Chlorpromazine dose for people with schizophrenia

Katharine Dudley; Xiaomeng Liu; Saskia De Haan

doi:10.1002/14651858.CD007778.pub2

نقش دوز کلورپرومازین برای درمان افراد مبتلا به اسکیزوفرنی

Contraer todo Desplegar todo

Referencias

منابع مطالعات واردشده در این مرور

Ir a:

منابع مطالعات خارج‌شده از این مرور
منابع اضافی
منابع دیگر نسخه‌های منتشرشده این مرور

Chouinard G, Annable L. Alpha‐methyldopa‐chlorpromazine combination in schizophrenic patients. Neuropsychobiology 1976;2(2‐3):118‐26.

Clark M, Dubowski K, Colmore J. The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients. Clinical Pharmacology and Therapeutics 1970;11:883‐9.

Clark ML, Ramsey HR, Ragland RE, Rahhal DK, Serafetinides EA, Costiloe JP. Chlorpromazine in chronic schizophrenia ‐ behavioral dose‐response relationships. Psychopharmacology [Psychopharmacologia] 1970;18(3):260‐70.

Clark ML, Ramsey HR, Rahhal DK, Serafetinides EA, Wood FD, Costiloe JP. Chlorpromazine in chronic schizophrenia. The effect of age and hospitalization on behavioral dose‐response relationships. Archives of General Psychiatry 1972;27(4):479‐83.

Serafetinides EA, Willis D, Clark ML. EEG dose‐response relationships of chlorpromazine in chronic schizophrenia: the effects on the various rhythms and on alpha blocking. Biological Psychiatry 1972;4:251‐6.

Ayd FJ. Neuroleptic therapy for chronic schizophrenia. Diseases of the Nervous System 1972;33(1):35‐9. [MEDLINE: 5059687]

De Long SL. Incidence and significance of chlorpromazine‐induced eye changes. Diseases of the Nervous System 1968;29:19‐22.

Google Scholar

Gardos G, Cole JO, LaBrie RA. A 12 year follow up study of chronic schizophrenics. Hospital and Community Psychiatry 1982;33(12):983‐4.

Prien RF, Cole JO. High dose chlorpromazine therapy in chronic schizophrenia. Report of National Institute of Mental Health ‐ psychopharmacology research branch collaborative study group. Archives of General Psychiatry 1968;18(4):482‐95.

Prien RF, Cole JO, Belkin NF. Relapse in chronic schizophrenics following abrupt withdrawal of tranquillizing medication. British Journal of Psychiatry 1968;115(523):679‐86.

Prien RF, DeLong SL, Cole JO, Levine J. Ocular changes occurring with prolonged high dose chlorpromazine therapy. Results from a collaborative study. Archives of General Psychiatry 1970;23(5):464‐8.

Prien RF, Levine J, Cole JO. High dose therapy in chronic schizophrenia ‐ trifuoperazine. 121st Annual Meeting of the American Psychiatric Association; 1968 May 13‐17; Boston (MA). Boston (MA): American Psychiatric Association, 1968.

Google Scholar

Prien RF, Levine J, Cole JO. Indications for high dose chlorpromazine therapy in chronic schizophrenia. Diseases of the Nervous System 1970;31(11):739‐45.

Prien RF, Levine J, Switalski RW. Discontinuation of chemotherapy for chronic schizophrenics. Hospital and Community Psychiatry 1971;22(1):4‐7. [MEDLINE: 4992967]

Wode‐Helgodt B, Borg S, Fyro B, Sedvall G. Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiatrica Scandinavica 1978;58(2):149‐73.

Wode‐Helgodt B, Eneroth P, Fyro B, Gullberg B, Sedvall G. Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients. Acta Psychiatrica Scandinavica 1977;56(4):280‐93.

Wode‐Helgodt B, Fyro B, Gullberg B, Sedvall G. Effect of chlorpromazine treatment on monoamine metabolite levels in cerebrospinal fluid of psychotic patients. Acta Psychiatrica Scandinavica 1977;56(2):129‐42.

Xu Y, Gao H, Li M, Li X. Different doses of clozapine and chlorpromazine in the treatment of schizophrenia clinical research. Archives of Psychiatry 2009;22(3):203‐4.

Google Scholar

منابع مطالعات خارج‌شده از این مرور

Ir a:

منابع مطالعات واردشده در این مرور
منابع اضافی
منابع دیگر نسخه‌های منتشرشده این مرور

Altman H, Mehta D, Evenson RC, Sletten IW. Behavioral effects of drug therapy on psychogeriatric inpatients: I. chlorpromazine and thioridazine. Journal of the American Geriatrics Society 1973;21(6):241‐8.

Andrews P, Hall JN, Snaith RP. A controlled trial of phenothiazine withdrawal in chronic schizophrenic patients. British Journal of Psychiatry 1976;128:451‐5.

Bartko G, Sztaniszlav D, Olajos S, Bekesy M. Serum chlorpromazine and prolactin levels in paranoid schizophrenic patients and clinical response. Regional Symposium of the World. European Journal of Psychiatry 1988;2(2):109‐17. [PsycINFO]

Google Scholar

Borison RL, Diamond BI, Dren AT. Does sigma receptor antagonism predict clinical antipsychotic efficacy?. Psychopharmacology Bulletin 1991;27(2):103‐6.

Caffey EM, Prien RF. Practical considerations on treatment with antipsychotic preparations. Zhurnal nevropatologii i psikhiatrii imeni s. S. Korsakova 1975;75(9):1399‐401.

Google Scholar

Casey JF, Hollister LE, Klett CJ, Lasky JJ, Caffey EM. Combined drug therapy of chronic schizophrenics. Controlled evaluation of placebo, dextro‐amphetamine, imipramine, isocarboxazid and trifluoperazine added to maintenance doses of chlorpromazine. American Journal of Psychiatry 1961;117:997‐1003.

Chen L. A comparative study of EEG changes in patients treated by risperidone, chlorpromazine and clozpine. Journal of Qiqihar Medical College 2002;23(5):485‐6.

Google Scholar

Clark ML, Johnson PC. Amenorrhea and elevated level of serum cholesterol produced by a trifluoro‐methylated phenothiazine (SKF‐5354‐A). The Endocrine Society April 1960;20:641‐6.

Google Scholar

Clark ML, Ray TS, Paredes A, Costiloe JP, Chappell JS, Hagans JA, et al. Chlorpromazine in chronic schizophrenic women: I. Experimental design and effects at maximum point of treatment. Psychopharmacologia 1961;2:107‐36.

Clark M, Dubowski K, Colmore J. The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients. Clinical Pharmacology and Therapeutics 1970;11:883‐9.

Clark ML, Ray TS, Paredes A, Ragland RE, Costiloe JP, Smith CW, et al. Chlorpromazine in women with chronic schizophrenia: the effect on cholesterol levels and cholesterol‐behavior relationships. Psychosomatic Medicine 1967;29(6):634‐42. [PUBMED: 5582955]

Clark M, Dubowski K, Colmore J. The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients. Clinical Pharmacology and Therapeutics 1970;11:883‐9.

Clark ML, Kyriakopoiilos A, Ragland RE. Chlorpromazine in chronic schizophrenic women: its effect on thyroid and liver function in relation to serum cholesterol concentration. Pharmacologia Clinica 1970;2(4):227‐30.

Clark M, Dubowski K, Colmore J. The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients. Clinical Pharmacology and Therapeutics 1970;11:883‐9.

Clark ML, Huber WK, Sakata K, Fowles DC, Serafetinides EA. Molindone in chronic schizophrenia. Clinical Pharmacology and Therapeutics 1970;11(5):680‐8.

Clark ML, Kaul PN. A preliminary report on clinical response and blood levels of chlorpromazine and its sulfoxide during chlorpromazine therapy in chronic schizophrenic patients. In: Gottschalk LA, Merlis S editor(s). Pharmacokinetics of Psychoactive Drugs. New York (NY): Spectrum Publications, 1976:191‐7.

Google Scholar

Clark ML, Kaul PN, Whitfield LR. Chlorpromazine kinetics and clinical response. Psychopharmacology Bulletin 1978;14(3):43‐5.

Cooper SF, Albert JM, Hillel J, Caille G. Plasma‐level studies of chlorpromazine following the administration of chlorpromazine hydrochloride and chlorpromazine embonate in chronic schizophrenics. Current Therapeutic Research, Clinical and Experimental 1973;15(2):73‐7.

Crane GE. Tardive dyskinesia in schizophrenic patients treated with psychotropic drugs. Agressologie 1968;9(2):209‐16. [MEDLINE: 5675488; PsycINFO]

Curry SH. Antipsychotic drugs. I. chlorpromazine: pharmacokinetics, plasma levels and clinical response. In: Burrows GD, Norman T editor(s). Plasma Levels of Psychotropic Drugs and Clinical Response. New York (NY): Marcel Dekker, 1978.

Google Scholar

Curry SH. Metabolism and kinetics of chlorpromazine in relation to effect. In: Sedvall G, Uvnas B, Zotterman Y editor(s). Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics. Oxford: Pergamon Press, 1976:343‐52.

Google Scholar

Danion JM, Peretti S, Grange D, Bilik M, Imbs JL, Singer L. Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers. Psychopharmacology [Psychopharmacologia] 1992;108(3):345‐51.

Eitan N, Levin Y, Ben Artzi E, Levy A, Neumann M. Effects of antipsychotic drugs on memory functions of schizophrenic patients. Acta Psychiatrica Scandinavica 1992;85(1):74‐6.

Gibbs JJ, Wilkens B, Lauterbach CG. A controlled clinical psychiatric study of chlorpromazine. Journal of Clinical and Experimental Psychopathology 1957;18:269‐83.

Gibbs JJ, Wilkens B, Lauterbach CG. A controlled clinical psychiatric study of the drug chlorpromazine. American Journal of Psychiatry1956; Vol. 113:254‐5.

Google Scholar

Green JF, King DJ. The effects of chlorpromazine and lorazepam on abnormal antisaccade and no‐saccade distractibility. Biological Psychiatry 1998;44:709‐15.

Green JF, McElholm A, King DJ. A comparison of the sedative and amnestic effects of chlorpromazine and lorazepam. Psychopharmacology 1996;128:67‐73.

Hartley L, Henry T, Couper‐Smartt J. Chlorpromazine and serial reaction performance. British Journal of Psychology 1978;69:271‐6.

Janakiramaiah N, Channabasavanna SM, Narashimha Murthy NS. ECT‐chlorpromazine combination versus chlorpromazine alone in acutely schizophrenic patients. Acta Psychiatrica Scandinavica 1982;66(6):464‐70.

Jeste DV, Olgiati SG, Ghali AY. Masking of tardive dyskinesia with four times‐a‐day administration of chlorpromazine. Diseases of the Nervous System 1977;38(9):755‐8.

Joshi VG, Nagesh R, Eswaran S, Nagesh R, Pai M, Matthews G, et al. Vitamins B1, B6, and B12 in the adjunctive treatment of schizophrenia ‐ further studies to examine the effect of reduction of chlorpromazine dosage. Journal of Orthomolecular Psychiatry 1982;11(1):45‐9.

Google Scholar

Kalyanasundaram S, Shrikhande SA, Machado TA, Kapur RL. Single daily dose chlorpromazine therapy in psychosis. An evaluation. Acta Psychiatrica Scandinavica 1981;64(2):158‐66.

Lehmann HE, Wilson WH, Deutsch M. Minimal maintenance medication: effects of three dose schedules on relapse rates and symptoms in chronic schizophrenic outpatients. Comprehensive Psychiatry1983; Vol. 24, issue 4:293‐303. [MEDLINE: 6136389]

Google Scholar

Ota KY, Kurland AA, Rocha J, Block BA. A comparison of the relative clinical efficacy of two chlorpromazine (CPZ) preparations. Current Therapeutic Research, Clinical and Experimental 1974;16(9):1014‐21.

Pigache RM. Effects of placebo, orphenadrine, and rising doses of chlorpromazine, on PAT performance in chronic schizophrenia. A two year longitudinal study. Schizophrenia Research 1993;10(1):51‐9.

Schiele B. Comparison of low and high dosage procedures in chlorpromazine therapy. Psychiatric Quarterly 1959;33:252‐9.

Sukegawa T, Ito T, Hasegawa M, Mizuno Y, Inagaki A, Sakamoto H, et al. A randomized controlled trial on the dose reduction and simplification for polypharmacy of antipsychotics. Tottori Journal of Clinical Research 2008;1:169‐81.

Google Scholar

Sukegawa T. Implementation of appropriate administration of antipsychotics ‐ measures to reduce high‐dose multiple antipsychotics. Nihon Rinsho 2013;71(4):712‐7.

Sukegawa T. Measures to reduce high‐dose multiple antipsychotics in Japan. Seishin Shinkeigaku Zasshi 2012;114(6):696‐701.

Sukegawa T, Inagaki A, Yamanouchi Y, Inada T, Yoshio T, Yoshimura R, et al. Study protocol: safety correction of high dose antipsychotic polypharmacy in Japan. BMC Psychiatry 2014;14(1):103.

Yuan‐Guang C, Guang‐Rong X, Jing Ping Z. A study on the relationship between the chlorpromazine plasma levels and clinical response to chlorpromazine administrations in the schizophrenics. Chinese Journal of Neurology and Psychiatry 1994;27(3):153‐5.

Google Scholar

منابع اضافی

Ir a:

منابع مطالعات واردشده در این مرور
منابع مطالعات خارج‌شده از این مرور
منابع دیگر نسخه‌های منتشرشده این مرور

Adams CE, Bergman H, Irving CB, Lawrie S. Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2013, issue 11. [DOI: 10.1002/14651858.CD003082.pub3; CD003082]

Google Scholar

Adams CE, Awad G, Rathbone J, Thornley B, Soares‐Weiser K. Chlorpromazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD000284.pub3]

Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996;313:1200. [OLZ020600]

Armitage P. Statistical Methods in Medical Research. Oxford‐Edinburgh (UK): Blackwell Scientific Publications, 1971.

Barbato A. Schizophrenia and Public Health. Geneva: World Health Organization, 1998. [WHO/MSA/NAM/97.6]

Bazire S. Psychotropic Drug Directory 2014. Norwich (UK): Page Bros Ltd, 2014.

Bland JM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600.

Joint Fomulary Committee. British National Formulary. 8th Edition. London (UK): BMJ Group and Pharmaceutical Press, 2014.

Boissel JP, Cucherat M, Li W, Chatellier G, Gueyffier F, Buyse M, et al. The problem of therapeutic efficacy indices. 3. Comparison of the indices and their use [Aperçu sur la problématique des indices d'efficacité thérapeutique, 3: comparaison des indices et utilisation. Groupe d'Etude des Indices D'efficacite]. Therapie 1999;54(4):405‐11.

Bollini P. Antipsychotic drugs: is more worse? A meta analysis of the published randomised control trials. Psychological Medicine 1994;24:307‐16.

Carpenter WT, Buchanan RW. Schizophrenia. New England Journal of Medicine 1994;330(10):681‐90.

Clark M, Dubowski K, Colmore J. The effect of chlorpromazine on serum cholesterol in chronic schizophrenic patients. Clinical Pharmacology and Therapeutics 1970;11:883‐9.

David JM. Dose equivalence of the antipsychotic drugs. Journal of Psychiatric Research 1974;11:65‐9.

de Oliveira Marques L, Soares B, de Lima MS. Trifluoperazine for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2004, issue 1. [DOI: 10.1002/14651858.CD003545.pub2; CD003545]

Google Scholar

Deeks J. Issues in the selection for meta‐analyses of binary data. 8th International Cochrane Colloquium; 2000 Oct 25‐28th; Cape Town, South Africa. Cape Town, 2000.

Google Scholar

Deeks JJ, Higgins JPT, Altman DG editor(s). Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Divine GW, Brown JT, Frazer LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7:623‐9.

Dold M, Samara MT, Li C, Tardy M, Leucht S. Haloperidol versus first‐generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2015, issue 1. [DOI: 10.1002/14651858.CD009831.pub2; CD009831]

Google Scholar

Donner A, Klar N. Issues in the meta‐analysis of cluster randomized trials. Statistics in Medicine 2002;21:2971‐80.

Egger M, Davey‐Smith G, Schneider M, Minder CSO. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;13:629‐34.

Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9.

Endicott J, Spitzer R, Gleiss J, Cohen CJ. The global assessment scale. A procedure to measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 1976;33:766‐71.

Essali A, Al‐Haj HN, Li C, Rathbone J. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2009, issue 1. [DOI: 10.1002/14651858.CD000059.pub2; CD000059]

Google Scholar

Fenton M, Rathbone J, Reilly J. Thioridazine for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2007, issue 3. [DOI: 10.1002/14651858.CD001944.pub2; CD001944]

Google Scholar

Furukawa TA, Barbui C, Cipriani A, Brambilla P, Watanabe N. Imputing missing standard deviations in meta‐analyses can provide accurate results. Journal of Clinical Epidemiology 2006;59(7):7‐10.

Geddes JR, Freemantle N, Harrison P, Bebbington PE. Atypical antipsychotics in the treatment of schizophrenia: a systematic overview and meta‐regression analysis. BMJ 2000;321:1371‐6.

Gulliford MC, Ukoumunne OC, Chinn S. Components of variance and intraclass correlations for the design of community‐based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149:876‐83.

Guy W. Early Clinical Drug Evaluation (ECDEU) Assessment Manual for Psychopharmacology. Washington, DC: National Institute of Mental Health, 1976:217‐22.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60.

Higgins, JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Chichester (UK): John Wiley & Sons, 2008.

Higgins JPT, Green S, editor(s). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Higgins JPT, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Hunter R, Kennedy E, Song F, Gadon L, Irving CB. Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2003, issue 2. [DOI: 10.1002/14651858.CD000440; CD000440]

Google Scholar

Hutton JL. Number needed to treat and number needed to harm are not the best way to report and assess the results of randomised clinical trials. British Journal of Haematology 2009;146(1):27‐30.

Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323:42‐6.

Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda (NY): Multi‐Health Systems, 1986.

Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA. Trifluoperazine versus placebo for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2014, issue 1. [DOI: 10.1002/14651858.CD010226.pub2; CD010226]

Google Scholar

Komossa K, Rummel‐Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2011, issue 1. [DOI: 10.1002/14651858.CD006626.pub2; CD006626]

Google Scholar

Kumar A, Strech D. Zuclopenthixol dihydrochloride for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2005, issue 4. [DOI: 10.1002/14651858.CD005474; CD005474]

Google Scholar

Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low‐potency conventional antipsychotics: a systematic review and meta‐analysis. Lancet 2003;361:1581‐9.

Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean?. Schizophrenia Research 2005;79(2‐3):231‐8. [PUBMED: 15982856]

Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel R. Clinical implications of brief psychiatric rating scale scores. British Journal of Psychiatry 2005;187:366‐71. [PUBMED: 16199797]

Leucht C, Kitzmantel M, Kane J, Leucht S, Chua WL. Haloperidol versus chlorpromazine for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2008, issue 1. [DOI: 10.1002/14651858.CD004278.pub2; CD004278]

Google Scholar

Lipka LJ, Lathers CM, Roberts J. Does chlorpromazine produce cardiac arrhythmia via the central nervous system?. Journal of Clinical Pharmacology 1988;28(11):968‐83.

Magalhães Pedro VS, Dean O, Andreazza AC, Berk M, Kapczinski F. Antioxidant treatments for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2016, issue 2. [DOI: 10.1002/14651858.CD008919.pub2; CD008919]

Google Scholar

Marshall M, Lockwood A, Bradley C, Adams C, Joy C, Fenton M. Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. British Journal of Psychiatry 2000;176:249‐52.

Statistics on Mental Health. Factsheet. Mental Health Foundation2014.

Overall JE, Gorham DR. The brief psychiatric rating scale. Psychological Reports 1962;10:799‐812.

Prien RF, DeLong SL, Cole JO, Levine J. Ocular changes occurring with prolonged high dose chlorpromazine therapy. Results from a collaborative study. Archives of General Psychiatry 1970;23(5):464‐8. [MEDLINE: 5478574; MEDLINE: 71030994]

Rummel‐Kluge C, Kissling W, Leucht S. Antidepressants for the negative symptoms of schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2006, issue 3. [DOI: 10.1002/14651858.CD005581.pub2; CD005581]

Google Scholar

Saha KB, Bo L, Zhao S, Xia J, Sampson S, Zaman RU. Chlorpromazine versus atypical antipsychotic drugs for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2016, issue 4. [DOI: 10.1002/14651858.CD010631.pub2; CD010631]

Google Scholar

Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2008:359‐83.

Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Seeman P. Atypical antipsychotics: mechanism of action. Canadian Journal of Psychiatry 2002;47(1):27‐38.

Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavacia 1970;212:11‐9.

Sterne JAC, Egger M, Moher D, editor(s). Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Intervention. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Tardy M, Huhn M, Kissling W, Engel RR, Leucht S. Haloperidol versus low‐potency first‐generation antipsychotic drugs for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2014, issue 7. [DOI: 10.1002/14651858.CD009268.pub2; CD009268]

Google Scholar

Tardy M, Dold M, Engel RR, Leucht S. Trifluoperazine versus low‐potency first‐generation antipsychotic drugs for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2014, issue 7. [DOI: 10.1002/14651858.CD009396.pub2; CD009396]

Google Scholar

Turner T. Chlorpromazine: unlocking psychosis. BMJ 2007;334(Suppl 1):s7. [PUBMED: 17204765]

Tuunainen A, Wahlbeck K. Newer atypical antipsychotic medication versus clozapine for schizophrenia. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2000, issue 2. [DOI: 10.1002/14651858.CD000966; CD000966]

Google Scholar

Ukoumunne OC, Gulliford MC, Chinn S, Sterne JAC, Burney PGJ. Methods for evaluating area‐wide and organisation‐based intervention in health and health care: a systematic review. Health Technology Assessment 1999;3(5):1‐75.

Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS, Lipska BK, et al. Prefrontal neurons and the genetics of schizophrenia. Biological Psychiatry 2001;50(11):825‐44.

Weinberger DR, Harrison PJ. Schizophrenia. 3rd Edition. Chichester (UK): Wiley‐Blackwell, 2011.

World Health Organisation. The World Health Report 2001 Mental Health: New Understanding, New Hope. www.who.int/whr/2001/en/ (accessed 20 January 2017).

World Health Organisation. WHO Model List of Essential Medicines. apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1. 18th (April 2013) (accessed 20 January 2017).

Xia J, Adams CE, Bhagat N, Bhagat V, Bhoopathi P, El‐Sayeh H, et al. Loss to outcomes stakeholder survey: the LOSS study. Psychiatric Bulletin 2009;33(7):254‐7.

منابع دیگر نسخه‌های منتشرشده این مرور

Ir a:

منابع مطالعات واردشده در این مرور
منابع مطالعات خارج‌شده از این مرور
منابع اضافی

Liu X, De Haan S. Chlorpromazine dose for people with schizophrenia. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD007778]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

Chouinard 1976

Methods	Allocation: randomised ‐ block randomised into 11 groups. Blindness: double‐blind. Duration: 8 weeks (after 2 weeks of stabilisation).
Participants	Diagnosis: schizophrenia. N = 55. Age: 20‐57 (mean 38.5). Sex: 30 males, 25 females. History: a primary hospital diagnosis of schizophrenia confirmed by the research psychiatrist; presence of two or more of the following symptoms or behaviours: thought or speech disturbances, catatonic motor behaviour, paranoid ideation, hallucinations, delusional thinking other than paranoid, blunted or inappropriate affect and disturbance of social behaviour and interpersonal relations. Excluded: patients with physical illness, childhood schizophrenia, chronic or acute brain syndrome, mental deficiency (IQ below 70), alcoholism, epilepsy or drug addiction.
Interventions	1. Chlorpromazine: dose 600 mg/day. N = 11. 2. Chlorpromazine: dose 300 mg/day. N = 11. 3. α‐methyldopa: dose 250 mg/day + Chlorpromazine: dose 300 mg/day. N = 11. 4. α‐methyldopa: dose 500 mg/day + Chlorpromazine: dose 300 mg/day. N = 11. 5. α‐methyldopa: dose 750 mg/day + Chlorpromazine: dose 300 mg/day. N = 11. interventions started after 2 weeks of fixed doses of 300 mg/day CPZ
Outcomes	Leaving the study early. Adverse effects. Mental state: BPRS. Unable to use ‐ Mental state: IMPS (reported numbers of patients and mean, no SD or P values). Laboratory tests (physiological). Blood pressure (physiological). Pulse rate (physiological).
Notes	Lost to follow‐up: 1 patient lost during 5th week, assumed not treatment related. Reason given: he had a habit of leaving the hospital without authorisation. Unclear which treatment group he belonged to. Plan to assume that from one of the α‐methyldopa groups (3/5 chance of this).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "within a block: patients were then randomly assigned" pp119, p3. Comment: Block randomised, no further details.
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "double‐blind conditions", "identical‐appearing tablets...administered three times a day" pp119, p6. Comment: probably done (double, tablets of identical appearance, same amount of tablets and treatment scheme to all patients).
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "one male patient left the hospital without authorization during the 5th week of treatment" pp120, p4. Comment: 1 person lost to follow‐up, data at the time of loss (5th week) reported as end data.
Selective reporting (reporting bias)	Low risk	All outcomes reported.
Other bias	Low risk	Quote: "This study was supported in part by the Medical Research Council of Canada and by an FCAC grant (Financial Consumer Agency of Canada, Quebec)" pp125,p3.

Clark 1972

Methods	Allocation: randomised ‐ block randomised but not specified how. Blindness: double‐blind. Duration: 24 weeks (after 12 weeks of 'dry‐out').
Participants	Diagnosis: schizophrenia. N = 71.* Age: 23‐69 (mean 43.7). Sex: women. History: chronic schizophrenia. Excluded: bad physical health with complicating organic illness or known brain damage.
Interventions	1. Chlorpromazine: dose 150 mg/day. N = 16. 2. Chlorpromazine: dose 300 mg/day. N = 15. 3. Chlorpromazine: dose 600 mg/day**. N = 17. 4. Placebo. N = 17.
Outcomes	Adverse effects. Unable to use ‐ Leaving the study early (6 people lost to follow‐up ‐ 1 rash and anaemia, 1 granulocytosis, 2 left the hospital, 2 requisite surgery ‐ unclear from which group). Mental state: IMPS, BPRS (N and mean, no SD). Global state: CGI‐SI, OBRS, CGI‐I (N and mean, no SD). Blood pressure, body temperature, pulse, EEG, serum cholesterol (physiological). Body weight (N and mean, no SD). Service use: duration of hospitalisation (N and mean, no SD).
Notes	* Initially 71 people randomised but people lost to follow‐up and unclear from which group, ‐ so outcomes reported on only those who completed. ** Initial low doses increased over 10 days to final fixed dose level. Lost to follow‐up: The number of participants requiring additional sedation with chloral hydrate or a barbiturate on more than 5 occasions during the 24 weeks of treatment were 5 in the PL group, 4 in the CPZ‐150 group, 2 in the CPZ‐300 group and 1 in the CPZ‐600 group. Study #4 of 6 separate studies reported in paper.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "each treatment group was first subdivided by age at the time of beginning the study" pp479, p6 Comment: Block randomisation, no details.
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "double‐blind study" pp479, p5; "all patients received the same volume of medication (10 mL twice daily) but in different concentration" pp262, p1 Comment: probably done.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: no quote. Comment: 8% loss to follow‐up ignored in analyses.
Selective reporting (reporting bias)	High risk	Quote: "one subject dropped out because of rash and anaemia, one because of agranulocytosis, two because of elopement from the hospital and two because of requisite surgery" pp263, p2. Comment: clinical outcomes reported by group of allocation, leaving the study not reported by group of allocation.
Other bias	Unclear risk	Quote: "The authors are grateful to Mr. Robert C. Zwahlen of Smith, Kline and French Laboratories for generous supplies of medication for this study" pp269, p5. Comment: we are unclear if this support went beyond supply of medication.

Prien 1968

Methods	Allocation: randomised. Blindness: double‐blind. Duration: 24 weeks.
Participants	Diagnosis: schizophrenia. N = 838. Age:19‐55 (mean 41.6). Sex: about 50% males, 50% females. History: chronic schizophrenia. Excluded: organic brain disease (including lobotomy), mental deficiency (IQ < 70), medical conditions constraining use of high doses.
Interventions	1. Chlorpromazine: dose 300 mg/day. N = 208. 2. Chlorpromazine: dose 2000 mg/day. N = 208. 3. Conventional treatment (doctor's choice). N = 210. 4. Placebo. N = 212. In gradual increasing doses, reaching the maximal doses after 45 days.
Outcomes	Global state: GIS, GSIS, GAS, relapse. Adverse effects. Leaving the study early. Unable to use ‐ Global state: relapse (only data of placebo group reported), failure of therapy (not specified for the entire group of low dose CPZ). Service outcomes: DRI (no data specified). Mental state: IMPS (no data specified). Behaviour: NOSIE (no data specified). Ocular changes (lens change, corneal change, skin changes, photosensitivity, visual acuity).
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "randomly assigned to four treatment groups" pp483, p5. Comment: no details provided.
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "The low dose and placebo group also received liquid concentrate, on a double‐blind basis" pp483, p6. Comment: identical liquid administration. Blinding probably done.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up: 51 of high dose group (41 disabling adverse effects, 10 other), 31 of low‐dose group (4 disabling adverse effects, 27 other).
Selective reporting (reporting bias)	High risk	No SD for several outcomes, several outcomes not reported (see above). Only data of patients evaluated by same rater at pretreatment and termination reported in general state, CGI‐SI (aka GSIS) ‐ reviewers equally divided remaining patients over low‐ and high‐dose groups, assuming similar rates of adverse effects for those who did have data recorded (see Methods, Missing data).
Other bias	Low risk	Quote: "This investigation was supported by Public Health Service grants...from the National Institute of Mental Health, and Public Health Service" pp494 ,p6.

Wode‐Helgodt 1978

Methods	Allocation: randomised. Blindness: double‐blind. Duration: 4 weeks (after 7 days placebo).
Participants	Diagnosis: psychosis of schizophrenic type. N = 48. Age: 19‐57 years, mean ˜30 years. Sex: 20 males, 28 females. History: emergency ward patients. Presence of thought disorder, delusions or auditory hallucinations. Excluded: antipsychotic drug treatment during month preceding study, presence of complicating somatic illness or organic brain disease, alcoholism or drug abuse, manic or depressive psychosis, borderline cases, those admitted with confusional state when psychotic symptoms did not persist when confusion cleared, unable to co‐operate, showing severe suicidal or aggressive impulses.
Interventions	1. Chlorpromazine: dose 200 mg/day. N = 15. 2. Chlorpromazine: dose 400 mg/day. N = 18. 3. Chlorpromazine: dose 600 mg/day. N = 15. Additional medication: Nitrazepam 5‐10 mg (N = 30) for sleep, diazepam 5 mg (N = 18) for daytime sedation ‐ not reported by group. Commented as: results not deviating significantly from those of the remaining patients, therefore additional medication was disregarded in final evaluation.
Outcomes	Leaving the study early. Adverse effects: modified Simpson and Angus. Unable to use ‐ Mental state: CPRS (presented in graphical form, unable to extract data). General functioning: GRS (presented in graphical form, unable to extract data). Prolactin levels in CSF (physiological). Prolactin levels in plasma (physiological). Total prolactin, FSH, LH, TSH and oestradiol in CSF (physiological). Total prolactin, FSH, LH, TSH and oestradiol in plasma (physiological). Monoamine metabolite (HVA, MOPEG and 5‐HIAA) levels in CSF (physiological).
Notes	One man had diabetes mellitus and was treated with insulin (64 IU daily). Commented that the results obtained with this patient were similar to those seen in the rest of the group.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “A research assistant not involved in the project attempted to assign an equal number of men and women to each dose using the technique of restricted randomisation (Armitage (1971))” pp152, p1. Comment: Stratified randomisation attempted. Armitage 1971 was referenced with no further explanation.
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: “For drug administration the “double‐dummy technique” was used, i.e. every patient received the same total number of tablets containing CPZ or placebo. The appearance of the placebo tablets was identical to those containing CPZ” pp152, p1. Comment: double‐dummy technique probably done, same tablet numbers and shape.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Four patients dropped out before the 2‐week evaluation since dose had to be adjusted for ethical reasons. Thus a man and a woman on 600mg showed extreme somnolence, requiring dose reduction. In a man on 400mg and a woman on 200mg the doses were increased because of insufficient effect on the severe psychosis. Another six patients dropped out after the 2‐week, but the 4‐week, evaluation. In a woman and a man on 400mg, the dose was increased due to insufficient antipsychotic effect. A man on 400mg who was markedly improved clinically was omitted because of severe elevation of transaminase levels. Another man on 200mg and a woman on 400mg were also both quite well and insisted on being discharged from the hospital. A woman on 600mg refused further medication" pp154,p5. Comment: loss to follow‐up described from each group in detail.
Selective reporting (reporting bias)	High risk	For some scales only graphs without numeric data.
Other bias	Low risk	Quote: “This investigation was supported by grants from the Swedish Medical Research Council (No. 21X‐02291, 14X‐03560), National Institutes of Health, Bethesda, Maryland, and USA (MH 27254‐01), F.Hoffmann‐La Roche, Basle, Switzerland, ‘Forenade Liv’ Mutual Group Life Insurance Company, Stockholm, Sweden, Svenska Lakaresallskapet: Anton och Dorothea Bexelius Minnesfond, Bror Gadelius Minnesfond, Karolinska Institutets Fonder, AB Leo, Sweden, and Magnus Bergvalls Stiftelse” pp171, p2. Comment: publication bias unlikely.

Xu 2009

Methods	Allocation: randomised (divided into large‐dose group and small‐dose group according to the odd‐even number). Blindness: Not mentioned. Duration: 8 weeks.
Participants	Diagnosis: CCMD ‐3. N = 120. (60 in CPZ group, 60 in clozapine group). Age: 18‐60 years, mean ˜ 33 years. Sex: 31 male, 29 female. History: inpatients. Excluded: severe physical diseases, alcohol and substance dependence; pregnancy and lactation.
Interventions	1. Medium dose CPZ: dose titrated between 425 mg ‐ 600 mg/day (mean 494.1 mg/day). 2. Low dose CPZ: dose titrated between 250 mg ‐ 400 mg/day (mean 338.3 mg/day). 3. Medium dose clozapine. 4. Low dose clozapine. *Other antipsychotics, antidepressants, Antimanic Drugs and MECT were not allowed during the treatment. Benzhexol, sedatives and tranquillizers and β blocker were used if necessary.
Outcomes	Global state: CGI‐SI. Mental state: PANSS. Adverse effects.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised. No detailed information was described in the study.
Allocation concealment (selection bias)	Unclear risk	Not mentioned. No detailed information was described in the study.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not mentioned. No detail information was described in the study.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All outcomes were reported.
Selective reporting (reporting bias)	Low risk	No selective reporting was found.
Other bias	Low risk	Not obvious.

BPRS ‐ Brief Psychiatric Rating Scale
CCMD‐3 ‐ Chinese Classification of Mental Disorders Version 3
CGI‐I ‐ Clinical Global Impression ‐ Improvement scale
CGI‐SI ‐ Clinical Global Impression ‐ Severity of Illness scale
CPRS ‐ Comprehensive Psychopathological Rating Scale
CPZ ‐ Chlorpromazine
CSF ‐ cerebrospinal fluid
DRI ‐ Discharge Readiness Inventory
EEG ‐ electroencephalogram
FSH ‐ follicle‐stimulating hormone
GIS ‐ Global Improvement Scale (aka CGI‐I)
GRS ‐ Global Rating Scale
GSIS ‐ Global Severity of Illness Scale (aka CGI‐SI)
GAS ‐ Global Assessment Scale
IMPS ‐ Inpatient Multidimensional Psychiatric Scale
IU ‐ international unit
LH ‐ luteinizing hormone
NOSIE ‐ Nurse's Observation Scale for Inpatient Evaluation
OBRS ‐ Oklahoma Behaviour Rating Scale
PANSS‐ Positive And Negative Syndrome Scale
TSH ‐ thyroid‐stimulating hormone

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Altman 1973	Allocation: randomised (times 3 factorial design). Participants: psychogeriatric inpatients (total = 151, 81 completed with schizophrenia). Interventions: CPZ vs thioridazine and bed time dose vs day time fractional doses and 30 mg vs 60 mg vs 90 mg vs 120 mg. All CPZ doses ‘low’ according to definitions in this review. Outcomes: leaving early, 'response', behaviour (needing chlordiazepoxide, MIBS), side effects ‐ no usable data, all reported for total group and not for people with schizophrenia, all regression scores rather than averages or binary outcomes.
Andrews 1976	Allocation: randomised. Participants: people with schizophrenia. Interventions: CPZ 50‐100 mg/day vs CPZ 150‐200 mg/day vs CPZ >200 mg/day. Outcomes: unable to use ‐ 7 patients received between 300 mg and 4450 mg ‐ data not presented in such a way to use within this review.
Bartko 1988	Allocation: randomised. Participants: people with schizophrenia. Interventions: CPZ 300 mg/day vs CPZ 450 mg/day vs CPZ 700 mg/day. Outcomes: data reported by CPZ serum levels, not by original group of randomisation.
Borison 1991	Allocation: randomised, "double‐blind". Participants: people with schizophrenia. Interventions: rimcazole 20 mg ‐ 80 mg/day vs rimcazole 100 mg ‐ 400 mg/day vs CPZ 400 mg ‐1600 mg/day vs placebo.
Caffey 1975	Allocation: "double‐blind", randomisation not stated. Participants: people with schizophrenia. Interventions: study 1‐ continuous use of antipsychotics vs antipsychotics 5 days/week vs antipsychotics 4 days/week. Study 2 ‐ antiparkinsonian treatment vs placebo as an adjunct to antipsychotics.
Casey 1961	Allocation: randomised, "double‐blind". Participants: men with schizophrenia who are physically healthy but apathetic and withdrawn. Interventions: Combination of CPZ with: dextroamphetamine vs isocarboxazid vs trifluoperazine vs imipramine vs placebo, not dose.
Chen 2002	Allocation: not stated (possibly CCT). Participants: people with schizophrenia. Interventions: risperidone vs chlorpromazine vs clozapine.
Clark 1960	Allocation: not randomised, case series.
Clark 1961	Allocation: randomised (table of random numbers). Participants: people with schizophrenia. Interventions: Given different doses to each other, often changing over the weeks and potentially sliding between dosage categories.
Clark 1967	Allocation: randomised, table of random numbers (Study #1 and #2 of Clark 1970). Participants: women with chronic schizophrenia. Interventions: placebo vs rapidly increasing doses to a maximum of chlorpromazine 800 mg/day, not comparing doses.
Clark 1970a	Allocation: randomised, "double‐blind" (Study #3 of Clark 1970). Participants: women with chronic schizophrenia. Interventions: placebo vs rapidly increasing doses to the point of toxicity or to a maximum of CPZ 800 mg/day, not comparing doses.
Clark 1970b	Allocation: randomised, "double‐blind" (Study #6 of Clark 1970). Participants: people with chronic schizophrenia. Interventions: placebo vs chlorpromazine 800 mg/day vs clopenthixol, not comparing doses.
Clark 1978	Allocation: randomised. Participants: people with schizophrenia. Interventions: CPZ 200 mg/m²/day vs CPZ 600 mg/m²/day. Outcomes: unable to use ‐ one paper reported outcomes for 4/25 people, second paper reports data on blood pressure ‐ unable to present.
Cooper 1973	Allocation: not randomised, cross‐over investigating plasma levels.
Crane 1968	Allocation: randomised, cross‐over. Participants: people with schizophrenia. Interventions: different doses of CPZ given for 6 months, then 6 months of different drugs 'as prescribed'. Outcome: no data available before cross‐over, 60% loss to follow‐up.
Curry 1976	Allocation: not randomised, case series investigating plasma levels.
Danion 1992	Allocation: randomised. Participants: healthy people, not people with schizophrenia.
Eitan 1992	Allocation: "assigned", "double‐blind", cross‐over, implied randomisation. Participants: people with schizophrenia. Interventions: chlorpromazine, thioridazine, trifluoperazine, haloperidol, placebo (sodium bicarbonate) administered at 90‐min intervals ‐ order of administration randomised, not dose.
Gibbs 1956	Allocation: randomised. Participants: people with schizophrenia. Interventions: chlorpromazine 75 mg/day ‐125mg/day vs chlorpromazine 150 mg/day ‐ 450 mg/day ‐ not clearly fitting within the categories pre‐stated in protocol for low and medium dose.
Green 1996	Allocation: randomised, cross‐over. Participants: healthy people, not people with schizophrenia.
Hartley 1978	Allocation: all people received the 3 drug treatments, "order determined by Latin Square". Participants: healthy men, not people with schizophrenia.
Janakiramaiah 1982	Allocation: randomised. Participants: people with schizophrenia. Interventions: CPZ 300 mg/day vs CPZ 500 mg/day. Outcomes: no usable data ‐ BPRS score (no SD), incomplete data not addressed, movement disorder adverse effects, global impression both assessed ‐ but no data.
Jeste 1977	Allocation: randomised, crossover. Participants: outpatients with schizophrenia diagnosed with persistent dyskinesia (total = 3). Interventions: schedule A (weeks 1 & 2(0), 3 & 4(four times a day), 5(0), 6 & 7(once daily), 8(0), 9 &10 (four times a day), 11(0), 12 & 13(once daily), 14(0).) vs schedule B (weeks 1& 2(0), 3 & 4(once daily), 5(0), 6 & 7(once daily), 8(0), 9 & 10(once daily), 11(0), 12 &13 (four times a day).), not dose.
Joshi 1982	Allocation: randomised, "double‐blind". Participants: people with schizophrenia (untreated Acute Schizophrenic Psychosis). Interventions: 4 groups of varying CPZ doses with daily injection of vitamin preparation (containing B1, B6 and B12) vs placebo.
Kalyanasundaram 1981	Allocation: randomised, "double‐blind". Participants: acutely psychotic people. Interventions: bed time dose of CPZ vs day time fractional doses of CPZ.
Lehmann 1983	Allocation: randomised, but the procedure was not entirely successful (top p295). Participants: hospitalised chronic psychotic people. Interventions: high vs low chlorpromazine equivalent dosages ‐ unclear what antipsychotic drugs were used.
Ota 1974	Allocation: randomised, "double‐blind", cross‐over. Participants: hospitalised chronic psychotic people. Interventions: CPZ preparation A vs CPZ preparation B. Comparison of different brands, not different doses.
Pigache 1993	Allocation: "blindness" achieved by randomisation of duration of treatment time periods, not dose.
Schiele 1959	Allocation: "carefully matched". Participants: people with serious mental illnesses. Interventions: high vs low dose CPZ, dose of CPZ adapted to patients response, not fixed dose.
Sukegawa 2008	Allocation: randomised. Participants: inpatients with schizophrenia. Interventions: all participants given 3 or more antipsychotics with total dosage more than 1500 mg CPZ equivalence (mg CP), RAS group vs control group with continuation of polypharmacy, multiple antipsychotics.
Sukegawa 2012	Allocation: randomised. Participants: people with schizophrenia. Interventions: all participants undergo dose reduction of antipsychotic drugs (for low potency drugs: dose decreased with 25 mg CP or lower per week. For high potency drugs: dose decreased with 50 mg CP or lower per week), multiple antipsychotics.
Sukegawa 2014	Allocation: randomised. Participants: people with schizophrenia, aged 20 or over. Interventions: control group vs dose reduction (dose decreased to 80% or less than the initial dose over 3‐6 months according to SCAP method), multiple antipsychotics.
Yuan‐Guang 1994	Allocation: randomised. Participants: inpatients with schizophrenia. Interventions: CPZ 100 mg (three time a day) vs CPZ 100 mg (three time a day) + trihexyphenidyl 2 mg (three time a day) vs CPZ 200 mg (three time a day) + trihexyphenidyl 2 mg (three time a day), both CPZ doses ‘low’ according to definitions in this review.

CPZ ‐ Chlorpromzine
MIBS ‐ Missouri Inpatient Behaviour Scale
CCT ‐ Controlled clinical trial
BPRS ‐ Brief Psychiatric Rating Scale

RAS ‐ Reduction and Simplification of Antipsychotics
mg CP ‐ chlorpromazine equivalence
SCAP ‐ Safety Correction of High Dose Antipsychotic Polypharmacy

Data and analyses

Open in table viewer

Comparison 1. CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1. Not improved ‐ short term (CGI‐SI) Show forest plot	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.28, 2.44]
Open in figure viewer Analysis 1.1 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 1 Global state: 1. Not improved ‐ short term (CGI‐SI).
2 Global state: 2. Requiring additional medication (sedation with chloral hydrate or a barbiturate > 5 times) ‐ medium term Show forest plot	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	3.09 [0.40, 23.64]
Open in figure viewer Analysis 1.2 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 2 Global state: 2. Requiring additional medication (sedation with chloral hydrate or a barbiturate > 5 times) ‐ medium term.
3 Leaving the study early Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.3 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 3 Leaving the study early.
3.1 any reason	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.32, 3.55]
3.2 adverse effects	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.02, 2.32]
3.3 inefficacy of treatment	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	4.24 [0.24, 74.01]
3.4 other reason	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.09, 9.27]
4 Mental state: 1a. Average endpoint score (BPRS total, high = poor) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.4 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 4 Mental state: 1a. Average endpoint score (BPRS total, high = poor).
4.1 anxious depression	1	22	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.35, 0.15]
4.2 thinking disturbance	1	22	Mean Difference (IV, Fixed, 95% CI)	2.60 [‐0.24, 5.44]
4.3 withdrawal retardation	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐3.76, ‐0.24]
5 Mental state: 1b. Average endpoint score (PANSS total and subscores, high = poor) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.5 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 5 Mental state: 1b. Average endpoint score (PANSS total and subscores, high = poor).
5.1 negative	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐2.34, 2.00]
5.2 positive	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.24 [‐1.98, 1.50]
5.3 total	1	60	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐5.39, 6.11]
6 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.6 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 6 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms.
6.1 akathisia ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.28, 6.68]
6.2 akinesia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
6.3 dystonia ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.05, 1.29]
6.4 gait disturbance ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.11, 1.17]
6.5 muscle tension ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.03, 0.67]
6.6 rigidity ‐ elbow ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.21, 1.31]
6.7 rigidity ‐ unspecified ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 14.05]
6.8 tremor ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.17, 1.10]
6.9 unspecified extrapyramidal symptoms ‐ short term	2	108	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.30, 0.74]
6.10 unspecified extrapyramidal symptoms ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.26 [0.05, 1.27]
7 Adverse effects: 2. Anticholinergic Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 7 Adverse effects: 2. Anticholinergic.
7.1 blurred vision ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.06, 1.63]
7.2 ejaculation disturbance ‐ short term	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 erectile disturbance ‐ short term	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 constipation ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [0.42, 7.99]
7.5 constipation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
7.6 salivation ‐ dry mouth ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.58, 2.34]
7.7 salivation ‐ too much ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.00, 1.85]
7.8 tachycardia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
7.9 urinary disturbance/trouble starting urination ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.37, 24.58]
8 Adverse effects: 3. Cardiovascular Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 8 Adverse effects: 3. Cardiovascular.
8.1 electrocardiogram abnormal ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.05, 0.94]
8.2 orthostatic symptoms (faint, dizzy, weak) ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.21, 18.98]
8.3 orthostatic symptoms ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
8.4 tachycardia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
8.5 vertigo ‐ short term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.21, 5.07]
9 Adverse effects: 4. Central nervous system ‐ other than extrapyramidal symptoms Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 9 Adverse effects: 4. Central nervous system ‐ other than extrapyramidal symptoms.
9.1 depression ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 drowsiness ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.47, 2.14]
9.3 EEG abnormal ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.33, 1.82]
9.4 head feels heavy ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.02, 1.34]
9.5 headache ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	2.35 [0.12, 46.22]
9.6 sedation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.05, 0.55]
9.7 somnolence ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.59, 2.08]
9.8 vertigo ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.19, 4.43]
10 Adverse effects: 5. Dermatological Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.10 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 10 Adverse effects: 5. Dermatological.
10.1 dermatitis ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
10.2 rash ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.39, 4.62]
10.3 rash ‐ 'photosensitivity: erythema' ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.03, 7.74]
11 Adverse effects: 6. Endocrine and metabolic Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.11 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 11 Adverse effects: 6. Endocrine and metabolic.
11.1 amenorrhoea ‐ short term	1	28	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.03, 6.74]
11.2 lactation ‐ short term	1	28	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.01, 3.73]
11.3 metrorrhagia ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 4.11]
12 Adverse effects: 7. Gastrointestinal Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.12 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 12 Adverse effects: 7. Gastrointestinal.
12.1 constipation ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [0.42, 7.99]
12.2 constipation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
12.3 unspecified ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.27, 93.55]
13 Adverse effects: 8. Genitourinary Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.13 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 13 Adverse effects: 8. Genitourinary.
13.1 urinary disturbance/trouble starting urination ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.37, 24.58]
14 Adverse effects: 9. Haematological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.14 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 14 Adverse effects: 9. Haematological.
14.1 agranulocytosis ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
14.2 anaemia ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
15 Adverse effects: 10. Hepatological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.15 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 15 Adverse effects: 10. Hepatological.
15.1 abnormal liver function ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.33, 5.45]
16 Adverse effects: 11. Others Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.16 Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 16 Adverse effects: 11. Others.
16.1 agitation and restlessness ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
16.2 excitement ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 14.05]
16.3 restlessness, insomnia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.22, 2.60]

Open in table viewer

Comparison 2. CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Not improved, severely ill, relapse (GAS) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 1 Global state: Not improved, severely ill, relapse (GAS).
1.1 no clinically important improvement	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [1.01, 1.25]
1.2 severely ill	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.96, 1.24]
1.3 relapse	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	2.25 [1.17, 4.32]
2 Leaving the study early Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 2 Leaving the study early.
2.1 any reason	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.40, 0.89]
2.2 adverse effects	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.03, 0.26]
2.3 death	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 8.14]
2.4 deterioration of behaviour	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	2.7 [1.34, 5.44]
3 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.3 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 3 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms.
3.1 akathisia	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.55, 1.83]
3.2 dystonia	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.02, 0.45]
3.3 parkinsonian reaction	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.30, 0.90]
3.4 required antiparkinsonian medication	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.26, 0.59]
3.5 unspecified	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.32, 0.59]
4 Adverse effects: 2. Anticholinergic symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.4 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 4 Adverse effects: 2. Anticholinergic symptoms.
4.1 blurred vision	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.14]
4.2 constipation	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.09, 0.79]
4.3 salivation ‐ too little (dry mouth)	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.07, 0.61]
4.4 salivation ‐ too much	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.04, 0.90]
4.5 urinary disturbance	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
5 Adverse effects: 3. Central nervous system ‐ other than extrapyramidal symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.5 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 5 Adverse effects: 3. Central nervous system ‐ other than extrapyramidal symptoms.
5.1 drowsiness	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.27, 0.57]
5.2 seizures	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.04, 0.74]
6 Adverse effects: 4. Cardiovascular Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.6 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 6 Adverse effects: 4. Cardiovascular.
6.1 dizziness, faintness	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.3 [0.16, 0.56]
6.2 peripheral oedema	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.07, 1.63]
6.3 syncope	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
7 Adverse effects: 5. Dermatological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.7 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 7 Adverse effects: 5. Dermatological.
7.1 photosensitivity	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.03, 0.24]
7.2 rashes, itching	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.03, 0.58]
8 Adverse effects: 6. Gastrointestinal Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.8 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 8 Adverse effects: 6. Gastrointestinal.
8.1 constipation	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.09, 0.79]
8.2 diarrhoea	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
8.3 nausea, vomiting	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.19, 2.33]
9 Adverse effects: 7. Genitourinary Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.9 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 9 Adverse effects: 7. Genitourinary.
9.1 urinary disturbance	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
10 Adverse effects: 8. Others Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.10 Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 10 Adverse effects: 8. Others.
10.1 occular ‐ any lens/corneal opacities	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.23, 0.52]
10.2 occular ‐ corneal changes only	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.07 [0.02, 0.30]
10.3 occular ‐ lens changes only	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.88, 3.46]
10.4 occular ‐ lens and corneal changes	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.02, 0.26]
10.5 nasal congestion	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.14, 7.03]

Figure 1

Chlorpromazine structure

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Study flow diagram

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 1 Global state: 1. Not improved ‐ short term (CGI‐SI).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 2 Global state: 2. Requiring additional medication (sedation with chloral hydrate or a barbiturate > 5 times) ‐ medium term.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 3 Leaving the study early.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 4 Mental state: 1a. Average endpoint score (BPRS total, high = poor).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 5 Mental state: 1b. Average endpoint score (PANSS total and subscores, high = poor).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 6 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 7 Adverse effects: 2. Anticholinergic.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 8 Adverse effects: 3. Cardiovascular.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 9 Adverse effects: 4. Central nervous system ‐ other than extrapyramidal symptoms.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.10

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 10 Adverse effects: 5. Dermatological.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.11

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 11 Adverse effects: 6. Endocrine and metabolic.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.12

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 12 Adverse effects: 7. Gastrointestinal.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.13

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 13 Adverse effects: 8. Genitourinary.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.14

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 14 Adverse effects: 9. Haematological.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.15

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 15 Adverse effects: 10. Hepatological.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.16

Comparison 1 CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day), Outcome 16 Adverse effects: 11. Others.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 1 Global state: Not improved, severely ill, relapse (GAS).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 2 Leaving the study early.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 3 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 4 Adverse effects: 2. Anticholinergic symptoms.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 5 Adverse effects: 3. Central nervous system ‐ other than extrapyramidal symptoms.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 6 Adverse effects: 4. Cardiovascular.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.7

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 7 Adverse effects: 5. Dermatological.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.8

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 8 Adverse effects: 6. Gastrointestinal.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.9

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 9 Adverse effects: 7. Genitourinary.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.10

Comparison 2 CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term), Outcome 10 Adverse effects: 8. Others.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Table 1. Reviews suggested by excluded studies

Medication		Comparison	For people with	Relevant excluded study	Relevant existing Cochrane review
Antiparkinsonian drug ‐ unspecified		Antiparkinsonian treatment versus placebo	Movement disorders	Caffey 1975	‐
Antipsychotic drugs ‐ unspecified	Doses	Any antipsychotic at high chlorpromazine equivalent dosages vs lower chlorpromazine equivalent dosages	Schizophrenia	Lehmann 1983	‐
	Doses	Dose reduction of multiple antipsychotics versus control group		Sukegawa 2008; Sukegawa 2014	‐
	Timing of treatment	Treatment days per week of antipsychotics		Caffey 1975	‐
Chlorpromazine	Mostly versus other antipsychotic drug	Chlorpromazine brand comparisons		Ota 1974	‐
		Chlorpromazine versus clopenthixol		Clark 1970b	Kumar 2005
		Chlorpromazine versus clozapine		Chen 2002	Essali 2009; Saha 2016
		Chlorpromazine versus haloperidol		Eitan 1992	Leucht 2008; Tardy 2014
		Chlorpromazine versus placebo		Borison 1991; Clark 1967; Clark 1970a; Clark 1970b; Eitan 1992	Adams 2014
		Chlorpromazine versus rimcazole		Borison 1991	‐
		Chlorpromazine versus risperidone		Chen 2002	Hunter 2003; Saha 2016
		Chlorpromazine versus thioridazine		Altman 1973; Eitan 1992	Fenton 2007
		Chlorpromazine versus trifluoperazine		Eitan 1992	de Oliveira Marques 2004; Tardy 2014a
	Doses	Ultra‐low doses of chlorpromazine		Altman 1973; Andrews 1976; Gibbs 1956; Yuan‐Guang 1994	‐
	Doses	Ultra‐low doses of thioridazine		Altman 1973	‐
	Timing of treatment	Night doses versus daytime doses of chlorpromazine		Altman 1973; Kalyanasundaram 1981	‐
		Single doses versus divided doses of chlorpromazine		Altman 1973; Kalyanasundaram 1981	‐
		Q.I.D versus O.D of chlorpromazine		Jeste 1977	‐
Clopenthixol		Clopenthixol versus placebo		Clark 1970b	Kumar 2005
Clozapine		Clozapine versus risperidone		Chen 2002	Komossa 2011; Tuunainen 2000
Dextroamphetamine		Dextroamphetamine versus imipramine		Casey 1961	Rummel‐Kluge 2006
		Dextroamphetamine versus isocarboxazid			Rummel‐Kluge 2006
		Dextroamphetamine versus placebo			‐
		Dextroamphetamine versus trifluoperazine			‐
Haloperidol		Haloperidol versus placebo		Eitan 1992	Adams 2013
		Haloperidol versus trifluoperazine			de Oliveira Marques 2004; Dold 2015
		Haloperidol versus thioridazine			Fenton 2007; Tardy 2014
Imipramine		‐		Casey 1961	‐
Isocarboxazid		Isocarboxazid versus placebo		Casey 1961	Rummel‐Kluge 2006
Isocarboxazid		Isocarboxazid versus trifluoperazine		Casey 1961	Rummel‐Kluge 2006
Rimcazole		Rimcazole versus placebo		Borison 1991	‐
Rimcazole	Doses	Rimcazole dose		Borison 1991	‐
Risperidone		‐		Chen 2002	‐
Thioridazine		Thioridazine versus placebo		Eitan 1992	Fenton 2007
	Timing of treatment	Night doses versus daytime doses of thioridazine		Altman 1973	‐
	Timing of treatment	Thioridazine ‐ single doses versus divided doses		Altman 1973	‐
Trifluoperazine		Trifluoperazine versus placebo		Casey 1961; Eitan 1992	Koch 2014
		Trifluoperazine versus placebo		Casey 1961; Eitan 1992
		Trifluoperazine versus thioridazine		Eitan 1992	de Oliveira Marques 2004; Fenton 2007; Tardy 2014a
Trihexyphenidyl		Trihexyphenidyl versus placebo	Movement disorders	Yuan‐Guang 1994	‐
Vitamin preparation		Vitamin preparation versus placebo	Schizophrenia	Joshi 1982	Magalhaes 2016

Table 1. Reviews suggested by excluded studies

Ir a la tabla de la revisión

Table 2. Suggested design for trial

Methods	Allocation: clearly randomised, well‐described concealment. Blindness: triple‐blinding clearly described including information on method administration, volume and concentration of chlorpromazine. Duration: 28 weeks (2 weeks of no antipsychotic medication).
Participants	Diagnosis: people with schizophrenia ‐ diagnosed by any criteria. Age: any. Sex: both. N = 450.* History: acute or long‐term illness. Excluded: borderline cases, mental deficiency (IQ < 70), bad physical health with complicating organic illness or known brain damage, medical conditions constraining use of high doses, alcoholism or drug use, showing severe suicidal or aggressive impulses.
Interventions	1. Chlorpromazine: dose 300 mg/day. N = 150. 2. Chlorpromazine: dose 600 mg/day. N = 150. 3. Chlorpromazine: dose 900 mg/day. N = 150.
Outcomes	Leaving the study early (reasons, timing, gender and treatment group provided). Deaths. Adverse effects (clinically important and specific). Needing additional medication (information about doses, timings and reasons for drug administration provided). Effectiveness: Total number improved/not improved global state. Total number improved/not improved mental state. Total number improved/not improved behavioural state. Total number with improved quality of life. Total number satisfied with treatment. Total number with improved social skills. Total number with improved life skills
Notes	* 150 in each group allows for good statistical power.

Table 2. Suggested design for trial

Ir a la tabla de la revisión

Summary of findings for the main comparison. CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to MEDIUM DOSE (401 mg/day to 800 mg/day) for people with schizophrenia

CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to MEDIUM DOSE (401 mg/day to 800 mg/day) for people with schizophrenia
Patient or population: people with schizophrenia Settings: hospital Intervention: CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) Comparison: MEDIUM DOSE (401 mg/day to 800 mg/day)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	MEDIUM DOSE (401‐800 mg/day)	CHLORPROMAZINE LOW DOSE (≤ 400 mg/day)
Global state: no improvement ‐ short term	Low¹		RR 0.83 (0.28 to 2.44)	60 (1 study)	⊕⊝⊝⊝ very low^1,2,4
	100 per 1000	83 per 1000 (28 to 244)
	Moderate¹
	200 per 1000	166 per 1000 (56 to 488)
	High¹
	300 per 1000	249 per 1000 (84 to 732)
Global state: needing additional medication (sedation with chloral hydrate or a barbiturate > 5 times) ‐ medium term	Low¹		RR 3.09 (0.4 to 23.64)	50 (1 study)	⊕⊕⊝⊝ low^3,4,
	20 per 1000	62 per 1000 (8 to 473)
	Moderate¹
	60 per 1000	185 per 1000 (24 to 1000)
	High¹
	100 per 1000	309 per 1000 (40 to 1000)
Mental state: average endpoint score (PANSS total, high=poor)		The mean mental state: average endpoint score (PANSS total, high = poor) in the intervention groups was 0.36 higher (5.39 lower to 6.11 higher)		60 (1 study)	⊕⊝⊝⊝ very low^2,4,5
Leaving the study early ‐ any reason	Low¹		RR 1.06 (0.32 to 3.55)	70 (2 studies)	⊕⊕⊕⊝ moderate⁶
	50 per 1000	53 per 1000 (16 to 177)
	Moderate¹
	100 per 1000	106 per 1000 (32 to 355)
	High¹
	150 per 1000	159 per 1000 (48 to 532)
Behaviour: agitation and restlessness ‐ medium term (categorised as adverse event)	Study population		RR 1.59 (0.07 to 37.03)	50 (1 study)	⊕⊝⊝⊝ very low^3,4,7
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	0 per 1000	0 per 1000 (0 to 0)
Adverse effects: extrapyramidal symptoms (unspecified extrapyramidal symptoms ‐ short term)	Low		RR 0.47 (0.30 to 0.74)	108 (2 studies)	⊕⊕⊕⊝ moderate⁸
	200 per 1000	94 per 1000 (60 to 148)
	Moderate
	500 per 1000	235 per 1000 (150 to 370)
	High
	800 per 1000	376 per 1000 (240 to 592)
Adverse event: death	No trial reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Indirectness: rated serious: downgraded by 1 ‐ unclear if clinically important improvement, no prespecified medium‐term data available. ² Risk of bias: rated 'serious': downgraded by 1 ‐ randomisation not described well, no mention of allocation concealment or blinding. ³ Risk of bias: rated 'serious': downgraded by 1 ‐ randomisation not described well, no mention of allocation concealment, unclear regarding selection bias or management of lost data, industry partnering of author. ⁴ Imprecision: rated 'serious': downgraded by 1 ‐ only one study providing data, there are very few participants, number of events small. ⁵ Indirectness: rated 'serious': downgraded by 1 ‐ no data available for prespecified outcome of 'no clinically important change in general mental state' ‐ only scale scores reported. ⁶ Risk of bias: rated 'serious' : downgraded by 1 ‐ randomisation not described well, no mention of allocation concealment, unclear if loss to follow‐up data for Chouinard 1976 accurate as we have made assumptions it is zero in these groups. ⁷ Indirectness: rated 'serious' : downgraded by 1 ‐ no data available for prespecified outcome of no clinically important change in general behaviour ‐ behaviour of agitation/restlessness rated within trial as adverse event. ⁸ Risk of bias: rated 'serious' : downgraded by 1 ‐ randomisation not described well, no mention of allocation concealment, Xu 2009 not blinded, concern regarding selective reporting (Wode‐Helgodt 1978 ).

Summary of findings for the main comparison. CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to MEDIUM DOSE (401 mg/day to 800 mg/day) for people with schizophrenia

Ir a la tabla de la revisión

Summary of findings 2. CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to HIGH DOSE (> 800 mg/day ‐ all medium term) for people with schizophrenia

CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to HIGH DOSE (> 800 mg/day‐ all medium term) for people with schizophrenia
Patient or population: patients with people with schizophrenia Settings: Intervention: CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) Comparison: HIGH DOSE (> 800 mg/day ‐ all medium term)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comment
	Assumed risk	Corresponding risk
	HIGH DOSE (>800 mg/day‐ all medium term)	CHLORPROMAZINE LOW DOSE (≤ 400 mg/day)
Global state: no clinically important improvement ‐ medium term	Low¹		RR 1.13 (1.01 to 1.25)	416 (1 study)	⊕⊕⊕⊝ moderate¹
	300 per 1000	339 per 1000 (303 to 375)
	Moderate¹
	700 per 1000	791 per 1000 (707 to 875)
	High¹
	900 per 1000	1000 per 1000 (909 to 1000)
Global state: requiring additional medication (sedation with chloral hydrate or a barbiturate > 5 times)	See comment	See comment	Not estimable	0 (0)	See comment	No data available
Mental state: no clinically important change in mental state	See comment	See comment	Not estimable	0 (0)	See comment	No data available
Leaving the study early ‐ any reason	Low¹		RR 0.60 (0.40 to 0.89)	416 (1 study)	⊕⊕⊕⊝ moderate¹
	100 per 1000	60 per 1000 (40 to 89)
	Moderate¹
	250 per 1000	150 per 1000 (100 to 222)
	High¹
	500 per 1000	300 per 1000 (200 to 445)
Behaviour: deterioration of behaviour (categorised as reason to leave early)	Low		RR 2.70 (1.34 to 5.44)	416 (1 study)	⊕⊕⊝⊝ low¹,²
	20 per 1000	54 per 1000 (27 to 109)
	Moderate
	50 per 1000	135 per 1000 (67 to 272)
	High
	100 per 1000	270 per 1000 (134 to 544)
Adverse effects: unspecified extrapyramidal symptoms	Low		RR 0.43 (0.32 to 0.59)	416 (1 study)	⊕⊕⊕⊝ moderate¹
	200 per 1000	86 per 1000 (64 to 118)
	Moderate
	500 per 1000	215 per 1000 (160 to 295)
	High
	700 per 1000	301 per 1000 (224 to 413)
Adverse event: death	Low		RR 0.33 (0.01 to 8.14)	416 (1 study)	⊕⊕⊕⊝ moderate¹
	0 per 1000	0 per 1000 (0 to 0)
	Moderate
	5 per 1000	2 per 1000 (0 to 41)
	High
	50 per 1000	17 per 1000 (0 to 407)
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Risk of bias: rated serious: downgraded by 1 ‐ randomisation not described well, no mention of allocation concealment, concern regarding selective reporting. ²Indirectness: rated serious: downgraded by 1 ‐ unclear if clinically important change in behaviour, rated within trial as leaving the study early outcome.

Summary of findings 2. CHLORPROMAZINE LOW DOSE (≤ 400 mg/day) compared to HIGH DOSE (> 800 mg/day ‐ all medium term) for people with schizophrenia

Ir a la tabla de la revisión

Comparison 1. CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1. Not improved ‐ short term (CGI‐SI) Show forest plot	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.28, 2.44]

2 Global state: 2. Requiring additional medication (sedation with chloral hydrate or a barbiturate > 5 times) ‐ medium term Show forest plot	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	3.09 [0.40, 23.64]

3 Leaving the study early Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 any reason	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.32, 3.55]
3.2 adverse effects	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.02, 2.32]
3.3 inefficacy of treatment	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	4.24 [0.24, 74.01]
3.4 other reason	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.09, 9.27]
4 Mental state: 1a. Average endpoint score (BPRS total, high = poor) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 anxious depression	1	22	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.35, 0.15]
4.2 thinking disturbance	1	22	Mean Difference (IV, Fixed, 95% CI)	2.60 [‐0.24, 5.44]
4.3 withdrawal retardation	1	22	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐3.76, ‐0.24]
5 Mental state: 1b. Average endpoint score (PANSS total and subscores, high = poor) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 negative	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐2.34, 2.00]
5.2 positive	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.24 [‐1.98, 1.50]
5.3 total	1	60	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐5.39, 6.11]
6 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 akathisia ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.28, 6.68]
6.2 akinesia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
6.3 dystonia ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.05, 1.29]
6.4 gait disturbance ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.36 [0.11, 1.17]
6.5 muscle tension ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.03, 0.67]
6.6 rigidity ‐ elbow ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.21, 1.31]
6.7 rigidity ‐ unspecified ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 14.05]
6.8 tremor ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.17, 1.10]
6.9 unspecified extrapyramidal symptoms ‐ short term	2	108	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.30, 0.74]
6.10 unspecified extrapyramidal symptoms ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.26 [0.05, 1.27]
7 Adverse effects: 2. Anticholinergic Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 blurred vision ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.30 [0.06, 1.63]
7.2 ejaculation disturbance ‐ short term	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.3 erectile disturbance ‐ short term	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7.4 constipation ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [0.42, 7.99]
7.5 constipation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
7.6 salivation ‐ dry mouth ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.58, 2.34]
7.7 salivation ‐ too much ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.00, 1.85]
7.8 tachycardia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
7.9 urinary disturbance/trouble starting urination ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.37, 24.58]
8 Adverse effects: 3. Cardiovascular Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 electrocardiogram abnormal ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.05, 0.94]
8.2 orthostatic symptoms (faint, dizzy, weak) ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	2.0 [0.21, 18.98]
8.3 orthostatic symptoms ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
8.4 tachycardia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.05, 4.75]
8.5 vertigo ‐ short term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.21, 5.07]
9 Adverse effects: 4. Central nervous system ‐ other than extrapyramidal symptoms Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 depression ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 drowsiness ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.47, 2.14]
9.3 EEG abnormal ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.78 [0.33, 1.82]
9.4 head feels heavy ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.15 [0.02, 1.34]
9.5 headache ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	2.35 [0.12, 46.22]
9.6 sedation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.05, 0.55]
9.7 somnolence ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.59, 2.08]
9.8 vertigo ‐ short term	1	48	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.19, 4.43]
10 Adverse effects: 5. Dermatological Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 dermatitis ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
10.2 rash ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.39, 4.62]
10.3 rash ‐ 'photosensitivity: erythema' ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.03, 7.74]
11 Adverse effects: 6. Endocrine and metabolic Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 amenorrhoea ‐ short term	1	28	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.03, 6.74]
11.2 lactation ‐ short term	1	28	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.01, 3.73]
11.3 metrorrhagia ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.01, 4.11]
12 Adverse effects: 7. Gastrointestinal Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

12.1 constipation ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	1.82 [0.42, 7.99]
12.2 constipation ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 2.09]
12.3 unspecified ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.27, 93.55]
13 Adverse effects: 8. Genitourinary Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

13.1 urinary disturbance/trouble starting urination ‐ short term	2	70	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.37, 24.58]
14 Adverse effects: 9. Haematological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

14.1 agranulocytosis ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
14.2 anaemia ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
15 Adverse effects: 10. Hepatological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

15.1 abnormal liver function ‐ short term	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.33, 5.45]
16 Adverse effects: 11. Others Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

16.1 agitation and restlessness ‐ medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.07, 37.03]
16.2 excitement ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 14.05]
16.3 restlessness, insomnia ‐ short term	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.22, 2.60]

Comparison 1. CHLORPROMAZINE LOW DOSE (≤400 mg/day) vs MEDIUM DOSE (401‐800 mg/day)

Ir a la tabla de la revisión

Comparison 2. CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: Not improved, severely ill, relapse (GAS) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 no clinically important improvement	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [1.01, 1.25]
1.2 severely ill	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.96, 1.24]
1.3 relapse	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	2.25 [1.17, 4.32]
2 Leaving the study early Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 any reason	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.40, 0.89]
2.2 adverse effects	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.03, 0.26]
2.3 death	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 8.14]
2.4 deterioration of behaviour	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	2.7 [1.34, 5.44]
3 Adverse effects: 1. Central nervous system ‐ extrapyramidal symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 akathisia	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.55, 1.83]
3.2 dystonia	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.02, 0.45]
3.3 parkinsonian reaction	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.52 [0.30, 0.90]
3.4 required antiparkinsonian medication	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.26, 0.59]
3.5 unspecified	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.32, 0.59]
4 Adverse effects: 2. Anticholinergic symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 blurred vision	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.14]
4.2 constipation	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.09, 0.79]
4.3 salivation ‐ too little (dry mouth)	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.21 [0.07, 0.61]
4.4 salivation ‐ too much	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.04, 0.90]
4.5 urinary disturbance	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
5 Adverse effects: 3. Central nervous system ‐ other than extrapyramidal symptoms Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 drowsiness	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.27, 0.57]
5.2 seizures	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.04, 0.74]
6 Adverse effects: 4. Cardiovascular Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 dizziness, faintness	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.3 [0.16, 0.56]
6.2 peripheral oedema	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.07, 1.63]
6.3 syncope	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
7 Adverse effects: 5. Dermatological Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 photosensitivity	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.03, 0.24]
7.2 rashes, itching	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.13 [0.03, 0.58]
8 Adverse effects: 6. Gastrointestinal Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 constipation	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.27 [0.09, 0.79]
8.2 diarrhoea	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
8.3 nausea, vomiting	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.19, 2.33]
9 Adverse effects: 7. Genitourinary Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 urinary disturbance	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.5 [0.09, 2.70]
10 Adverse effects: 8. Others Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 occular ‐ any lens/corneal opacities	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.23, 0.52]
10.2 occular ‐ corneal changes only	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.07 [0.02, 0.30]
10.3 occular ‐ lens changes only	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.75 [0.88, 3.46]
10.4 occular ‐ lens and corneal changes	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	0.06 [0.02, 0.26]
10.5 nasal congestion	1	416	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.14, 7.03]

Comparison 2. CHLORPROMAZINE LOW DOSE (≤400mg/day) vs HIGH DOSE (>800 mg/day ‐ all medium term)

Ir a la tabla de la revisión

	Idioma de la Revisión Cochrane Escoja su idioma de preferencia para las revisiones Cochrane y otros contenidos. Las secciones sin una traducción aparecerán en inglés.

	Idioma de la web Escoja su idioma de preferencia para la web de la Biblioteca Cochrane.

Idioma de la Revisión Cochrane

Idioma de la web

Referencias

منابع مطالعات واردشده در این مرور

Chouinard 1976 {published data only}

Clark 1972 {published data only}

Prien 1968 {published data only}

Wode‐Helgodt 1978 {published data only}

Xu 2009 {published data only}

منابع مطالعات خارج‌شده از این مرور

Altman 1973 {published data only}

Andrews 1976 {published data only}

Bartko 1988 {published data only}

Borison 1991 {published data only}

Caffey 1975 {published data only}

Casey 1961 {published data only}

Chen 2002 {published data only}

Clark 1960 {published data only}

Clark 1961 {published data only}

Clark 1967 {published data only}

Clark 1970a {published data only}

Clark 1970b {published data only}

Clark 1978 {published data only}

Cooper 1973 {published data only}

Crane 1968 {published data only}

Curry 1976 {published data only}

Danion 1992 {published data only}

Eitan 1992 {published data only}

Gibbs 1956 {published data only}

Green 1996 {published data only}

Hartley 1978 {published data only}

Janakiramaiah 1982 {published data only}

Jeste 1977 {published data only}

Joshi 1982 {published data only}

Kalyanasundaram 1981 {published data only}

Lehmann 1983 {published data only}

Ota 1974 {published data only}

Pigache 1993 {published data only}

Schiele 1959 {published data only}

Sukegawa 2008 {published data only}

Sukegawa 2012 {published data only}

Sukegawa 2014 {published data only}

Yuan‐Guang 1994 {published data only}

منابع اضافی

Adams 2013

Adams 2014

Altman 1996

Armitage 1971

Barbato 1998

Bazire 2014

Bland 1997

BNF 2014

Boissel 1999

Bollini 1994

Carpenter 1994

Clark 1970

Davis 1974

de Oliveira Marques 2004

Deeks 2000

Deeks 2011

Divine 1992

Dold 2015

Donner 2002

Egger 1997

Elbourne 2002

Endicott 1976

Essali 2009

Fenton 2007

Furukawa 2006

Geddes 2000

Gulliford 1999

Guy 1976

Higgins 2003

Higgins 2008

Higgins 2011

Higgins 2011a

Hunter 2003

Hutton 2009

Jüni 2001

Kay 1986