 2005. CENTRAL

Gravem 1978 {published data only}

Gravem A, Engstrand E, Guleng RJ. Cis(Z)‐clopenthixol and clopenthixol (Sordinol) in chronic psychotic patients. A double‐blind clinical investigation. Acta Psychiatrica Scandinavica 1978;58(5):384‐8. [MEDLINE: 79058923; PMID 362830]CENTRAL

Gravem 1981 {published data only}

Gravem A, Bugge A. Cis(Z)‐clopenthixol and clopenthixol in the treatment of acute psychoses and exacerbations of chronic psychoses. A double‐blind clinical investigation. Acta Psychiatrica Scandinavica Supplementum 1981;294:13‐24. [MEDLINE: 82178878; PMID 7041515]CENTRAL

Heikkila 1981 {published data only}

Heikkila L, Karsten D, Valli K. A double‐blind clinical investigation of cis(Z)‐clopenthixol and clopenthixol in chronic schizophrenic patients. Acta Psychiatrica Scandinavica Supplementum 1981;294:25‐9. [MEDLINE: 82178880; PMID 7041516]CENTRAL

Heikkila 1981a {published data only}

Heikkila L, Eliander H, Vartiainen H, Turunen M, Pedersen V. Zuclopenthixol and haloperidol in patients with acute psychotic states. A double‐blind, multicentre study. Current Medical Research and Opinion 1992;12(9):594‐603. [EMBASE 1992128093]CENTRAL
Heikkila L, Laitinen J, Vartiainen H. Cis(Z)‐clopenthixol and haloperidol in chronic schizophrenic patients ‐ a double‐blind clinical multicentre investigation. Acta Psychiatrica Scandinavica Supplementum 1981;294:30‐8. [MEDLINE: 82178881; PMID 7041517]CENTRAL

Huttunen1995 {published data only}

Huttunen MO, Piepponen T, Rantanen H, Larmo I, Nyholm R, Raitasuo V. Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double‐blind parallel‐group trial. Acta Psychiatrica Scandinavica 1995;91(4):271‐7. CENTRAL
Huttunen MO, Piepponen T. Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes. European Psychiatry 1994;9(Suppl 1):85. CENTRAL
Moller HJ, Huttunen MO. The prevalence of extrapyramidal symptoms during short and long term treatment with risperidone. 7th Biennial European Winter Workshop on Schizophrenia; 1994 Jan 23‐28; Les Diablerets, Switzerland 1994;11(2):106. [MEDLINE: 94001724; PMID 8104468]CENTRAL

Kingstone 1970 {published data only}

Kingstone E, Kolivakis T, Kossatz I. Double blind study of clopenthixol and chlorpromazine in acute hospitalized schizophrenics. Internationale Zeitschrift Fur Klinische Pharmakologie Therapie und Toxikologie 1970;3(1):41‐5. [MEDLINE: 70164847; PMID 4909377]CENTRAL

Kordas 1968 {published data only}

Kordas SK, Kazamias NG, Georgas JG, Papadokostakis JG. Clopenthixol: a controlled trial in chronic hospitalized schizophrenic patients. British Journal of Psychiatry 1968;114(512):833‐6. [MEDLINE: 68329665; PMID 4874163]CENTRAL

Mahadevan 1991 {published data only}

Mahadevan K, Gadhvi HM, Suri AK, Hussain MF, Sharma VK, Sharma SK, et al. A multicentre comparison of oral zuclopenthixol dihydrochloride and oral sulpiride in the treatment of acute schizophrenia. British Journal of Clinical Research 1991;2:13‐20. [Cochrane Library CN‐00282616]CENTRAL

Remvig 1987 {published data only}

Remvig J, Larsen H, Rask P, Skausig OB, Skov S, Stromgren LS. Zuclopenthixol and perphenazine in patients with acute psychotic states. A double‐blind multicentre study. Pharmacopsychiatry 1987;20(4):147‐54. [MEDLINE: 87290070; PMID 3615572]CENTRAL

Serafetinides 1972 {published data only}

Serafetinides EA. Consistency and similarity of drug EEG responses in chronic schizophrenic patients. International Pharmacopsychiatry 1973;8(4):214‐6. [MEDLINE: 74083340; PsycINFO 52‐05954; PMID 4589640]CENTRAL
Serafetinides EA. Voltage laterality in the EEG of psychiatric patients. Diseases of the Nervous System 1973;34(3):190‐1. [MEDLINE: 73210072; PsycINFO 1973‐29665‐001; PMID 4715636]CENTRAL
Serafetinides EA, Clark ML. Psychological effects of single dose antipsychotic medication. Biological Psychiatry 1973;7(3):263‐7. [MEDLINE: 74051947; PsycINFO 52‐03694; PMID 4586833]CENTRAL
Serafetinides EA, Collins S, Clark ML. Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Chemically unrelated antipsychotics as therapeutic alternatives. Journal of Nervous and Mental Disease 1972;154(1):31‐42. [MEDLINE: 72081124; PMID 4550211]CENTRAL
Serafetinides EA, Willis D. A method of quantifying EEG for psychopharmacological research. International Pharmacopsychiatry 1973;8(4):245‐7. CENTRAL
Serafetinides EA, Willis D, Clark ML. Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Journal of Nervous and Mental Disease 1972;155(5):366‐9. [MEDLINE: 73029970; PMID 4563078]CENTRAL

Wang 1995a {published data only}

Wang R. Double blind study of clopenthixsol treating schizophrenia. Medical Journal of Chinese Civil Administration1995; Vol. 7, issue 1:4‐5, 7. CENTRAL

References to studies excluded from this review

Aaes‐Jorgensen 1981a {published data only}

Aaes‐Jorgensen T. Serum concentrations of cis(Z)‐ and trans(E)‐clopenthixol after administration of cis(Z)‐clopenthixol and clopenthixol to human volunteers. Acta Psychiatrica Scandinavica Supplementum 1981;294:64‐9. [MEDLINE: 82178886; PMID 6951395]CENTRAL

Ahlfors 1980 {published data only}

Ahlfors UG, Dencker SJ, Gravem A, Remvig J. Clopenthixol decanoate and perphenazine enanthate in schizophrenic patients. A double‐blind Nordic multicentre trial. Acta Psychiatrica Scandinavica Supplementum 1980;279:77‐91. [MEDLINE: 80262296; PMID 6996426]CENTRAL

Al Haddad 1996 {published data only}

Al Haddad MK, Kamel C, Mawgood MA, Sequeria RP. Zuclopenthixol versus haloperidol in the initial treatment of schizophrenic psychoses,affective psychoses and paranoid states: a controlled clinical trial. Arab Journal of Psychiatry 1996;7(1):44‐54. [PsycINFO 2001‐16512‐004]CENTRAL

Arango 2002 {published data only}

Arango C, Bombýn I, Bobes´J, Gonzalez‐, Cabeza Garcýa‐, Salvador MT. Prediction and prevention of violence in schizophrenia outpatients: preliminary report. Schizophrenia Research 2002;53(3 Suppl.1):233. [MEDLINE: 2003183416]CENTRAL

Baastrup 1993 {published data only}

Baastrup PC, Alhfors UG, Bjerkenstedt L, Dencker SJ, Fensbo C, Gravem A, et al. A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis. Acta Psychiatrica Scandinavica 1993;37(1):48‐58. [MEDLINE: 93142586; PMID 8093824]CENTRAL

Bereen 1987 {published data only}

Bereen FJ, Harte FB, Maguire J, Singh AN. The use of oral zuclopenthixol in the treatment of functional psychotic illness. Pharmatherapeutica 1987;5(1):61‐8. CENTRAL

Bhattacharya 1987 {published data only}

Bhattacharya SN, Ghoshal J, Sharma SK, Halstead N, John B, Launer MA, et al. Acute functional psychoses:treatment with zuclopenthixol dihydrochloride ('Clopixol') tablets. Pharmatherapeutica 1987;5(1):1‐8. CENTRAL

Bobon 1989 {published data only}

Bobon D, de Bleeker E. Zuclopenthixol acetate and haloperidol in acute psychotic patients ‐ a randomized multicentre study. 2nd Congress of the European College of Neuropsychopharmacology; 1989 May 24‐26; Gothenburg, Germany. 1989. [MEDLINE: 76021805; PMID 240651]CENTRAL
Bobon D, de Bleeker E. Zuclopenthixol acetate and haloperidol in acute psychotic patients ‐ a randomized multicentre study. New Strategies in the Treatment of Aggressive, Acutely Psychotic Patients. Proceedings of the 8th World Congress of Psychiatry; 1989 October 13‐19, Athens, Greece. Excerpta Medica, 1989:47‐59. [MEDLINE: 76021805; PMID 240651]CENTRAL

Bourdouxhe 1987 {published data only}

Bourdouxhe S, Mirel J, Denys W, Bobon D. Zuclopenthixol acetate and haloperidol in acute psychoses ‐ results of the AMDP subgroup of a Belgian multicenter study [L'acetate de zuclopenthixol et l'haloperidol dans la psychose aigue ‐ Resultats du sous groupe AMDP d'une etude multicentrique belge]. Acta Psychiatrica Belgica 1987;87(2):236‐44. [MEDLINE: 87295330; PsycINFO 26‐73137; PMID 3618274]CENTRAL

Brook 1998 {published data only}

Brook S, Berk M, Selemani S, Kolloori J, Nzo I. A randomised controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis. 10th European College of Neuropsychopharmacology Congress; 1997 Sep 13‐17; Vienna, Austria. 1997. [MEDLINE: 95351128; PMID 7542829]CENTRAL
Brook S, Berk M, Selemani S, Kolloori J, Nzo I. A randomised controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis. Unpublished Report submitted to Human Psychopharmacology Clinical and Experimental1996. [MEDLINE: 95351128; PMID 7542829]CENTRAL
Brook S, Berk M, Selemani S, Kolloori J, Nzo I. A randomized controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis. Human Psychopharmacology 1998;13(1):17‐20. [EMBASE 1998035700]CENTRAL

Burke 2002 {published data only}

Burke JG, Reveley MA. Improved antisaccade performance with risperidone in schizophrenia. Journal of Neurology, Neurosurgery, and Psychiatry 2002;72:449‐54. CENTRAL

Chin 1998 {published data only}

Chin CN, Hamid AR, Philip G, Ramlee T, Mahmud M, Zulkifli G, et al. A double blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics. Medical Journal of Malaysia 1998;53(4):365‐71. [MEDLINE: 74083340; PsycINFO 52‐05954; PMID 4589640]CENTRAL

Chouinard 1991 {published data only}

Chouinard G, Safadi G, Beauclair L. A double‐blind controlled study of intramuscular zuclopenthixol acetate and liquid oral haloperidol in the treatment of schizophrenic patients with acute exacerbation. Journal of Clinical Psychopharmacology 1994;14(6):377‐84. [MEDLINE: 95190073; PMID 7884017]CENTRAL
Chouinard G, Safadi G, Beauclair L. The management of acutely schizophrenic patients newly admitted from the emergency room: a double‐blind clinical trial comparing zuclopenthixol acetate and liquid haloperidol. Modern Trends in the Treatment of Chronic Schizophrenia. Proceedings of a Symposium; 1991 June 10, Florence, Italy. Excerpta Medica, 1991:35‐43. [MEDLINE: 95190073; PMID 7884017]CENTRAL

Clark 1969 {published data only}

Clark. Sordinol versus chlorpromazine versus placebo. Psychopharmacology Bulletin 1969;3:54‐6. [01003]CENTRAL

CTRI‐2014‐07‐004712 {published data only}

CTRI‐2014‐07‐004712. Rapid tranquillization of violent or agitated patients in a psychiatric emergency setting: Pragmatic, randomized, allocation concealed, participant and assessor blinded trial of intramuscular zuclopenthixol acetate versus intramuscular haloperidol plus promethazine. Http://apps.who.int/trialsearch/Trial.aspx?TrialID=CTRI/2014/07/0047122014. CENTRAL
Mythri SV, Tharyan P, Sunder S, Kattula D, Kirubakaran R, Adams CE. Rapid tranquillization of violent or agitated patients in a psychiatric emergency setting: Pragmatic, randomized, allocation concealed, participant and assessor blinded trial of intramuscular zuclopenthixol acetate versus intramuscular haloperidol plus promethazine [A comparative study of the effects of an intramuscular injection of zuclopenthixol acetate versus an intramuscular injection of a combination of haloperidol plus promethazine in people with violence or agitation presenting to a psychiatric hospital as an emergency]. Study Protocol2013. CENTRAL

Den 2000 {published data only}

Den Boer JA, Vahlne JO, Post P, Heck AH, Daubenton F, Olbrich R. Ritanserin as add on medication to neuroleptic therapy for patients with chronic or subchronic schizophrenia. Human Psychopharmacology 2000;15(3):179‐89. [EMBASE 2000170004]CENTRAL

Dencker 1980 {published data only}

Dencker SJ, Lepp M, Malm U. Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double‐blind study of clopenthixol decanoate and flupenthixol palmitate. Acta Psychiatrica Scandinavica Supplementum 1980;279:10‐28. [MEDLINE: 80262290; PMID 6931470]CENTRAL
Dencker SJ, Malm U, Jorgensen A, Overo KF. Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. IV. Serum levels and clinical outcome. Acta Psychiatrica Scandinavica Supplementum 1980;279:55‐63. [MEDLINE: 80262294; PMID 6931473]CENTRAL

Dom 1978 {published data only}

Dom R, De Mesmaecker L, van den Broucke M, van Hest T, Baro F. Maintenance treatment of chronic schizophrenic patients. A study with the long‐acting thioxanthene derivative, cis(Z)‐clopenthixol decanoate‐sordinol depot. Acta Psychiatrica Scandinavica 1978;57(4):299‐304. [MEDLINE: 78207721; PMID 352094]CENTRAL

Fagerlund 2003 {published data only}

Fagerlund B, Mackeprang T, Gade A, Glenthoj BY. Effects of risperidone and zuclopenthixol on cognitive deficits in drug‐naive first episode schizophrenic patients. Schizophrenia Research 2003;60:133‐4. [CN‐00394142]CENTRAL

Fan 1999 {published data only}

Fan S, Sun ZG, Li J. The comparison of effects of clopenthixal and clozapine in the treatment of schizophrenia [氯噻噸與氯氮平治療精神分裂癥的效果比較]. Acta Acadimae Medicinae Qingdao1999; Vol. 35, issue 2:125‐7. CENTRAL

Fensbo 1990 {published data only}

Fensbo C. Zuclopenthixol acetate, haloperidol, and zuclopenthixol in the treatment of acutely psychotic patients ‐ A controlled multicenter study. Meeting of the Scandinavian Society for Psychopharmacology (1989, Copenhagen, Denmark) [Zuclopenthixol acetat, haloperidol og zuclopenthixol i behandling af akut psykotiske patienter. En kontrolleret multicenterundersogelse]. Nordisk Psykiatrisk Tidsskrift 1990;44(3):295‐7. [PsycINFO 28‐73892]CENTRAL

Fricchione 2010 {published data only}

Fricchione Parise V, Balletta G, Manna G. Risperidone depot versus zuclopenthixol depot for schizophrenia and schizophrenialike psychoses: Real world outcomes. European Neuropsychopharmacology2010; Vol. 1:472‐3. CENTRAL

Galdersi 1994 {published data only}

Galderisi S, Maj M, Mucci A, Bucci P, Kemali D. QEEG alpha1 changes after a single dose of high‐potency neuroleptics as a predictor of short‐term response to treatment in schizophrenic patients. Biological Psychiatry 1994;35(6):367‐74. [MEDLINE: 94289546; EMBASE 1994114037; PMID 8018782]CENTRAL

Glenthoj 2000 {published data only}

Glenthoj BY, Mackeprang T, Fagerlund B, Hemmingsen R. Effects of antipsychotics on information‐processing and extrastriatal dopamine d2/d3 receptors in first‐episode drug‐naive schizophrenic patients. 39th Annual Meeting of the American College of Neuropsychopharmacology; 2000; Dec 10‐14; San Juan; Puerto Rico. 2000:191. [MEDLINE: 95275743; PMID 7756183]CENTRAL
Glenth¢j BY, Mackeprang T, Fagerlund B, Hemmingsen RP. Effects of antipsychotic treatment on prepulse inhibition of the startle response (ppi) and cognition in first episode drug‐naive schizophrenic patients. Schizophrenia Research 2001;49(1,2):133. [PsycINFO 2001‐16512‐004]CENTRAL

Gravem 1990 {published data only}

Gravem A, Elgen K. Cis(Z) clopenthixol. The neuroleptically active isomer of clopenthixol. A presentation of five double blind clinical investigations and other studies with cis(Z) clopenthixol (Cisordinol(R), Clopixol(R)). Acta Psychiatrica Scandinavica, Supplementum 1981;64(294):5‐12. [MEDLINE: 82178884; PMID 6122337]CENTRAL
Gravem Arne, Tove AJ. Co‐injection of zuclopenthixol acetate and zuclopenthixol decanoate. Nordisk Psykiatrisk Tidsskrift 1990;44(4):403‐5. [PsycINFO 78‐07960]CENTRAL

Hicklin 1967 {published data only}

Hicklin A, Angst J. Retrospective and prospective studies on the clinical effect of clopenthixol (sordinol) in endogenous phychoses [Retrospektive und prospektive Studie uber die klinische Wirkung von Clopenthixol (Sordinol) bei endogenen Psychosen]. Schweizerische Medizinische Wochenschrift. Journal Suisse De Medecine 1967;97(19):615‐21. [MEDLINE: 69006168; PMID 5600894]CENTRAL

Hovens 2003 {published data only}

Hovens JEJM, Beijeman S, Tollenar J, Dries PJT, Loonen AJM. Risperidone versus zuclopenthixol in acute psychosis in emergency psychiatry: a prospective naturalistic study. Journal of the European College of Neuropsychopharmacology 2003;13(4):S293. CENTRAL

Hovens 2005 {published data only}

Hovens JE, Dries PJT, Melman CTM, Wapenaar RJC, Loonen AJM. Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open‐label study. Journal of Psychopharmacology2005; Vol. 19, issue 1:51‐7. [MEDLINE: 15671129]CENTRAL

Huang 2001 {published data only}

Huang SH, Pan YH, Wu FY, Qiu YP. Comparison of clopenthixol decanoate to chlorpromazine in the treatment of schizophrenia. Chinese General Practice 2001;4(10):775‐6. [CN‐00393723]CENTRAL

Karsten 1981 {published data only}

Karsten D, Kivimaki T, Linna SL, Pollari L, Turunen S. Neuroleptic treatment of oligophrenic patients. A double‐blind clinical multicentre trial of cis(Z)‐clopenthixol and haloperidol. Acta Psychiatrica Scandinavica Supplementum 1981;294(64):39‐45. [MEDLINE: 82178882; PMID 7041518]CENTRAL

Knegtering 2002a {published data only}

Knegtering H, Castelein S, Van Der Linde J, Bous J. Sexual dysfunctions and serum prolactin levels in patients using risperidone or quetiapine: a randomised trial. Schizophrenia Research 2002;53(3 Suppl 1):163. CENTRAL

Koskinen 1991 {published data only}

Koskinen T, Wistedt B, Thelander S. Zuclopenthixol decanoate vs haloperidol decanoate: a double‐blind comparative trial. 5th World Congress of Biological Psychiatry; 1991 Jun 9‐14; Florence, Italy. 1991:563‐5. [MEDLINE: 95275743; PMID 7756183]CENTRAL

Kristiansen 2001 {published data only}

Kristiansen KT, Mackeprang T, Fink‐Jensen A, Hemmingsen RP, Glenth¢j BY. Effects of antipsychotics and other agents on prepulse inhibition of the starlte response(ppi). Schizophrenia Research 2001;49(1,2):216. [PsycINFO 2001‐16512‐004]CENTRAL

Kristiansen 2003 {published data only}

Kristiansen KT, Mackeprang T, Glenthoj BY. Acute effects of antipsychotics and diazepam on prepulse inhibition of the startle response. Schizophrenia Research2003; Vol. 60, issue 1 Suppl 1:100. CENTRAL

Lamure 2003 {published data only}

Lamure M, Toumi M, Chabannes J‐P, Dansette G‐Y, Benyaya J, Hansen K. Zuclopenthixol versus haloperidol: an observational randomised pharmacoeconomic evaluation of patients with chronic schizophrenia exhibiting acute psychosis. International Journal of Psychiatry in Clinical Practice 2003;7(3):177‐85. CENTRAL

Lemmens 1994 {published data only}

Lemmens P, De Smedt G, Gheuens J, Tritsmans L. Efficacy of risperidone in the treatment of schizophrenia. Proceedings of the 7th Biennial Winter Workshop on Schizophrenia; 1994 Jan 23‐28; Les Diablerets, Switzerland1994; Vol. 11, issue 2:106. CENTRAL

Liu 1997b {published data only}

Liu P, Bian H, Chen H. Observation of clinical effect of clopixol‐acuphase injection for acute psychosis. Chinese Journal of Pharmaco Epidemiology [药物流行病学杂志]1997; Vol. 6, issue 4:202‐4. CENTRAL

Liu 1998a {published data only}

Liu S. A follow‐up of effects of sustain treatment of clopixol and cpz in schizophrenic patients. Sichuan Mental Health [四川精神卫生]1998; Vol. 11, issue 3:162‐3. CENTRAL

Loza 2001 {published data only}

Loza B, Kucharska‐Pietura K, Debowska G. Atypical versus typical antipsychotic treatment prognosis in first‐episode paranoid schizophrenia based on wcst and dichotic listening scores. European Neuropsychopharmacology (Abstracts of the 14th Congress of the European College of Neuropsychopharmacology; 2001 Oct 13‐17; Istanbul, Turkey) 2001;11(3):285. [14th Congress of the European College of Neuropsychopharmacology [Congress Information System]: Conifer, Excerpta Medica Medical Communications BV, 2001 P2103#]CENTRAL

Lublin 1991 {published data only}

Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, et al. Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. European Neuropsychopharmacology 1991;1(4):541‐8. [EMBASE 1998035700]CENTRAL

Mackeprang 2001 {published data only}

Mackeprang T, Fagerlund B, Videbaek C, Hemmingsen RP, Glenthoj BY. Extrastriatal dopamine(d2/d3)‐receptor occupancy and cognition in first episode schizophrenic patients. Schizophrenia Research 2001;49(Suppl.1,2):194. [LMD163341]CENTRAL

Malt 1995 {published data only}

Malt UF, Nystad R, Bache T, Noren O, Sjaastad M, Solberg KO, et al. Effectiveness of zuclopenthixol compared with haloperidol in the treatment of behavioural disturbances in learning disabled patients. British Journal of Psychiatry 1995;166(3):374‐7. [MEDLINE: 95307869; PMID 7788130]CENTRAL

Mann 1985 {published data only}

Mann BS, Moslehuddin KS, Owen RT, Clayton AR, Rohatgi KK, Sud P, et al. A clinical assessment of zuclopenthixol dihydrochloride ('Clopixol Tablets') in the treatment of psychotic illness. Pharmatherapeutica 1985;4(6):386392. CENTRAL

Martyns 1993 {published data only}

Martyns Yellowe IS. The decanoates of flupenthixol and clopenthixol in the treatment of chronic schizophrenic in‐patients. Implications for community psychiatry. West African Journal of Medicine 1993;12(2):110‐3. [MEDLINE: 94001724; PMID 8104468]CENTRAL
Martyns‐Yellowe IS. The positive and negative symptoms of schizophrenia: patterns of response to depot neuroleptic treatment. West African Journal of Medicine 1994;13(4):200‐3. [MEDLINE: 95275743; PMID 7756183]CENTRAL

Mazurek 2003 {published data only}

Mazurek I, Loza B, Lecyk A. Atypical versus typical antipsychotic treatment prognosis based on veps and wcst scores in paranoid schizophrenia. Journal of the European College of Neuropsychopharmacology 2003;13(4):S347. [P.2.156]CENTRAL

Meyers 1972 {published data only}

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References to other published versions of this review

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Aaes‐Jorgensen 1981

Methods

Allocation: randomised.
Blindness: double.
Duration: 1 week before cross‐over.
Design: cross‐over.
Country: Denmark.

Funding: Not mentioned.

Participants

Diagnosis: paranoid schizophrenia.
History: not clear in article but states duration of illness 2 months ‐ 2 years.
N = 9.
Age: mean 58 years, range 39‐81.
Sex: all male.
Inclusion criteria: all patients who had been previously treated with cis(Z)/trans(E)‐clopenthixol (from 2 months to several years).

Exclusion: not mentioned.
Setting: not reported.

Interventions

1. Cis(Z)‐clopenthixol hydrochloride: dose range 5 mg to 50 mg/day. Taken twice daily. N = 4.
2. Clopenthixol hydrochloride (cis(Z) and trans(E) forms): dose 10 mg to 100 mg/day. Taken twice daily. N = 5.

Outcomes

5.2 Leaving the study early for General Reasons (zero people left the study early).

Unable to use: Physiological ‐ serum concentrations of Cis(Z)‐clopenthixol and clopenthixol. Non‐clinical data all reported post‐cross‐over.

Notes

Cross‐over trial. Patient 4 excluded during statistical analysis (also received multiple drugs).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Done "in a randomised way". Authors do not state how.

Attempted to contact authors but Dikemark Hospital no longer exists.

Allocation concealment (selection bias)

Unclear risk

Authors do not comment.

Attempted to contact authors but Dikemark Hospital no longer exists.

Blinding

Low risk

Authors state "Double blindly".

Incomplete outcome data (attrition bias)
None

Low risk

None detected.

Selective reporting (reporting bias)

Low risk

All data appear to have been reported that was sought by the study's aims.

Other bias

High risk

Selection bias (n = 9) ‐ diagnostic purity bias.

Arango 2006

Methods

Allocation: randomised

Blindness: none ‐ open‐label

Duration: 1 year

Funding: Theodore and Vada Stanley Foundation Grant

Setting: 3 inpatient units

Participants

Diagnosis: schizophrenia

N = 46

Age: mean ˜34 years, range 24‐44

Sex: 38 male, 8 female

Inclusion:

DSM IV criteria for schizophrenia, a violent episode in the previous year with a score of greater than or equal to 3 on the physical aggression sub‐scale or the MOAS. A family member living with the patient and willing to collaborate with the researchers. Informed consent signed by the patient and the informant.

Exclusion:

Any other axis I disorders, including alcohol and/or drug abuse/dependence, mental retardation.

Interventions

1. Zuclopenthixol (oral) 35 mg/day n = 20

2. Zuclopenthixol (depot) 233 mg every 14 days (˜16.6 mg/day) n = 26

Additional medication: All received biperiden, other psychotropics were permitted.

Outcomes

Useable:

4. Mental State ‐ PANSS positive only

5. Leaving the study Early

7. Behaviour ‐ number of violent episodes

8. Adverse Effects ‐ additional medication

Unable to use:

7. Behaviour ‐ MOAS, baseline data only

8. Adverse effects ‐ UKU ‐ no data provided by group

Notes

Madrid

Inclusion criteria do not match included data and significant selective reporting.

Authors will need to be contacted at next update to obtain clarification.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

A researcher at one centre did the randomisation.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding

High risk

Open‐label.

Incomplete outcome data (attrition bias)
None

High risk

Missing UKU, missing PANSS.

Selective reporting (reporting bias)

High risk

MOAS not reported other than at baseline.

Other bias

High risk

Selection bias ‐ Berkson

Balasubramanian 1991

Methods

Allocation: randomised.
Blindness: double.
Duration: 10 weeks.
Design: outpatient and Inpatient
Country: UK.

Participants

Diagnosis: acute functional psychosis (schizophrenia n = 68, schizoaffective n = 7, hypomania n = 4, unknown n = 4 and unreported n = 11.
History: acutely ill / exacerbation of chronic illness, 0‐20 episodes.
N = 94.
Age: mean ˜ 36.9 years, range 18‐65. Age of one patient not recorded.
Sex: 48 male, 34 female, 13 unspecified (12 patients not analysed by authors and sex not reported in 1 patient). Lundbeck UK contacted to request information.
Inclusion criteria: BPRS 15 or more.
Exclusion criteria: previous intolerance to neuroleptics, additional serious psychiatric or neurological disorder, serious physical illness, pregnant or lactating women and those of child‐bearing potential who intend to become pregnant, addiction to drugs or alcohol, depot neuroleptic at an unstable dose or dosing frequency.
Setting: hospital and community.

Interventions

1. Zuclopenthixol: dose range 25 mg to 150 mg/day. N = 50.
2. Chlorpromazine: dose range 100 mg to 600 mg/day. N = 44.

Additional medication: amitriptyline, temazepam, procyclidine.

Outcomes

2. Global state: CGI.

Table 1

5. Leaving the study early.

Zuclo n = 32 completed study, Chlor n = 21 completed the study.
8. Adverse effects.

Table 1

Unable to use:
Mental state: BPRS (> 50% loss to follow‐up in one group).
Adverse effects: UKU side effects rating scale (data not reported by group).

Notes

Zuclopenthixol group previous episodes 0‐17. Chlorpromazine group previous episodes 0‐20.

Most common zuclopenthixol dose 75 mg/day.

Most common chlorpromazine dose 600 mg/day

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Authors do not mention. Lundbeck UK contacted to request information regarding potential biases 5th January 2016.

Allocation concealment (selection bias)

Unclear risk

Authors do not mention.

Blinding

Low risk

Clearly stated in the paper as double‐blind design.

Incomplete outcome data (attrition bias)
None

High risk

11 patients were excluded and not analysed. Missing outcome data.

Selective reporting (reporting bias)

Low risk

All data appear to have been reported on.

Other bias

High risk

Attrition bias ‐ per protocol analysis.

Ban 1975

Methods

Allocation: randomised.
Blindness: double.
Duration: 12 weeks.
Design: single‐centre.
Country: Canada.

Funding: Public health service research grant ‐ Pfizer

Participants

Diagnosis: schizophrenia.
N = 30.
Age: mean 37 years, range 18‐58.
Sex: 13 male, 17 female.
Inclusion: diagnosis of schizophrenia

Exclusion criteria: not reported.
Setting: hospital.

Interventions

1. Clopenthixol: dose range 50 mg to 200 mg/day. Average 150 mg/day. N = 10.
2. Thiothixene: dose range 10 mg to 40 mg/day. average 30 mg/day. N = 10.
3. Chlorprothixene: dose range 150 mg to 600 mg/day. Average 450 mg/day. N = 10.

Outcomes

Useable:

2. Global state: CGI.

5. Leaving the study early
8. Adverse effects: number of adverse effects in every group, partial TESS

Unable to use:
4. Mental state: BPRS (data not reported by group).
7. Behaviour: NOSIE (no data available).
8. Adverse effects: TESS (no data available).

Notes

15 chronic and 15 new admissions. Original Cochrane authors did not include the two‐week washout period in the duration of the study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Suggested but not reported by authors. "10 week double blind."

Allocation concealment (selection bias)

Unclear risk

Not mentioned.

Blinding

Low risk

"10 week double blind."

Incomplete outcome data (attrition bias)
None

Low risk

None obvious and none mentioned by authors.

Selective reporting (reporting bias)

High risk

Multiple areas where data not reported.

Several papers produced with same data.

Other bias

High risk

Selection bias ‐ sampling ‐ Berkson

CSzG Study ID 9828 2005

Methods

Allocation: inpatient

Blindness: randomised by specially assigned person

Duraton:: 6 weeks

Participants

Diagnosis: CCMD ‐ 3

N = 120

Age: mean ˜33 years, range 24‐42

Exclusion: severe physical diseases, alcohol and substance dependence

Interventions

1. Clopenthixol 40 mg to 70 mg/day. N = 60

2. Chlorpromazine 300 mg to 550 mg/day. N = 60

Other antipsychotics were not allowed during the treatment.

Benzhexol and diazepam were used if necessary.

Outcomes

Able to use:

4. Mental state: BPRS, PANSS

8. Adverse Effects: EPSEs and excessive sedation

Unable to use:

4. Mentals State: SANS ‐ no useable data

Notes

Paper kindly translated and data extracted by Jun Xia.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Not mentioned. No detailed information was described in the study. No Concerns raised by the data extractor.

Allocation concealment (selection bias)

Low risk

Not mentioned. No detailed information was described in the study. No Concerns raised by the data extractor.

Blinding

Low risk

Randomised. No detailed information was described in the study. No Concerns raised by the data extractor.

Incomplete outcome data (attrition bias)
None

Low risk

All outcomes reported.

Selective reporting (reporting bias)

Low risk

None found.

Other bias

Low risk

None obvious.

Dehnel 1968

Methods

Allocation: randomised.
Blindness: double.
Duration: 13 weeks.
Design: single centre.
Country: USA.

Funding: Not reported.

Participants

Diagnosis: chronic schizophrenia.
History: hospitalised patients with schizophrenia with duration of illness 2 months‐to 3 years.
N = 50.
Age: mean ˜ 43 years, range 25‐59.
Sex: all male.
Inclusion criteria: patients under 60 years of age and free of significant physical illness such as liver disease or severe cardiovascular disease.

Exclusion criteria: not discussed.
Setting: not reported.

Interventions

1. Clopenthixol: dose 132.5 mg/day, range 25 mg to 250 mg/day. N = 25.
2. Perphenazine: dose 51.2 mg/day, range 8 mg to 80 mg/day. N = 25.

Outcomes

Useable:

2. Global state: CGI.

5. Leaving the study early.
8. Adverse effects: requiring additional medication ‐ benztropine methanesulphate; other medications.

Unable to use:
4. Mental state: BPRS (no SD), PIP (no data by group).

8. Adverse Effects ‐ table 3 ‐ week 12 missing

Notes

All but two patients were taking 1 or more psychoactive drugs (mostly phenothiazines) before starting the study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported, suggested but not clear.

Allocation concealment (selection bias)

Unclear risk

Not reported, suggested but not clear.

Blinding

Low risk

Reasonable methods employed for blinding.

Incomplete outcome data (attrition bias)
None

Low risk

Reasons given by authors.

Selective reporting (reporting bias)

Low risk

Not detected.

Other bias

High risk

Per‐protocol analysis.

Fagerlund 2004

Methods

Allocation: Random

Blindness: open‐label

Duration: 13 weeks

Funding: Danish Medical Counscil, H:S Research council, University of Copenhagen Faculty of Humanities

Location: Copenhagen

Participants

Diagnosis: ICD10 F20 Schizophrenia

N = 31

Age: 27.3 years (+/‐5.9), range 19‐37

Sex: not discussed

History: untreated psychosis 4‐78 months

Inclusion: anti‐psychotic naive admitted for treatment and written informed consent

Exclusion: known retardation, need acute medication, compulsorily hospitalised

Interventions

1. Zuclopenthixol 6 mg to 26 mg average 9.6 mg. N = 10

2. Risperidone 2 mg to 7 mg average 3.6 mg. N = 15

3: Healthy controls N = 25

Additional Medication: Benzodiazepiens and anticholinergics but not on the day of examination

Outcomes

Usable:

4. Mental State: PANSS ‐ table 2

5. Leaving the study Early

Not Useable:

6. General Functioning: Cognitive Functions (CANTAB, WCST, verbal fluency, Figural fluency, trail making tests A & B, DART) ‐ no useable data

8. Adverse Effects: ESRS ‐ no data

Notes

Not all data published by authors. When review next updated the authors should be contacted to obtain this information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Stated but not elaborated on.

Allocation concealment (selection bias)

High risk

Open‐label.

Blinding

High risk

Open‐label.

Incomplete outcome data (attrition bias)
None

Unclear risk

Authors state they will publish other data elsewhere though not found in searches to date.

Selective reporting (reporting bias)

Unclear risk

Authors state they will publish other data elsewhere though not found in searches to date.

Other bias

High risk

Selection bias, Berkson

Fischer‐Cornelssen 1976

Methods

Allocation: randomised not clear.
Blindness: double.
Duration: 7 weeks.
Design: multicentre.
Country: Switzerland.

Funding: not stated

Participants

Diagnosis: acute paranoid schizophrenia.
History: moderate to severe hospitalised acute patients with schizophrenia.
N = 723.
Age: not reported.
Sex: not reported.
Inclusion criteria: moderate to severe acute patients with schizophrenia.
Setting: hospital.

Interventions

1. Clopenthixol: dose 100 mg/day. N = 36.
2. Clozapine: dose 200 mg to 300 mg/day. N = 371.
3. Chlorpromazine: dose 200 mg to 350 mg/day. N = 212.
4. Haloperidol: dose 4 mg to 8 mg/day. N = 78.
5. Trifluoperazine: dose 20 mg to 30 mg/day. N = 36.

Outcomes

Useable:

8. Adverse effects: drowsiness, stimulation, confusion, gastrointestinal side‐effects, anticholinergic side‐effects, dizziness, orthostatic reaction, headache, hypersalivation, hypokinesia, hyperkinesia, dyskinesia, rigor, tremor, akathisia.

Unable to use:
2. Global state: number of patients completing the study not provided.
4. Mental state: BPRS (no clear data).

Notes

All of the higher dose ranges are medians.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported. Sandoz UK contacted by online form to clarify bases and seek additional data 5th January 2016.

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding

Unclear risk

Authors state double‐blind but do not say how.

Incomplete outcome data (attrition bias)
None

Unclear risk

Total figures are not provided.

Selective reporting (reporting bias)

High risk

Sandoz side‐effect check list not reported.

Other bias

High risk

Selection bias, performance bias, unclear if intention‐to‐treat analysis was used.

Glenthoj 2007

Methods

Allocation: random

Blindness: not reported

Duration: 12 weeks

Funding: committee on medicine and science ‐ personal grant and an undisclosed non‐restricted grant

Participants

Diagnosis: F20 schizophrenia

n = 45

Age: ˜21‐33 years

Sex: 25 male, 13 female, 7 unknown

Included: drug naive first episode patients with schizophrenia, F20 ICD10 criteria for schizophrenia

Excluded: mental retardation, severe somatic diseases, severe head trauma, pregnancy, presence of MRI contraindications, acute need of medication, compulsory hospitalisation in patients, presence of psychotic illness in controls or their first‐degree relatives.

Interventions

1. Zuclopenthixol (n = 8) 10.3 mg/day average (3.8 mg to 16.8 mg)

2. Risperidone (n = 11) 3.4 mg/day average (1.9 mg to 4.9 mg)

3. Control (n = 20)

Of the original n = 45 it is unclear as to which groups the remaining n = 6 were attributed.

Other medication: Anticholinergic n = 1‐, antidepressant n = 1, benzodiazepines n = 11

Outcomes

Usable:

4. Mental State: PANSS ‐ table 2 (PANSS general, mean and SD baseline and follow‐up).

5. Leaving the study early

8: Adverse effects ‐ ESRS ‐ table 2

Notes

3 patients minimally medicated prior to the start of the study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Not reported. DRCMR research group contacted 5th January 2016 to clarify these biases and seek any missing information.

Allocation concealment (selection bias)

High risk

Not reported.

Blinding

High risk

Not reported.

Incomplete outcome data (attrition bias)
None

High risk

Conflicting reports from several papers using same population cohort.

Selective reporting (reporting bias)

High risk

Supplementary publications highlight dropout and inconsistencies in the randomisation.

Other bias

High risk

Berkson bias

Gravem 1978

Methods

Allocation: unclear. "In the investigation patients ... were allocated." Implied when table 1 reviewed.
Blindness: double.
Duration: 4 weeks
Design: RCT
Country: Norway

Participants

Diagnosis: acute and chronic psychoses, mainly schizophrenia
N = 20
Age: 20‐66 years (mean 36)
Sex: 13 male, 7 female
Inclusion criteria: acute psychoses and chronic exacerbations.

Exclusion: below 15 years age, serious somatic disease, pathological laboratory findings, pregnant patients.
Setting: Inpatient

Interventions

1. Cis(Z)‐clopenthixol 48mg/day range 10 mg to 150 mg/day. N = 10.
2. Cis(Z)/trans(E) ‐ clopenthixol 88 mg/day range 10 mg to 200 mg/day. N = 10.

Outcomes

2. 6 Average Endpoint in global state scores

Table 7, CGI

5. Leaving the study early n = 2, (one for refusal due to side‐effects, oculogyric crisis and one for non‐compliance)

Unable to use:
Physiological: serum concentrations of Cis(Z)‐clopenthixol and clopenthixol (non‐clinical data all reported post‐cross‐over).

4. 4 Average endpoint general mental state score

Table 3 and 4 ‐ CGI time 0, 2 weeks and 4 weeks no SD

4. 4 Average change in general mental state scores

Table 5 ‐ BPRS ‐ total score time 0, 2 weeks and 4 weeks. no SD

4. 8 Average change in specific symptom scores

Thinking disturbance: Table 5 ‐ BPRS ‐ time 0, 2 weeks and 4 weeks. no SD

4. 8 Average change in specific symptom scores

Withdrawal ‐ retardation: Table 5 ‐ BPRS ‐ time 0, 2 weeks and 4 weeks. noS.D

4. 8 Average change in specific symptom scores

Hostile‐suspiciousness: Table 5 ‐ BPRS ‐ time 0, 2 weeks and 4 weeks. no SD

4. 8 Average change in specific symptom scores

Anxious‐depression: Table 5 ‐ BPRS ‐ time 0, 2 weeks and 4 weeks. no SD

8. 1 Clinically important general adverse effects

Table 8, individual side‐effects and totals. Frequencies not patient numbers.

Notes

none

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported but implied; "A double blind clinical investigation".

Allocation concealment (selection bias)

Unclear risk

patients were "allocated"

Attempted to contact authors but Dikemark Hospital no longer exists. Google search did not reveal any contact details of the authors.

Blinding

Low risk

Authors state double‐blinding but the details are not clear in the paper.

Incomplete outcome data (attrition bias)
None

Low risk

The two excluded patients had reasons given by the authors.

Selective reporting (reporting bias)

Low risk

Reported all outcomes stated in the study aims.

Other bias

Unclear risk

Berkson and diagnostic purity bias.

Gravem 1981

Methods

Allocation: patients are allocated to each group and it is unclear if a process of randomisation occurred. A review of table one suggests an element of randomisation ‐ implied randomisation.
Blindness: double.
Duration: 8 weeks.
Design: cross‐over.
Country: Denmark.

Funding: not declared.

Participants

Diagnosis: chronic schizophrenia.
History: illness duration 5‐20 years
N = 57
Age: mean ˜50 years, range 24‐79
Sex: 53 male and 4 female
Inclusion criteria: chronic patients already in neuroleptic treatment, preferably clopenthixol

Exclusion: not mentioned
Setting: inpatient

Interventions

1. Cis(Z)‐clopenthixol hydrochloride, n = 29 average dose 47.6 mg/day
2. Clopenthixol hydrochloride (cis(Z) and trans(E) forms), n = 28 average dose 150 mg/day

Table 2 dosing reported by authors is unclear.

Outcomes

2.6 Global State ‐ Average change in global state scores (Table 1)

4.3 Average endpoint general mental state score

5.2 Leaving the study early (for general reasons) ‐ zero people left the study

6.3 General Functioning ‐ average endpoint general functioning scores (Table 4)

Unable to use: Physiological ‐ serum concentrations of Cis(Z)‐clopenthixol and clopenthixol (non‐clinical data all reported post‐cross‐over).

Notes

none.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported but implied; "A double blind clinical investigation".

Allocation concealment (selection bias)

Unclear risk

Not reported.

Blinding

Low risk

Stated in paper. "The drugs were given double blindly in a randomised way."

Incomplete outcome data (attrition bias)
None

Low risk

No incomplete outcome data.

Selective reporting (reporting bias)

Low risk

None noted.

Other bias

Unclear risk

Berkson and diagnostic purity bias.

Heikkila 1981

Methods

Allocation: "The patients were allocated..." Implied randomisation.
Blindness: double.
Duration: 8 weeks
Design: RCT
Country: Finland

Funding: not stated

Participants

Diagnosis: 40 patients with schizophrenia and 14 patients with oligophrenia.
History: vast majority ill or hospitalised more than 5 years.
N = 54
Age: Mean ˜45 years
Sex: 28 male, 26 female
Inclusion/exclusion: not reported
Setting: not reported.

Interventions

1. Cis(Z)‐clopenthixol 73 mg/day (10 mg to 150 mg/day). N = 26
2. Cis(Z)/Trans(E)‐clopenthixol 114 mg/day (20 mg to 300 mg/day). N = 28

Outcomes

2. 5 Average endpoint global state score

Table 3 and 5: Severity of illness, scale unclear

5. Leaving the study early

Table 3 and 5: n = 5 left, reasons not stated in the article.

8. 3 Average endpoint general adverse effect score

Table 7: Single side‐effects week 8 total

Unable to use:

8. 4 Average change in general adverse effect scores

Table 6: Side‐effects interfering with patient's functioning ‐ CGI. No SD.

8. 8 Average change in specific adverse effects

Table 7: Single side‐effects. No SD.
Physiological: serum concentrations of Cis(Z)‐clopenthixol and clopenthixol (non‐clinical data all reported post‐cross‐over).

Notes

none

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported ‐ Finland Central Hospital contacted by email 5th January 2016.

Allocation concealment (selection bias)

Unclear risk

Not reported ‐ Finland Central Hospital contacted by email 5th January 2016.

Blinding

Unclear risk

Reported but not detailed

Incomplete outcome data (attrition bias)
None

High risk

At week 8, five patients were not included in the outcome data and not accounted for by the authors.

Selective reporting (reporting bias)

Unclear risk

Not enough information to make a clear decision.

Other bias

Low risk

Per protocol analysis, attrition bias

Heikkila 1981a

Methods

Allocation: not stated
Blindness: double, implied randomisation
Duration: 12 weeks.
Design: multicentre.
Country: Finland.

Funding: Not stated

Participants

Diagnosis: chronic schizophrenia (n = 58) or other psychotic (n = 5, paranoic state, depressive/PD)
History: n = 40 duration of illness > 10 years and n = 11 for > five years.
N = 63.
Age: mean ˜ 43 years.
Sex: 41 male, 22 female.
Inclusion criteria: chronic schizophrenic inpatients or other psychotic inpatients who might benefit from either of these drugs or already receiving such treatment.
Exclusion criteria: patients under 15 years of age, with serious concomitant somatic illness or pathological laboratory findings, and pregnant patients.
Setting: hospitalised.

Interventions

1. Cis(Z)‐zuclopenthixol: dose 40 mg/day. N = 30.
2. Haloperidol: dose 10 mg/day. N = 33.

Outcomes

Useable:

2. Global state: CGI.

5. Leaving the study early [n = 27 left (13 Zuclo and 14 Halo) ‐ only 13 accounted for: n = 1 discharge, n = 9 insufficient effect and side‐effects, n = 3 reasons unrelated to treatment]
8. Adverse effects: use of other therapeutic drugs. CGI, frequency only.

Unable to use ‐
2. Global State: NOSIE 30 (unable to use data). CGI ‐ percentages only
4. Mental state: BPRS (no SD).

Notes

Previous neuroleptic medication: 14 different neuroleptics.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated. Hospital District of South West Finland contacted to seek further information on biases 5th January 2016.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding

Low risk

Double‐blind.

Incomplete outcome data (attrition bias)
None

High risk

27 patients dropped out and only 12 accounted for by the authors.

Selective reporting (reporting bias)

Unclear risk

Not able to ascertain from paper.

Other bias

High risk

Berkson bias, diagnostic purity bias

Huttunen1995

Methods

Allocation: randomised.
Blindness: double.
Duration: 6 weeks.
Design: multicentre.
Country: Finland.

Funding: not stated

Participants

Diagnosis: chronic schizophrenia or schizophreniform disorder with an acute exacerbation (DSM‐III‐R).
History: community patients with acute exacerbation of chronic schizophrenia.

N = 98.
Age: mean ˜ 47 years, range 18‐65.
Sex: 47 male, 51 female.

Inclusion criteria: acute exacerbations. 18‐65y, acute psychotic symptoms necessitating antipsychotic treatment. Diagnosis of chronic or sub‐chronic schizophrenia or schizophreniform disorder according to DSM III‐R

Exclusion criteria: patients with clinically significant organic or neurological disorder, serious psychotic disorder other than schizophrenia or schizophreniform disorder, clinically relevant abnormalities in laboratory tests, patients likely to be noncompliant, as well as pregnant or lactating women and those of reproductive age without adequate contraception.

Setting: community.

Interventions

1. Zuclopenthixol: dose 38 mg/day, range 10 mg to 100 mg/day. N = 50.
2. Risperidone: dose 8 mg/day, range 2 mg to 20 mg/day. N = 48.

Authors aimed to avoid anti‐parkinsonism medication and benzodiazepines.

Outcomes

Useable:

5. Leaving the study early (n = 98 to n = 40)

8. Adverse effects: use of antiparkinsonian medication.

8. Adverse effects: UKU side effect rating scale

Unable to use

1. Death: n = 1 patient on risperidone. died 1 month after the trial. This patient was only on the drug for one week and the pathology diagnosis was viral myocarditis. The authors deemed this to not be related to risperidone.

4. Mental state: PANSS score, BPRS (originally included but upon review data is unusable)
Vital signs, body weight, laboratory screening (no data by group).

8. Adverse effects: extrapyramidal symptom rating scale (data not useable)

Notes

Discontinuation of anti‐parkinsonism and other psychotropic medication.

Author contacted to seek clarification of some data: no reply at the time of writing. Information from multiple papers.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised but not stated how. E‐mailed M.O Huttunen Summer 2015 with no response to date.

Allocation concealment (selection bias)

Unclear risk

Randomised but not stated how. E‐mailed M.O Huttunen Summer 2015 with no response to date.

Blinding

Unclear risk

Mentioned but not clear how. E‐mailed M.O Huttunen Summer 2015 with no response to date.

Incomplete outcome data (attrition bias)
None

Low risk

Intention‐to‐treat analysis

Selective reporting (reporting bias)

High risk

Report mean for non‐normal data instead of median. Only reported CGI data on comparison to previous neuroleptic treatment.

Other bias

High risk

Diagnostic purity and attrition biases.

Kingstone 1970

Methods

Allocation: randomised.
Blindness: double.
Duration: 3 weeks.

Funding: Ayerst, McKenna and Harrison LTD

Participants

Diagnosis: schizophrenic reaction (different subtypes) plus one extreme incapacitating anxiety in a schizoid personality.

N = 41

Age: 18‐65 years, mean ˜31 years

Sex: 16 male, 25 female

History:

Duration of illness 0.4 ‐ 5.3 years

Included: acute psychotic symptomatology

Excluded: not mentioned.

Interventions

1. Clopenthixol (N = 20) 122 mg/day (75 mg to 600 mg), n = 5 additional medication

2. Chlorpromazine (N = 21) 435 mg/day (150 mg to 1800 mg), n = 2 additional medication

All patients had previous treatment.

Outcomes

Used:

2. Global state ‐ Global assessment ‐ table 2

4. Mental state ‐ BPRS ‐ table 1

5. Leaving the study early n = 4 (Chlorpromazine, 1 exhausted tablets and 3 due to side‐effects). n = 1 (zuclopenthixol, side‐effects).

8. Adverse effects ‐ table 3 and additional medication n = 7 (authors do not mention which additional medication)

Unable to use:

5. Leaving the study early

"Several patients ... diagnosis changed ... to a non‐psychotic disorder or to a brain syndrome were dropped from the study." No data.

Notes

none.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Implied randomisation.

Response: Patients assigned a number belonging to a bottle of medications.

Research unit at the Royal Victoria Hospital in Quebec contacted for more information on biases and missing patient information 5th January 2016.

Allocation concealment (selection bias)

Low risk

Contents of bottles not known to anyone in the study until the end.

Blinding

Low risk

Study states "double blind".

Incomplete outcome data (attrition bias)
None

High risk

Several patients not included in the study because of a change in diagnosis. The numbers were not given and not included in the analysis.

Selective reporting (reporting bias)

High risk

Missing data, areas not reported but alluded to in discussion.

Other bias

High risk

Berkson bias, attrition bias, per protocol analysis

Kordas 1968

Methods

Allocation: "Patients were subsequently allocated" ‐ randomisation implied
Blindness: single (patient)
Duration: 6 weeks.
Design: single centre.
Country: Greece.

Participants

Diagnosis: chronic schizophrenia.
History: duration of illness 6 years and over.
N = 54.
Age: mean ˜43 years, range 26‐64.
Sex: 29 male, 25 female.
Inclusion: established diagnosis of schizophrenia in hospital records

Exclusion criteria: not reported.
setting: hospital.

Interventions

1. Clopenthixol: dose 150 mg/day. N = 18.
2. Chlorpromazine: dose 300 mg/day. N = 18.
3. Placebo. N = 18.

Additional Medication: Artane and Phenergan.

Outcomes

Used:

5. Leaving the study early n = 0

8. Adverse effects: number of patients experiencing side‐effects.

(all on clopenthixol, n = 3 restarted menstruation, n = 2 parkinsonism, n = 1 oculogyric crisis

Not used:

7. Behaviour: behavioural scale, Aof V (table III) ‐ no usable data

Notes

none

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not mentioned. Contacted Dromokaītion Hospital Athens to obtain further information on bias 5th January 2016.

Allocation concealment (selection bias)

Unclear risk

"...patients were subsequently allocated into three groups..." Unclear how.

Blinding

Unclear risk

"He was the only person knowing the identity of the tablets and to which group the patients belonged." Unclear if single‐ or double‐blind.

Incomplete outcome data (attrition bias)
None

Unclear risk

First rating deleted from analysis as was considered to be training by the researchers.

Selective reporting (reporting bias)

High risk

See above

Other bias

High risk

Hospitalised patients used ‐ Berkson bias.

Mahadevan 1991

Methods

Allocation: randomised.
Blindness: single.
Duration: 10 weeks.
Design: multicentre.
Country: UK.

Funding: not declared.

Participants

Diagnosis: acute schizophrenia (RDC).
N = 61.
Age: mean ˜ 39 years, range 18‐65.
Sex: 26 male, 35 female.

Inclusion criteria: aged 18‐65 years inclusive, were experiencing an acute schizophrenic episode according to RDC and minimum BPRS score of 15.

Exclusion criteria: concurrent serious physical illness, patients who had previously demonstrated intolerance to neuroleptics, received a depot neuroleptic in the previous 2 weeks, or were suffering from a serious additional psychiatric or neurological disorder, patients who were pregnant or lactating; dependence or addiction to drugs or alcohol.

Setting: hospital.

Interventions

1. Zuclopenthixol dihydrochloride: dose range 25 mg to 150 mg/day. N = 30.
2. Sulpiride: dose 200 mg to 1200 mg/day. N = 31.

Additional medication: temazepam (insomnia), procyclidine (EPSEs), amitriptyline (depression).

Outcomes

usable:

2. Global state: CGI.
4. Mental state: BPRS.

5. Leaving the study Early
8. Adverse effects: change in mean weight.

Notes

Multicentre

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomised but not elaborated on by authors. Bolton General Hospital contacted 5th January 2016 to seek clarification from the first author regarding biases.

Allocation concealment (selection bias)

Low risk

Randomly allocated but not elaborated on.

Blinding

Low risk

Clearly stated.

Incomplete outcome data (attrition bias)
None

Low risk

Authors discuss

Selective reporting (reporting bias)

High risk

Not all data was reported in the paper.

Other bias

High risk

Diagnostic purity bias, attrition bias, per‐protocol analysis

Remvig 1987

Methods

Randomised, double‐blind, 12 weeks

Participants

Acute psychosis

N = 54

Age: 20‐60 years (mean 38)

Sex: 25 female, 15 male, 14 unspecified

Inclusion: hospitalised in the preceding 7 days, acute psychosis, exacerbation of chronic psychosis, neuroleptic treatment was anticipated to be at least 3 weeks, informed consent.

Excluded: mania/depression, serious somatic disease, organic brain damage, pregnant, history of abuse, previous good response to neuroleptic

Interventions

1. Zuclopenthixol 37 mg/day (10 mg to 20 mg) n = 27

2. Perphenazine 30 mg/day (8 mg to 72 mg) n = 27

Additional medication: benzodiazepines, methotrimeprazine, anti‐parkinsonism medication

Outcomes

5. Leaving the study early

Unable to use:

2. Global state: CGI

4. Mental state: CPRS

8 Adverse effects

Notes

Multicentre

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated. Glostrup hospital contacted 5th January 2016 to obtain further information to clarify biases and seek additional outcome data if available.

Allocation concealment (selection bias)

Unclear risk

Not stated.

Blinding

Low risk

Double‐blind stated.

Incomplete outcome data (attrition bias)
None

Low risk

Not detected.

Selective reporting (reporting bias)

High risk

Multiple data not reported and often unclear.

Other bias

High risk

Berkson bias evident.

Serafetinides 1972

Methods

Allocation: randomised.
Blindness: double.
Duration: 24 weeks.
Design: single centre.
Country: USA.

Funding: United states Public health service grant

Participants

Diagnosis: chronic schizophrenia.
History: duration of illness 2 years or longer.
N = 57.
Age: mean ˜ 42 years, range 21‐61 years.
Sex: 25 male, 32 female.
Inclusion criteria: no evidence of organic disease, duration of illness 2 years or longer, chronic schizophrenia, permission from a family member

Exclusion: no complicating organic illness or known brain damage
Setting: hospital.

Interventions

1. Clopenthixol: dose 205 mg/day. N = 15.
2. Haloperidol: dose 12.3 mg/day. N = 14.
3. Chlorpromazine: dose 830 mg/day. N = 14.
4. Placebo. N = 13.

Additional medication: antiparkinsonian medication, sedative.

Outcomes

Useable:

5. Leaving the study early: n = 4 (behavioural deterioration n = 2, 1 Chlorpromazine and 1 placebo, Intestinal obstruction secondary faecal impaction n = 2, both chlorpromazine)
8. Adverse effects ‐ table 10 and 11

Unable to use ‐
2. Global state: CGI (no SD)

4. Mental state: BPRS (no SD).

Short‐term data not reported (first 12 weeks medication free)

Notes

Originally reported as a 12‐week study in previous review.

Combination of several papers (6 in total) all reporting on the same cohort.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"In a double blind placebo controlled trial..."

Implied but not clear.

Allocation concealment (selection bias)

High risk

Not specifically discussed by the authors but "subjects were housed together on a special two‐wing ward, males in one wing and females in the other" so it is unlikely that allocation concealment was maintained.

Blinding

Low risk

Authors state double‐blind. Not discussed how.

Incomplete outcome data (attrition bias)
None

Unclear risk

Incomplete data described by the authors but not used in outcome data.

Selective reporting (reporting bias)

High risk

Multiple papers, same patient cohort.

Other bias

High risk

Selection bias (Berkson), Suspected data mining, likely per‐protocol analysis.

Wang 1995a

Methods

Allocation: Quote” Patients were randomly divided into two groups ”(p.4)

Blinding: Double‐blind

Duration: Quote”8 weeks”(p. 4)
Location: Quote ”Inpatients, WuHan, China” (p.4)

Participants

Schizophrenia, CCMD‐3;
Sex: male 31 female 29
Age:mean˜34.1 years, SD ˜12.5
Total N = 64

Inclusion and exclusion criteria:
Patients with schizophrenia fulfilled CCMD‐3 were included;
Patients with severe heart, liver, kidney diseases were excluded.

Interventions

1. Zuclopenthixol Group: (n = 33)
Management: newly hospitalised patients had to stop the previous drugs for three days and then were randomly divided into Zuclopenthixol Group or Chlorpromazine Group.
Chlorpromazine or Zuclopenthixol was enclosed in the same colour, style capsule by pharmacist.
In the first week of treatment, the dosage of Zuclopenthixol was 20 mg/day and from the second week, it was increased 10 mg/day every week.
No other antipsychotic drugs were allowed during the treatment.
Trihexyphenidyl or scopolamine was used when necessary.
MECT was used two times per week for 12 times.

2. Chlorpromazine Group: (n = 27)
management:
Newly hospitalised patients had to stop the previous drugs for three days and then were randomly divided into Zuclopenthixol Group or Chlorpromazine Group.
Chlorpromazine or Zuclopenthixol was enclosed in the same colour, style capsule by pharmacist.
In the first week of treatment, the dosage of Chlorpromazine was 200 mg/day and from the second week, it was increased 50 mg/day every week.

No other antipsychotic drugs were allowed during the treatment;

Trihexyphenidyl or scopolamine was used when necessary;

Outcomes

2. Global State ‐ Clinical response
4. Mental State ‐ BPRS score
8. Adverse effects ‐ Adverse events, TESS;

Unable to use: electrocardiogram; electroencephalogram; liver function; blood routine examination.

Notes

We have noticed that the N number does not always add up in this study, for example, the total sample size randomised was claimed to be 64, and 61 completed, but the number randomised to each group was reported as 33 and 27. Author to be contacted at next update.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Authors state patients randomised, not how

Allocation concealment (selection bias)

Unclear risk

Not reported after translation and data extraction

Blinding

Low risk

Double‐blind

Incomplete outcome data (attrition bias)
None

Unclear risk

N number unclear

Selective reporting (reporting bias)

Unclear risk

Not reported after translation and data extraction

Other bias

High risk

Berkson bias

BPRS ‐ Brief Psychiatric Rating Scale, CCMD‐3 ‐ Chinese classification of mental disorders,CGI ‐ Clinical Global Impression, CPRS (Montgomery 1979) ‐ Comprehensive Psychopathological Rating Scale, DSM ‐ Diagnostic and Statistical Manual of Mental Disorders, EPSEs ‐ extrapyramidal side‐effects, ESRS ‐ Extrapyramidal Symptom Rating Scale, ICD 10 ‐ International Classification of Diseases, RCT ‐ randomised controlled trial, MRI ‐ magnetic resonance imaging, NOSIE ‐ Nourses' Observation Scale for Inpatient Evaluation, PANSS ‐ Positive and Negative Syndrome Scale, PIP ‐ Psychotic Inpatient Profile, RCT ‐ randomised controlled trial, RDC ‐ Research Diagnostic Criteria, SANS ‐ Scale for the Assessment of Negative Symptoms, SD ‐ standard deviation, TESS ‐ Treatment Emergent Symptom Scale, UKU ‐ side effects scale.

Where possible, contact has been attempted with authors and/or institutions to seek clarification of bias and to obtain missing and/or unclear outcome data.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Aaes‐Jorgensen 1981a

Allocation: randomised.
Participants: healthy volunteers.

Ahlfors 1980

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: clopenthixol decanoate versus perphenazine enanthate, not oral form of zuclopenthixol.

Al Haddad 1996

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Arango 2002

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: oral ziclopenthixol versus depot zuclopenthixol.
outcomes: frequency of violent episodes (no data reported by group).

Baastrup 1993

Allocation: randomised.
Participants: people with acute psychosis, mania.

Bereen 1987

Allocation: not randomised, case‐series.

Bhattacharya 1987

Allocation: not randomised, case series.

Bobon 1989

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Bourdouxhe 1987

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Brook 1998

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Burke 2002

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: risperidone versus sulpiride, chlorpromazine, trifluoperazine, haloperidol, flupenthixol, zuclopenthixol.
Outcomes: SAPS and SANS scale, unable to use data.

Chin 1998

Allocation: randomised.
Participants: people with acute schizophrenia.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Chouinard 1991

Allocation: randomised.
Participants: people with acute schizophrenia.
Interventions: zuclopenthixol acetate versus liquid haloperidol, not oral form of zuclopenthixol.

Clark 1969

Allocation: not clear, double‐blind.
Participants: people with chronic schizophrenia.
Interventions: sordinol versus chlorpromazine versus placebo (unable to use data)

CTRI‐2014‐07‐004712

Wrong intervention.

Den 2000

Allocation: not clear, double‐blind.
Participants: people with schizophrenia.
Interventions: ritanserin versus placebo with other neuroleptics one of which was zuclopenthixol.
Outcomes: PANSS, CGI, ESRS, no usable date.

Dencker 1980

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: clopenthixol decanoate vesus flupenthixol palmitate, not oral form of zuclopenthixol.

Dom 1978

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: variable doses versus constant dose of zuclopenthixol decanoate, not oral form of zuclopenthixol.

Fagerlund 2003

Allocation: randomised, blindness not clear.
Participants: people with first‐episode schizophrenia.
Interventions: zuclopenthixol versus risperidone.
Outcomes: PANSS, cognitive function, no usable data.

Fan 1999

Not clear if oral or depot. Authors need to be contacted at next update.

Fensbo 1990

Allocation: randomised, double‐blind.
Participants: people with acute psychosis, exacerbation of chronic psychosis and mania.
Interventions: zuclopenthixol versus haloperidol.
Outcomes: leaving the study early, CGI, BPRS, no usable data.

Fricchione 2010

Depot not oral intervention.

Galdersi 1994

Originally included but excluded at this update. It is not an RCT and blindness is not mentioned.

Glenthoj 2000

Allocation: randomised.
Participants: people with first‐episode schizophrenia.
Interventions: risperidone versus zuclopenthixol.
Outcomes: PANSS, PPI, cognitive functions, no data provided.

Gravem 1990

Allocation: randomised.
Participants: people with schizophrenia, manic‐depressive illness, psychosis.
Interventions: zuclopenthixol acetate and zuclopenthixol decanoate, not oral form of zuclopenthixol.

Hicklin 1967

Allocation: not randomised.

Hovens 2003

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: risperidone + lorazepam versus zuclopenthixol + lorazepam; zuclopenthixol and lorazepam administered either in oral/injection form, not stated specifically for individual group.

Hovens 2005

Not randomised. Not blinded.

Huang 2001

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: zuclopenthixol decanoate versus clorpromazine, not oral form of zuclopenthixol.

Karsten 1981

Allocation: randomised.
Participants: people with oligophrenia.

Knegtering 2002a

Allocation: randomised.
Participants: people with psychosis.
Interventions: risperidone versus quetiapine, not oral form of zuclopenthixol.

Koskinen 1991

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: zuclopenthixol decanoate versus haloperidol decanoate, not oral form of zuclopenthixol.

Kristiansen 2001

Allocation: randomised.
Participants: healthy individuals.

Kristiansen 2003

No data.

Lamure 2003

Not oral form.

Lemmens 1994

Study duplicates data presented by authors already included in review.

Liu 1997b

injection not oral.

Liu 1998a

Injection not oral.

Loza 2001

Allocation: randomised.
Participants: people with first‐episode paranoid schizophrenia.
Interventions: typical antipsychotics (zuclopenthixol, perphenazine, haloperidol, perazine) versus atypical antipsychotics (risperidone, olanzapine, quetiapine).
Outcomes: PANSS, DL, WCST, no usable data.

Lublin 1991

Allocation: randomised.
Participants: Psychotic psychiatric in‐patients with tardive dyskinesia.
Interventions: concomitant use of zuclopenthixol and haloperidol.
Outcomes: CGI, BPRS, UKU side effects rating scale, no usable data.

Mackeprang 2001

Allocation: randomised.
Participants: people with first‐episode schizophrenia.
Interventions: zuclopenthixol versus risperidone.
Outcomes: SPECT, MRI, cognitive functions test, rapid visual information processing test.
E‐mailed author for outcomes. Deceased. Colleague replied that the data had not yet been published.
Unable to use data.

Malt 1995

Allocation: randomised.
Participants: people with learning disability.

Mann 1985

Allocation: not randomised, case series.

Martyns 1993

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: clopenthixol decanoate versus flupenthixol decanoate, not oral form of zuclopenthixol.

Mazurek 2003

Allocation: randomised.
Participants: people with paranoid schizophrenia.
Interventions: typical antipsychotics (zuclopenthixol, perphenazine, haloperidol, perazine, levomepromazine) vs atypical antipsychotics (risperidone, olanzapine, clozapine). Information about number of patients using each drug is not provided.

Meyers 1972

Allocation: not randomised.

Mosolov 2000

Allocation: randomised.
Participants: people with acute schizophrenia.
Interventions: after 2 day wash‐out period for group 1. clopixol acuphase i.m. for 7 days and then oral clopixol for 14 days. Group 2. halopeidol i.m. for 7 days and then oral form for 14 days (no usable data).

NCT00206960

No data.

Pagsberg 2004

Wrong intervention, no data.

Ropert 1988

Allocation: randomised.
Participants: people with psychosis, mania, chronic schizophrenia.
Interventions: zuclopenthixol acetate versus chlorpromazine, not oral form of zuclopenthixol.

Rubio 2005

Not oral form.

Rubio 2006

Zuclopenthixol depot.

Rubio 2009

Not oral form.

Rubioz 2006

Not oral form.

Saxena 1990b

Depot zuclopenthixol.

Saxena 1996

Allocation: not clear, double ‐blind.
Participants: people with schizophrenia.
interventions: zuclopenthixol decanoate versus fluphenazine decanoate, not oral form of zuclopenthixol.

Schooler 1993

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: antipsychotics (not mentioned) and family management.

Shelton 1969

Allocation: randomisation not clear.
Participants: people with schizophrenia.
Interventions: zuclopenthixol versus trifluoperazine.
Outcome: measurement of achilles reflex, no other data reported by group, unable to use data.

Singh 1992

Allocation: randomised.
Participants: mentally handicapped in‐patients with behavioural disorder with or without a psychiatric diagnosis.

Sofronov 2013

Depot zuclopenthixol.

Svestka 1986

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: clopenthixol decanoate versus oxyprothepine decanoate, not oral form of zuclopenthixol.

Syvalahti 1997

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: citalopram versus placebo with other neuroleptics i.e. haloperidol, chlorpromazine, levomepromazine, zuclopenthixol, thioridazine and perphenazine.
Outcomes: plasma concentrations of drugs, no usable data.

Taymeeyapradit 2002

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus haloperidol, not oral form of zuclopenthixol.

Tegeler 1985

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: clopenthixol decanoate versus fluphenazine decanoate, not oral form of zuclopenthixol.

Uys 1996

Allocation: randomised.
Participants: people with acute psychosis.
Interventions: zuclopenthixol acetate versus clothiapine, not oral form of zuclopenthixol.

Venkateswarlu 1990

Allocation: not randomised, case series.

Viala 1988

Allocation: randomised.
Participants: people with chronic psychosis.
Interventions: zuclopenthixol decanoate versus fluphenazine decanoate, not oral form of zuclopenthixol.

Walker 1983

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: clopenthixol decanoate versus fluphenazine decanoate, not oral form of zuclopenthixol.

Weiser 1975

Allocation: randomised.
Participants: people with acute schizophrenia.
Interventions: droperidol versus clopenthixol i. m. versus clozapine i.m., not oral form of zuclopenthixol.

Wisted 1990

Depot zuclopenthixol.

Wistedt 1991

Allocation: randomised.
Participants: people with chronic schizophrenia.
Interventions: zuclopenthixol decanoate versus haloperidol decanoate, not oral form of zuclopenthixol.

Xiaanao 1999

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: concomitant use of clopenthixol and other psychotropics.

Youssef 1991

Allocation: not clear.
Participants: people with psychosis.
Interventions: haloperidol decanoate versus other neuroleptics (fluphenazine decanoate, flupenthixol decanoate, clopenthixol decanoate, oral thioridazine, oral haloperidol, oral pimozide), not oral form of zuclopenthixol.

BPRS ‐ Brief Psychiatric Rating Scale, CGI ‐ Clinical Global Impression, ESRS ‐ Extrapyramidal Symptom Rating Scale, i.m. ‐ intramuscular, MRI ‐ magnetic resonance imaging, PANSS ‐ Positive and Negative Syndrome Scale, RCT ‐ randomised controlled trial, SANS ‐ Scale for the Assessment of Negative Symptoms, SAPS ‐ Scale for the Assessment of Positive Symptoms, UKU ‐ side effects scale.

Data and analyses

Open in table viewer
Comparison 1. ZUCLOPENTHIXOL versus PLACEBO ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

2

100

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

Analysis 1.1

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).

2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

Analysis 1.2

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.

3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 1.3

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.

3.1 excitation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.62 [0.12, 59.40]

3.2 sleepiness / sedation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.89 [1.01, 8.30]

4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started Show forest plot

1

36

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 126.48]

Analysis 1.4

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.

5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores) Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

6.07 [0.86, 43.04]

Analysis 1.5

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).

6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 1.6

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.

6.1 parkinsonism

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

6.2 oculogyric crisis

1

36

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.09]

6.3 tremor

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

Open in table viewer
Comparison 2. ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported) Show forest plot

2

135

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.75, 1.13]

Analysis 2.1

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).

2 Global state: 2. Average endpoint global state score ‐ No Recovery Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.89, 1.16]

Analysis 2.2

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.

3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐8.12, 6.92]

Analysis 2.3

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).

4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.49, 0.49]

Analysis 2.4

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).

5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported) Show forest plot

1

120

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.81, 1.18]

Analysis 2.5

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).

6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.25, 2.42]

Analysis 2.6

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.

7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2) Show forest plot

3

221

Mean Difference (IV, Random, 95% CI)

0.40 [‐2.43, 3.23]

Analysis 2.7

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).

8 Leaving the study early (any reason) Show forest plot

6

766

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.36, 0.81]

Analysis 2.8

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).

9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported) Show forest plot

1

94

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.77, 0.97]

Analysis 2.9

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).

10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

4.48 [‐2.38, 11.34]

Analysis 2.10

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).

11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope) Show forest plot

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.73]

Analysis 2.11

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).

12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 2.12

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.

12.1 excitation

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.07, 5.47]

12.2 sedation

2

163

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.73, 1.70]

13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds Show forest plot

1

29

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.22, 1.75]

Analysis 2.13

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.

14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

3

199

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.61, 1.45]

Analysis 2.14

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.

15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use Show forest plot

Other data

No numeric data

Analysis 2.15

Study

Zuclopenthixol

Chlorpromazine

Kingstone 1970

n = 5, authors do not state which additional medication.

n = 2, authors do not state which additional medication.

Kordas 1968

Benzhexol and diazepam if necessary.

Benzhexol and diazepam if necessary.

Wang 1995a

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.



Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use.

Open in table viewer
Comparison 3. ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 3.1

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.34, 2.93]

Analysis 3.2

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Open in table viewer
Comparison 4. ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

407

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Analysis 4.1

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day Show forest plot

Other data

No numeric data

Analysis 4.2

Study

Zuclopenthixol (n = 36)

Clozapine (n = 38)

Fischer‐Cornelssen 1976

Drowsiness (12%); Stimulation (14%); Confusion (1%); GI (1%); anticholinergic (14%); dizziness (6%); Orthostatic reaction (1%); Headache (2%); Hypersalivation (2%); hypokinesia (4%); hyperkinesia (2%); dyskinesia (0.4%); rigor (5%); tremor (5%); akathisia (3%)

Drowsiness (12%); Stimulation (21%); Confusion (3%); GI (8%); anticholinergic (8%); dizziness (15%); Orthostatic reaction (6%); Headache (3%); Hypersalivation (4%); hypokinesia (2%); hyperkinesia (4%); dyskinesia (0%); rigor (1%); tremor (3%); akathisia (3%)



Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day.

Open in table viewer
Comparison 5. ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 5.1

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25) Show forest plot

1

49

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.30, 0.55]

Analysis 5.2

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).

3 Leaving the study early (any reason) Show forest plot

2

141

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.72, 1.35]

Analysis 5.3

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 5.4

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.

5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 5.5

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.

6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 5.6

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.

7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 5.7

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.

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Comparison 6. ZUCLOPENTHIXOL versus PERPHENAZINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 6.1

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.

2 Leaving the study early (any reason) ‐ short/medium term Show forest plot

2

104

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.27, 1.47]

Analysis 6.2

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.

3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 6.3

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.

4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 6.4

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.

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Comparison 7. ZUCLOPENTHIXOL versus RISPERIDONE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐3.20 [‐7.71, 1.31]

Analysis 7.1

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.

2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

Analysis 7.2

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.

2.1 Short term

1

19

Mean Difference (IV, Random, 95% CI)

‐2.40 [‐4.52, ‐0.28]

2.2 Medium term

1

25

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐2.72, 2.12]

3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐2.69, 0.69]

Analysis 7.3

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.

4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.5 [‐4.05, 1.05]

Analysis 7.4

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.

5 Leaving the study early (any reason) ‐ short/medium term Show forest plot

3

154

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.84, 2.02]

Analysis 7.5

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.

6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term Show forest plot

Other data

No numeric data

Analysis 7.6

Study

Zuclopenthixol

Risperidone

Fagerlund 2004

Benzodiazepines n = 7

Anticholinergics n = 11

Benzodiazepines n = 8

Anticholinergics n = 7

Glenthoj 2007

Anticholinergic n = 10, Benzodiazepines n = 11, Antidepressant n = 1

Authors do not differentiate the use of additional medication between the two groups, totals only given.



Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term.

7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 7.7

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.

8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term Show forest plot

1

19

Mean Difference (IV, Random, 95% CI)

4.5 [0.67, 8.33]

Analysis 7.8

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.

9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 7.9

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.

9.1 UKU ‐ asthenia/lassitude/increased fatiguability

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.67, 1.01]

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Comparison 8. ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 8.1

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.75, 1.30]

Analysis 8.2

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).

3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7) Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.30 [‐5.08, 2.48]

Analysis 8.3

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).

4 Leaving the study early (any reason) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

2.07 [0.97, 4.40]

Analysis 8.4

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).

5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

Analysis 8.5

Study

Zuclopenthixol

Sulpiride

Mahadevan 1991

n = 4 Amitriptyline

n = 4 Amitryptyline



Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use.

6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.60 [‐8.35, 5.15]

Analysis 8.6

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.

7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 8.7

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.

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Comparison 9. ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Analysis 9.1

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.24, 1.35]

Analysis 9.2

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

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Comparison 10. ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

72

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Analysis 10.1

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

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Comparison 11. ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.95 [0.36, 10.58]

Analysis 11.1

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).

2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.44, 1.71]

Analysis 11.2

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.

3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

Analysis 11.3

Study

Zuclopenthixol

Depot

Arango 2006

n = 1 Propanolol

n = 1 venlafaxine

n = 1 Lithium



Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use.

4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.3 [0.59, 2.86]

Analysis 11.4

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.

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Comparison 12. CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unwell Show forest plot

3

131

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.80, 1.17]

Analysis 12.1

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.

2 Mental state: Average endpoint general mental state score ‐ Not improved Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.45, 2.07]

Analysis 12.2

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.

3 Leaving the study early (any reason) Show forest plot

4

140

Risk Ratio (M‐H, Random, 95% CI)

2.15 [0.49, 9.41]

Analysis 12.3

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.82, 2.18]

Analysis 12.4

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.

5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects Show forest plot

Other data

No numeric data

Analysis 12.5

Study

Cis Z

Cis(Z)/Trans(E)

Gravem 1981

EPSEs most frequent.

Authors state no significant difference between two isomers.

EPSEs most frequent.

Heikkila 1981

Dry mouth, Disturbance of accommodation, Disturbance of urination, Constipation, Dizziness, Headache, Increased sweating, Drowsiness, Anxiety, Parkinsonism, Akathisia, Tardive dyskinesia and others

Dry mouth, Disturbance of urination, Constipation, Dizziness, Drowsiness, Parkinsonism, Akathisia, Tardive dyskinesia, others



Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects.

Study flow diagram ‐ update 2016.
Figuras y tablas -
Figure 1

Study flow diagram ‐ update 2016.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figuras y tablas -
Analysis 1.1

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.
Figuras y tablas -
Analysis 1.2

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.
Figuras y tablas -
Analysis 1.3

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.
Figuras y tablas -
Analysis 1.4

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started.

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).
Figuras y tablas -
Analysis 1.5

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores).

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.
Figuras y tablas -
Analysis 1.6

Comparison 1 ZUCLOPENTHIXOL versus PLACEBO ‐ all short term, Outcome 6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).
Figuras y tablas -
Analysis 2.1

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.
Figuras y tablas -
Analysis 2.2

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score ‐ No Recovery.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).
Figuras y tablas -
Analysis 2.3

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).
Figuras y tablas -
Analysis 2.4

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).
Figuras y tablas -
Analysis 2.5

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.
Figuras y tablas -
Analysis 2.6

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).
Figuras y tablas -
Analysis 2.7

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).
Figuras y tablas -
Analysis 2.8

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 8 Leaving the study early (any reason).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).
Figuras y tablas -
Analysis 2.9

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).
Figuras y tablas -
Analysis 2.10

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).
Figuras y tablas -
Analysis 2.11

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope).

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.
Figuras y tablas -
Analysis 2.12

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.
Figuras y tablas -
Analysis 2.13

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds.

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.
Figuras y tablas -
Analysis 2.14

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs.

Study

Zuclopenthixol

Chlorpromazine

Kingstone 1970

n = 5, authors do not state which additional medication.

n = 2, authors do not state which additional medication.

Kordas 1968

Benzhexol and diazepam if necessary.

Benzhexol and diazepam if necessary.

Wang 1995a

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.

Trihexphenidyl or scopolamine used if necessary. Authors do not report frequency of use or which group used which.

Figuras y tablas -
Analysis 2.15

Comparison 2 ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term, Outcome 15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use.

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).
Figuras y tablas -
Analysis 3.1

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).
Figuras y tablas -
Analysis 3.2

Comparison 3 ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figuras y tablas -
Analysis 4.1

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Study

Zuclopenthixol (n = 36)

Clozapine (n = 38)

Fischer‐Cornelssen 1976

Drowsiness (12%); Stimulation (14%); Confusion (1%); GI (1%); anticholinergic (14%); dizziness (6%); Orthostatic reaction (1%); Headache (2%); Hypersalivation (2%); hypokinesia (4%); hyperkinesia (2%); dyskinesia (0.4%); rigor (5%); tremor (5%); akathisia (3%)

Drowsiness (12%); Stimulation (21%); Confusion (3%); GI (8%); anticholinergic (8%); dizziness (15%); Orthostatic reaction (6%); Headache (3%); Hypersalivation (4%); hypokinesia (2%); hyperkinesia (4%); dyskinesia (0%); rigor (1%); tremor (3%); akathisia (3%)

Figuras y tablas -
Analysis 4.2

Comparison 4 ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term, Outcome 2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).
Figuras y tablas -
Analysis 5.1

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).
Figuras y tablas -
Analysis 5.2

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).
Figuras y tablas -
Analysis 5.3

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.
Figuras y tablas -
Analysis 5.4

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.
Figuras y tablas -
Analysis 5.5

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.
Figuras y tablas -
Analysis 5.6

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication.

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.
Figuras y tablas -
Analysis 5.7

Comparison 5 ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term, Outcome 7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.
Figuras y tablas -
Analysis 6.1

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.
Figuras y tablas -
Analysis 6.2

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 2 Leaving the study early (any reason) ‐ short/medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.
Figuras y tablas -
Analysis 6.3

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term.

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.
Figuras y tablas -
Analysis 6.4

Comparison 6 ZUCLOPENTHIXOL versus PERPHENAZINE, Outcome 4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.
Figuras y tablas -
Analysis 7.1

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.
Figuras y tablas -
Analysis 7.2

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.
Figuras y tablas -
Analysis 7.3

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.
Figuras y tablas -
Analysis 7.4

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.
Figuras y tablas -
Analysis 7.5

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 5 Leaving the study early (any reason) ‐ short/medium term.

Study

Zuclopenthixol

Risperidone

Fagerlund 2004

Benzodiazepines n = 7

Anticholinergics n = 11

Benzodiazepines n = 8

Anticholinergics n = 7

Glenthoj 2007

Anticholinergic n = 10, Benzodiazepines n = 11, Antidepressant n = 1

Authors do not differentiate the use of additional medication between the two groups, totals only given.

Figuras y tablas -
Analysis 7.6

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.
Figuras y tablas -
Analysis 7.7

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.
Figuras y tablas -
Analysis 7.8

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term.

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.
Figuras y tablas -
Analysis 7.9

Comparison 7 ZUCLOPENTHIXOL versus RISPERIDONE, Outcome 9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).
Figuras y tablas -
Analysis 8.1

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).
Figuras y tablas -
Analysis 8.2

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).
Figuras y tablas -
Analysis 8.3

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7).

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).
Figuras y tablas -
Analysis 8.4

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 4 Leaving the study early (any reason).

Study

Zuclopenthixol

Sulpiride

Mahadevan 1991

n = 4 Amitriptyline

n = 4 Amitryptyline

Figuras y tablas -
Analysis 8.5

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.
Figuras y tablas -
Analysis 8.6

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change.

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.
Figuras y tablas -
Analysis 8.7

Comparison 8 ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term, Outcome 7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives.

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).
Figuras y tablas -
Analysis 9.1

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI).

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).
Figuras y tablas -
Analysis 9.2

Comparison 9 ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term, Outcome 2 Leaving the study early (any reason).

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).
Figuras y tablas -
Analysis 10.1

Comparison 10 ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term, Outcome 1 Leaving the study early (any reason).

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).
Figuras y tablas -
Analysis 11.1

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 1 Leaving the study early (any reason).

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.
Figuras y tablas -
Analysis 11.2

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up.

Study

Zuclopenthixol

Depot

Arango 2006

n = 1 Propanolol

n = 1 venlafaxine

n = 1 Lithium

Figuras y tablas -
Analysis 11.3

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use.

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.
Figuras y tablas -
Analysis 11.4

Comparison 11 ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term, Outcome 4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.
Figuras y tablas -
Analysis 12.1

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 1 Global state: Average endpoint global state score ‐ Unwell.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.
Figuras y tablas -
Analysis 12.2

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 2 Mental state: Average endpoint general mental state score ‐ Not improved.

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).
Figuras y tablas -
Analysis 12.3

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 3 Leaving the study early (any reason).

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.
Figuras y tablas -
Analysis 12.4

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported.

Study

Cis Z

Cis(Z)/Trans(E)

Gravem 1981

EPSEs most frequent.

Authors state no significant difference between two isomers.

EPSEs most frequent.

Heikkila 1981

Dry mouth, Disturbance of accommodation, Disturbance of urination, Constipation, Dizziness, Headache, Increased sweating, Drowsiness, Anxiety, Parkinsonism, Akathisia, Tardive dyskinesia and others

Dry mouth, Disturbance of urination, Constipation, Dizziness, Drowsiness, Parkinsonism, Akathisia, Tardive dyskinesia, others

Figuras y tablas -
Analysis 12.5

Comparison 12 CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term, Outcome 5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects.

Summary of findings for the main comparison. Zuclopenthixol dihydrochloride versus placebo

Patient or population: people with schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: PLACEBO (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with PLACEBO (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (extrapyramidal effects ‐ UKU side effect rating scale)

80 per 1000

486 per 1000
(69 to 1000)

RR 6.07
(0.86 to 43.04)

28
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2, 3,4, 5, 6

Risk assumed to be moderate and rounded from 7.69% to 8%.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: Duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

40 per 1000

12 per 1000
(0 to 264)

RR 0.29
(0.01 to 6.60)

100
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1, 6

Risk assumed to be moderate and rounded from 3.85% to 4%. Low number of events in both RCTs.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated 'very serious' ‐ possible selection bias, blinding may have been single, attrition bias and reporting bias.

2 Risk of bias: rated 'very serious' ‐ selection, attrition and reporting bias

3 Risk of inconsistency: rated 'not serious' ‐ suspected but not found.

4 Risk of publication bias: rated 'strongly suspected' ‐ multiple papers published with the same patient cohort.

5 Risk of large effect: rated 'very large' ‐ RR 6.07, small n number but result likely when versus placebo.

6 Risk of imprecision: rated 'very serious' ‐ low n numbers

Figuras y tablas -
Summary of findings for the main comparison. Zuclopenthixol dihydrochloride versus placebo
Summary of findings 2. Zuclopenthixol dihydrochloride versus chlorpromazine

Patient or population: schizophrenia
Setting: Outpatient and inpatient (predominantly hospitalised)
Intervention: ZUCLOPENTHIXOL
Comparison: CHLORPROMAZINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CHLORPROMAZINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI‐SI, high score not reported, average score = 2.2)

The mean CGI‐SI endpoint score in the intervention group (MD) was 0 (‐0.49 lower to 0.49 higher)

64
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 5

Translated study.

Adverse effects: Clinically important general adverse effect (EPSEs)

300 per 1000

282 per 1000
(183 to 435)

RR 0.94
(0.61 to 1.45)

199
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 2 4 5 6

Risk control rounded to 30% and set to moderate. Mixture of inpatient and outpatient, though predominantly hospitalised patients.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (BPRS, high score = 34.2)

The mean mental state: average endpoint score (BPRS, high score = 34.2) in the intervention group was 0.4 more (2.43 fewer to 3.23 more)

221
(3 RCTs)

⊕⊕⊝⊝
LOW 2 6

Mixture of inpatient and outpatient, though predominantly hospitalised patients.

Leaving the study early (any reason)

70 per 1000

38 per 1000
(25 to 57)

RR 0.54
(0.36 to 0.81)

766
(6 RCTs)

⊕⊕⊝⊝
LOW 3 6

Mixture of inpatient and outpatient, though predominantly hospitalised patients. Risk control set to moderate and rounded to 7%; extreme values not likely.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated 'serious' ‐ Selection and attrition bias likely.

2 Risk of bias: rated 'serious' ‐ Selection attrition bias.

3 Risk of bias: rated 'serious' ‐ Selection, attrition and reporting bias.

4 Risk of bias: rated 'serious' ‐ Selection, attrition and reporting bias. Risk of inconsistency: rated as 'serious' ‐ All three papers reported on differing population sizes and obtained different levels of EPSEs in the experimental and control groups.

5 Risk of imprecision: rated 'very serious' ‐ low n numbers

6 Risk of indirectness: rated 'very serious' ‐ mixed samples

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 2. Zuclopenthixol dihydrochloride versus chlorpromazine
Summary of findings 3. Zuclopenthixol dihydrochloride versus chlorprothixene

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: CHLORPROTHIXENE (medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CHLORPROTHIXENE (medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

400 per 1000

400 per 1000
(136 to 1000)

RR 1.00
(0.34 to 2.93)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, reporting bias likely.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same cohort of patients.

3 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 3. Zuclopenthixol dihydrochloride versus chlorprothixene
Summary of findings 4. Zuclopenthixol dihydrochloride versus clozapine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: CLOZAPINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CLOZAPINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Leaving the study early (any reason)

0 per 1000

0 per 1000
(0 to 0)

not estimable

407
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

Multi‐centre, multi‐drug trial with disproportionate numbers of people in different arms of the study. The authors did not report that anybody left the study in the Zuclopenthixol and clozapine arms.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, attrition, reporting and performance bias likely.

2 Risk of indirectness: rated 'serious' ‐ Multiple study arms

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 4. Zuclopenthixol dihydrochloride versus clozapine
Summary of findings 5. Zuclopenthixol dihydrochloride versus haloperidol

Patient or population: schizophrenia
Setting: Hospital only.
Intervention: ZUCLOPENTHIXOL
Comparison: HALOPERIDOL (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with HALOPERIDOL (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI, mean score = 1.25)

The mean CGI endpoint score in the intervention group (MD) was 0.13 more (‐0.3 fewer to 0.55 more)

49
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 3 4

Small study, multiple scales used (NOSIE30, BPRS, CGI). Paper only reported outcomes of some of these scales.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

300 per 1000

297 per 1000
(216 to 405)

RR 0.99
(0.72 to 1.35)

141
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 3 4

Risk control rounded to 30% from 29.25% and, as extreme values unlikely, it was set to moderate.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ likely selection, attrition, reporting and diagnostic purity bias.

2 Risk of bias: rated as 'serious' ‐ likely selection, attrition, reporting and diagnostic purity bias. Risk of inconsistency: rated as 'serious' ‐ both papers generated differing values for people leaving the study and do not appear consistent (face validity).

3 Risk of imprecision: rated 'serious' ‐ low n numbers

4 Risk of indirectness: rated 'serious' ‐ not all scales reported

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 5. Zuclopenthixol dihydrochloride versus haloperidol
Summary of findings 6. Zuclopenthixol dihydrochloride versus perphenazine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: PERPHENAZINE (short and medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with PERPHENAZINE (short and medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (EPSEs requiring medication ‐ medium term)

400 per 1000

760 per 1000
(448 to 1000)

RR 1.90
(1.12 to 3.22)

50
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason, short and medium term)

207 per 1000

130 per 1000
(56 to 304)

RR 0.63
(0.27 to 1.47)

104
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ likely selection and reporting bias.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 6. Zuclopenthixol dihydrochloride versus perphenazine
Summary of findings 7. Zuclopenthixol dihydrochloride versus risperidone

Patient or population: schizophrenia
Setting: Mostly hospital. Huttunen group did not state
Intervention: ZUCLOPENTHIXOL
Comparison: RISPERIDONE (short and medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with RISPERIDONE (short and medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Adverse effects: Clinically important general adverse effect ‐ short term (EPSEs requiring medication)

271 per 1000

520 per 1000
(303 to 888)

RR 1.92
(1.12 to 3.28)

98
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2 5 6

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (PANSS, average score = 20.5) ‐ medium term

The mean PANNS endpoint score in the intervention group (MD) was 3.2 fewer (‐7.71 fewer to 1.31 more)

25
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Small study. Standard deviations may be standard errors. Open label trial.

Leaving the study early (any reason, short and medium term)

310 per 1000

403 per 1000
(260 to 626)

RR 1.30
(0.84 to 2.02)

154
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 3 4

Risk control taken as mean of extremes: high + low / 2 (changed from 21.43% to 31%)

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ open label trial, likely selection bias.

2 Risk of imprecision: rated as 'very serious' ‐ strongly suspect reported standard deviations are standard errors, low n numbers

3 Risk of publication bias: rated as 'strongly suspected' ‐ all studies published findings across several consecutive years in different journals and at conferences.

4 Risk of bias: rated as 'very serious' ‐ study 1 (selection, reporting, diagnostic purity and attrition bias likely ‐ author emailed); study 2 (open label); study 3 (reporting and attrition bias).

5 Risk of publication bias: rated as 'strongly suspected' ‐ multiple papers over consecutive years published with the same data.

6 Risk of bias: rated as 'serious' ‐ diagnostic purity and attrition bias; likely selection and reporting bias (authors contacted)

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 7. Zuclopenthixol dihydrochloride versus risperidone
Summary of findings 8. Zuclopenthixol dihydrochloride versus sulpiride

Patient or population: schizophrenia
Setting: Not specified in study.
Intervention: ZUCLOPENTHIXOL
Comparison: SULPIRIDE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with SULPIRIDE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (CGI ‐ unchanged/worse)

226 per 1000

266 per 1000
(111 to 644)

RR 1.18
(0.49 to 2.85)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

The study did not report clinical improvement so unchanged/worse is reported for this outcome. Usually we report clinical improvement.

Adverse effects: Clinically important general adverse effect ‐ requiring hypnotics/sedatives

419 per 1000

252 per 1000
(113 to 554)

RR 0.60
(0.27 to 1.32)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (BPRS)

The mean BPRS endpoint score in the intervention group (MD) was 1.3 fewer (‐5.08 fewer to 2.48 more)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Leaving the study early (any reason)

230 per 1000

476 per 1000
(223 to 1000)

RR 2.07
(0.97 to 4.40)

61
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Control of risk rounded up from 22.58% to 23%.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ diagnostic purity, attrition bias. Per‐Protocol analysis suspected.

2 Risk of imprecision: rated as ' very serious' ‐ percentages used to describe data and comparisons are made against an assumption of baseline measurements. Low n numbers.

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 8. Zuclopenthixol dihydrochloride versus sulpiride
Summary of findings 9. Zuclopenthixol dihydrochloride versus thiothixene

Patient or population: schizophrenia
Setting: hospital
Intervention: ZUCLOPENTHIXOL
Comparison: THIOTHIXENE (medium term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with THIOTHIXENE (medium term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (unchanged/worse ‐ CGI)

600 per 1000

300 per 1000
(102 to 876)

RR 0.50
(0.17 to 1.46)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

The study did not report clinical improvement so unchanged/worse is reported for this outcome. Usually we report clinical improvement.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

Leaving the study early (any reason)

700 per 1000

399 per 1000
(168 to 945)

RR 0.57
(0.24 to 1.35)

20
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No studies reported on this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ likely selection and reporting bias.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same cohort.

3 Risk of imprecision: rated as 'serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 9. Zuclopenthixol dihydrochloride versus thiothixene
Summary of findings 10. Zuclopenthixol dihydrochloride versus trifluoperazine

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: TRIFLUOPERAZINE (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with TRIFLUOPERAZINE (short term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

0 per 1000

0 per 1000
(0 to 0)

not estimable

72
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Multi‐centre and multi‐drug trial with low numbers in each arm.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection, attrition, reporting and performance bias likely.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

3 Risk of indirectness: rated 'very serious' ‐ multiple arms, some missing

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 10. Zuclopenthixol dihydrochloride versus trifluoperazine
Summary of findings 11. Zuclopenthixol dihydrochloride versus zuclopenthixol depot

Patient or population: schizophrenia
Setting: Hospital
Intervention: ZUCLOPENTHIXOL
Comparison: ZUCLOPENTHIXOL DEPOT (long term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with ZUCLOPENTHIXOL DEPOT (long term)

Risk with ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early (any reason)

80 per 1000

156 per 1000
(29 to 846)

RR 1.95
(0.36 to 10.58)

46
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2 3

Control of risk rounded from 7.69% to 8%.

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'very serious' ‐ single researcher did randomisation, selection bias likely, open label trial and incomplete outcome data.

2 Risk of publication bias: rated as 'strongly suspected' ‐ several papers published using the same data and cohort.

3 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 11. Zuclopenthixol dihydrochloride versus zuclopenthixol depot
Summary of findings 12. Zuclopenthixol dihydrochloride (Cis Z isomer) versus Zuclopenthixol (Cis Z/Trans E isomer)

Patient or population: schizophrenia
Setting: Mostly inpatient. 4 Studies included of which two did not state but implied inpatient.
Intervention: CIS‐(Z) ZUCLOPENTHIXOL
Comparison: CIS(Z)/TRANS(E) ZUCLOPENTHIXOL (short term)

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with CIS(Z)/TRANS(E) ZUCLOPENTHIXOL (short term)

Risk with CIS‐(Z) ZUCLOPENTHIXOL

Global state: Average endpoint global state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Adverse effects: Clinically important general adverse effect

470 per 1000

630 per 1000
(385 to 1000)

RR 1.34
(0.82 to 2.18)

57
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1 2

Control of risk set at moderate and rounded up from 46.4% to 47%.

Death: Suicide and natural causes (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Service outcomes: duration of stay in hospital (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Mental state: Average endpoint general mental state score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

Leaving the study early: Any reason

28 per 1000

61 per 1000
(14 to 265)

RR 2.15
(0.49 to 9.41)

140
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2

General functioning: Average endpoint general functioning score (clinically improved) (no data)

not pooled

not pooled

not estimable

(0 studies)

No study reported this outcome.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Risk of bias: rated as 'serious' ‐ selection bias throughout. Very difficult to ascertain from published materials if selection bias has been minimised.

2 Risk of imprecision: rated 'very serious' ‐ low n numbers

For risks rated as serious, we downgraded by 1.

For risks rated as very serious we downgraded by 2.

Figuras y tablas -
Summary of findings 12. Zuclopenthixol dihydrochloride (Cis Z isomer) versus Zuclopenthixol (Cis Z/Trans E isomer)
Comparison 1. ZUCLOPENTHIXOL versus PLACEBO ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

2

100

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

2 Adverse effects: 1. Clinically important change in specific adverse effects ‐ cardiovascular ‐ orthostatic Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.01, 6.60]

3 Adverse effects: 2. Clinically important change in specific adverse effects ‐ central nervous system ‐ arousal state Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 excitation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.62 [0.12, 59.40]

3.2 sleepiness / sedation

1

28

Risk Ratio (M‐H, Random, 95% CI)

2.89 [1.01, 8.30]

4 Adverse effects: 3. Clinically important change in specific adverse effects ‐ endocrine ‐ menstruation started Show forest plot

1

36

Risk Ratio (M‐H, Random, 95% CI)

7.0 [0.39, 126.48]

5 Adverse effects: 4a. Any general adverse effects ‐ movement disorders ‐ EPSEs (UKU side effect rating scale, no scores) Show forest plot

1

28

Risk Ratio (M‐H, Random, 95% CI)

6.07 [0.86, 43.04]

6 Adverse effects: 4b. Clinically important change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 parkinsonism

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

6.2 oculogyric crisis

1

36

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.09]

6.3 tremor

1

36

Risk Ratio (M‐H, Random, 95% CI)

5.00 [0.26, 97.37]

Figuras y tablas -
Comparison 1. ZUCLOPENTHIXOL versus PLACEBO ‐ all short term
Comparison 2. ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI, scores not reported) Show forest plot

2

135

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.75, 1.13]

2 Global state: 2. Average endpoint global state score ‐ No Recovery Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.89, 1.16]

3 Global state: 3a. Average endpoint global state score (GAS, high score not reported, average score = 63.4) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

‐0.60 [‐8.12, 6.92]

4 Global state: 3b. Average endpoint global state score (CGI‐SI, high score not reported, average score = 2.2) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.49, 0.49]

5 Mental state: 1. No clinically important change in general mental state ‐ Not improved (PANSS, scores not reported) Show forest plot

1

120

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.81, 1.18]

6 Mental state: 2. No clinically important change in general mental state ‐ No clinical response Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.25, 2.42]

7 Mental state: 3. Average endpoint general mental state score (BPRS, high score = 34.2) Show forest plot

3

221

Mean Difference (IV, Random, 95% CI)

0.40 [‐2.43, 3.23]

8 Leaving the study early (any reason) Show forest plot

6

766

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.36, 0.81]

9 Adverse effects: 1. Any general adverse effects ‐ side effects (CGI, high score not reported) Show forest plot

1

94

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.77, 0.97]

10 Adverse effects: 2. Average endpoint general adverse effect score ‐ average score (TESS, high score not reported, average score = 12.00) Show forest plot

1

60

Mean Difference (IV, Random, 95% CI)

4.48 [‐2.38, 11.34]

11 Adverse effects: 3. Any change in specific adverse effects ‐ cardiovascular ‐ postural hypotension (dizziness/syncope) Show forest plot

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 1.73]

12 Adverse effects: 4. Any change in specific adverse effects ‐ central nervous system ‐ arousal Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

12.1 excitation

1

43

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.07, 5.47]

12.2 sedation

2

163

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.73, 1.70]

13 Adverse effects: 5. Any change in specific adverse effects ‐ metabolic ‐ weight change ‐ loss or gain of weight of 10 pounds Show forest plot

1

29

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.22, 1.75]

14 Adverse effects: 6a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs Show forest plot

3

199

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.61, 1.45]

15 Adverse effects: 6b. Any change in specific adverse effects ‐ movement disorders ‐ additional medication use Show forest plot

Other data

No numeric data

Figuras y tablas -
Comparison 2. ZUCLOPENTHIXOL versus CHLORPROMAZINE ‐ all short term
Comparison 3. ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.34, 2.93]

Figuras y tablas -
Comparison 3. ZUCLOPENTHIXOL versus CHLORPROTHIXENE ‐ all medium term
Comparison 4. ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

407

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Adverse effects: Any general adverse effects ‐ side effects ‐ frequency per day Show forest plot

Other data

No numeric data

Figuras y tablas -
Comparison 4. ZUCLOPENTHIXOL versus CLOZAPINE ‐ all short term
Comparison 5. ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Global state: 2. Average endpoint global state score (CGI, mean score = 1.25) Show forest plot

1

49

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.30, 0.55]

3 Leaving the study early (any reason) Show forest plot

2

141

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.72, 1.35]

4 Adverse effects: 1. Any change in specific adverse effects ‐ interference with functioning Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7 Adverse effects: 4. Any change in specific adverse effects ‐ requiring hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 5. ZUCLOPENTHIXOL versus HALOPERIDOL ‐ all short term
Comparison 6. ZUCLOPENTHIXOL versus PERPHENAZINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (global rating ‐ investigator opinion) ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) ‐ short/medium term Show forest plot

2

104

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.27, 1.47]

3 Adverse effects: 1. Any change in specific adverse effects ‐ central nervous system ‐ arousal ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4 Adverse effects: 2. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ medium term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 6. ZUCLOPENTHIXOL versus PERPHENAZINE
Comparison 7. ZUCLOPENTHIXOL versus RISPERIDONE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental State: 1. Average endpoint general mental state score (PANSS, average score = 45.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐3.20 [‐7.71, 1.31]

2 Mental State: 2. Average endpoint general mental state score (PANSS General, average score medium term = 20.5) ‐ short/medium term Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Short term

1

19

Mean Difference (IV, Random, 95% CI)

‐2.40 [‐4.52, ‐0.28]

2.2 Medium term

1

25

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐2.72, 2.12]

3 Mental State: 3. Average endpoint general mental state score (PANSS Positive, average score = 9.8) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐2.69, 0.69]

4 Mental State: 4. Average endpoint general mental state score (PANSS Negative, average score 11.5) ‐ medium term Show forest plot

1

25

Mean Difference (IV, Random, 95% CI)

‐1.5 [‐4.05, 1.05]

5 Leaving the study early (any reason) ‐ short/medium term Show forest plot

3

154

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.84, 2.02]

6 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use ‐ short/medium term Show forest plot

Other data

No numeric data

7 Adverse effects: 2a. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs ‐ requiring medication ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8 Adverse Effects: 2b. Any change in specific adverse effects ‐ movement disorders ‐ EPSEs (ESRS) ‐ short term Show forest plot

1

19

Mean Difference (IV, Random, 95% CI)

4.5 [0.67, 8.33]

9 Adverse effects: 3. Any change in specific adverse effects ‐ negative and cognitive symptoms of schizophrenia ‐ short term Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 UKU ‐ asthenia/lassitude/increased fatiguability

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.67, 1.01]

Figuras y tablas -
Comparison 7. ZUCLOPENTHIXOL versus RISPERIDONE
Comparison 8. ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: 1. Average endpoint global state score ‐ Unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Global State: 2. Average endpoint global state score ‐ Moderately or severely ill (CGI) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.75, 1.30]

3 Mental State: Average endpoint general mental state score (BPRS, average = 5.7) Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.30 [‐5.08, 2.48]

4 Leaving the study early (any reason) Show forest plot

1

61

Risk Ratio (M‐H, Random, 95% CI)

2.07 [0.97, 4.40]

5 Adverse Effects: 1. Any change in general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

6 Adverse Effects: 2. Any change in specific adverse effects ‐ metabolic ‐ weight change Show forest plot

1

61

Mean Difference (IV, Random, 95% CI)

‐1.60 [‐8.35, 5.15]

7 Adverse effects: 3. Any change in specific adverse effects ‐ requiring additional medication ‐ hypnotics/sedatives Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 8. ZUCLOPENTHIXOL versus SULPIRIDE ‐ all short term
Comparison 9. ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ unchanged/worse (CGI) Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2 Leaving the study early (any reason) Show forest plot

1

20

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.24, 1.35]

Figuras y tablas -
Comparison 9. ZUCLOPENTHIXOL versus THIOTHIXENE ‐ all medium term
Comparison 10. ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

72

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 10. ZUCLOPENTHIXOL versus TRIFLUOPERAZINE ‐ all short term
Comparison 11. ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Leaving the study early (any reason) Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.95 [0.36, 10.58]

2 Behaviour: Average change in specific aspects of behaviour ‐ Violence during follow‐up Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.44, 1.71]

3 Adverse Effects: 1a. Any general adverse effects ‐ additional medication use Show forest plot

Other data

No numeric data

4 Adverse Effects: 1b. Any change in specific adverse effects ‐ additional medication use ‐ benzodiazepine use at least once Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

1.3 [0.59, 2.86]

Figuras y tablas -
Comparison 11. ZUCLOPENTHIXOL versus ZUCLOPENTHIXOL DEPOT ‐ all long term
Comparison 12. CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global state: Average endpoint global state score ‐ Unwell Show forest plot

3

131

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.80, 1.17]

2 Mental state: Average endpoint general mental state score ‐ Not improved Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.45, 2.07]

3 Leaving the study early (any reason) Show forest plot

4

140

Risk Ratio (M‐H, Random, 95% CI)

2.15 [0.49, 9.41]

4 Adverse Effects: 1a. Any general adverse effects ‐ side effects reported Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.82, 2.18]

5 Adverse Effects: 1b. Any change in specific adverse effects ‐ individual side effects Show forest plot

Other data

No numeric data

Figuras y tablas -
Comparison 12. CIS‐(Z) ZUCLOPENTHIXOL versus CIS(Z)/TRANS(E) ZUCLOPENTHIXOL ‐ all short term