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Benzodiazepines for psychosis‐induced aggression or agitation

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Referencias

References to studies included in this review

Ir a:

Barbee 1992 {published data only}

Barbee JG, Mancuso DM, Freed CR, Todorov AA. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia [published erratum appears in Am J Psychiatry 1992 Aug;149(8):1129] [see comments]. American Journal of Psychiatry 1992;149:506‐10.

Battaglia 1997 {published data only}

Battaglia J, Moss S, Rush J, Kang J, Mendoza R, Leedom L. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double‐blind, emergency department study. American Journal of Emergency Medicine 1997;15:335‐40.

Bienek 1998 {published data only}

Bieniek SA, Ownby RL, Penalver A, Dominguez RA. A double‐blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy 1998;18:57‐62.

Chouinard 1993 {published data only}

Chouinard G, Annable L, Turnier L, Holobow N, Szkrumelak N. A double‐blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms [see comments]. Canadian Journal of Psychiatry 1993;38:S114‐S121.

Dorevitch 1999 {published data only}

Dorevitch A, Katz N, Zemishlany Z, Aizenberg D, Weizman A. Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. American Journal of Psychiatry 1999;156:142‐4.

Foster 1997 {published data only}

Foster S, Kessel J, Berman ME, Simpson GM. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. International Clinical Psychopharmacology 1997;12:175‐9.

Lerner 1979 {published data only}

Lerner Y, Lwow E, Levitin A, Belmaker RH. Acute high‐dose parenteral haloperidol treatment of psychosis. American Journal of Psychiatry 1979;136:1061‐4.

Meehan 2001 {published data only}

Meehan KZ. A double‐blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. Journal of Clinical Psychopharmacology 2001;21:389‐97.

Salzman 1991 {published data only}

Salzman C, Solomon D, Miyawaki E, Glassman R. Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior. Journal of Clinical Psychiatry 1991;52(4):177‐80.

Solomon 1990 {published data only}

Solomon DA, Miyawaki E, Salzman C. Benzodiazepine augmentation of the treatment of disruptive psychotic behavior. [Review] [46 refs]. Progress in Drug Research 1990;35:139‐49.

Subramaney 1998 {published data only}

Subramaney U, Brook S, Berk M. A prospective randomised double‐blind controlled study of the efficacy of lorazepam versus clothiapine in the control of acutely behaviourally disturbed patients. South African Medical Journal 1998;88:307‐10.

References to studies excluded from this review

Ir a:

Arana 1986 {published data only}

Arana GW, Ornsteen ML, Kanter F, Friedman HL, Greenblatt DJ, Shader RI. The use of benzodiazepines for psychotic disorders: a literature review and preliminary clinical findings. Psychopharmacology Bulletin 1986;22:77‐87.

Garza‐Trevino 1989 {published data only}

Garza‐Trevino ES, Hollister LE, Overall JE, Alexander WF. Efficacy of combinations of intramuscular antipsychotics and sedative‐hypnotics for control of psychotic agitation [see comments]. American Journal of Psychiatry 1989;146:1598‐601.

Lenox 1992 {published data only}

Lenox RH, Newhouse PA, Creelman WL, Whitaker TM. Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double‐blind study. Journal of Clinical Psychiatry 1992;53:47‐52.

Nestoros 1982 {published data only}

Nestoros JN. Diazepam in high doses is effective in schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 1982;6:513‐6.

TREC 2003 {published data only}

TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003;327(27 (September)):1‐6.

TREC 2004 {published data only}

Alexander J, Tharyan P, Adams CE, John T, Mol C, Philip J. Rapid tranquilisation of violent or agitated patients in a psychiatric emergancy setting: a pragmatic randomised trial of intramuscular lorazepam versus haloperidol plus promethazine. British Journal of Psychiatry 2004;185:63‐9.

Veser 2002 {published data only}

Veser F, Zealburg J, Veser B, Zhu Y, Gharabawi G. Oral risperidone in the management of agitated behavior in emergency settings. Journal of the European College of Neuropsychopharmacology 2002;12(Suppl 3):S313.

Wyant 1990 {published data only}

Wyant M, Diamond BI, O'Neal E, Sloan A. The use of midazolam in acutely agitated psychiatric patients. Psychopharmacology Bulletin, 29th Annual Meeting of the New Clinical Drug Evaluation Unit. 1990; Vol. 26:126‐9.

Yang 2003 {published data only}

Yang X, Wang Z, Ling Z. A randomly controlled comparison of risperidone added with intramuscular clonazepam in the treatment of excitement of schizophrenia. Shanghai Archives of Psychiatry 2003;15(2):98‐9.

Additional references

Ir a:

Alderson 2004

Alderson P, Green S, Higgins JPT. Cochrane Reviewers' Handbook 4.2.2 [updated December 2003]. Cochrane Database of Systematic Reviews 2004, Issue 1. [In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd]

Altman 1996

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

Battaglia 1997

Battaglia J, Moss S, Rush J, Kang J, Mendoza R, Leedom L. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double‐blind, emergency department study. American Journal of Emergency Medicine 1997;15(4):335‐40.

Binder 1999

Binder RL, McNiel DE. Emergency psychiatry: contemporary practices in managing acutely violent patients in 20 psychiatric emergency rooms. Psychiatric Services 1999;50(12):1553‐4.

Bland 1997

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

Csernansky 1988

Csernansky JG, Riney SJ, Lombrozo L, Overall JE, Hollister LE. Double‐blind comparison of alprazolam, diazepam, and placebo for the treatment of negative schizophrenic symptoms. Archives of General Psychiatry 1988;45(7):655‐9.

Cunnane 1994

Cunnane JG. Drug management of disturbed behaviour by psychiatrists. Psychiatric Bulletin 1994;18:138‐9.

Cure 2001

Cure S, Carpenter S. Droperidol for acute psychosis. Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/14651858.CD002830]

Divine 1992

Divine GW, Brown JT, Frazier LM. The unit of analysis error in studies about physicians' patient care behavior. Journal of General Internal Medicine 1992;7(6):623‐9.

Donner 2002

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

Dubin 1988

Dubin WR. Rapid tranquilization: antipsychotics or benzodiazepines?. Journal of Clinical Psychiatry 1988;49(Supplement):5‐12.

Egger 1997

Egger M, Smith GD, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315:629‐34.

Extein 1980

Extein I. Psychopharmacology in psychiatric emergencies. International Journal of Psychiatry in Medicine 1980;10(3):189‐204.

Fava 1997

Fava M. Psychopharmacologic treatment of pathologic aggression. Psychiatric Clinics of North America 1997;20(2):427‐51.

Gulliford 1999

Gulliford MC. 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 1970

Guy W, Bonato RR, eds. Clinical Global Impressions. In: Manual for the ECDEU Assessment Battery 2. Rev ed. National Institute of Mental Health, 1970.

Huf 2000

Huf G, Countino E, Adams CE. A survey of rapid tranquillisation in psychiatric emergency rooms of Rio de Janeiro. manuscript in preparation2000.

Joy 2001

Joy CB, Adams CE, Lawrie SM. Haloperidol versus placebo for schizophrenia. Cochrane Database of Systematic reviews 2001, Issue 2. [DOI: 10.1002/14651858.CD003082.pub2]

Kay 1987

Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 1987;13:261‐76.

Levy 1996

Levy RH. Sedation in acute and chronic agitation. Pharmacotherapy 1996;16(6 pt 2):152S‐9S; 166S‐168S.

Lorr 1963

Lorr M, Klett CJ, McNair DM, Lasky JJ. Inpatient Multidimensional Psychiatric Scale. Palo Alto: Consulting Psychologists Press, 1963.

Marshall 2000

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.

Mendelson 1992

Mendelson WB. Clinical distinctions between long‐acting and short‐acting benzodiazepines. Journal of Clinical Psychiatry 1992;53(Supplement):4‐7; discussion 8‐9.

Moher 2001

Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallel‐group randomized trials. JAMA 2001;285:1987‐91.

Overall 1962

Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962;10:799‐812.

Pilowsky 1992

Pilowsky LS, Ring H, Shine PJ, Battersby M, Lader M. Rapid tranquillisation. A survey of emergency prescribing in a general psychiatric hospital. British Journal of Psychiatry 1992;160:831‐5.

Stimmel 1996

Stimmel GL. Benzodiazepines in schizophrenia. Pharmacotherapy 1996;16(6 pt 2):148S‐51S; 166S‐8S.

TREC 2004

Alexander J, Tharyan P, Adams CE, John T, Mol C, Philip J. Rapid tranquilisation of violent or agitated patients in a psychiatric emergancy setting: a pragmatic randomised trial of intramuscular lorazepam versus haloperidol plus promethazine. British Journal of Psychiatry 2004;185:63‐9.

Ukoumunne 1999

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

Wolkowitz 1986

Wolkowitz OM, Pickar D, Doran AR, Breier A, Tarell J, Paul SM. Combination alprazolam‐neuroleptic treatment of the positive and negative symptoms of schizophrenia. American Journal of Psychiatry 1986;143(1):85‐7.

Wolkowitz 1989

Wolkowitz OM, Breier A, Doran A, Lucas P, Kelsoe J, Paul SM. Alprazolam augmentation of neuroleptics in schizophrenia. American Journal of Psychiatry 1989;146(8):1087‐8.

Wolkowitz 1991

Wolkowitz OM, Pickar D. Benzodiazepines in the treatment of schizophrenia: a review and reappraisal. American Journal of Psychiatry 1991;148(6):714‐26.

Yudofsky 1986

Yudofsky SC, Silver JM, Jackson W, Endicott J, Williams D. The Overt Aggression Scale for the Objective Rating of Verbal and Physical Aggression. American Journal of Psychiatry 1986;143(1):35‐9.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Barbee 1992

Methods

Allocation: randomised.
Blindness: double.
Duration: 72 hours.
Design: antipsychotic versus combined benzodiazepine/antipsychotic.

Participants

Diagnosis: schizophrenia (DSM‐III R).
N=28.
Age: mean 33 years.
Sex: 12 M; 16 F.
History: gave informed consent.
Setting: psychiatric emergency service, US hospital.

Interventions

1. Alprazolam + haloperidol: dose alprazolam 1mg/oral, haloperidol 5 mg/oral. N=14.

2. Haloperidol + placebo: dose 5 mg/bid. N=14.

Repeat dose given within first 24 hours if psychotic subscale was>11. Total dose administered on day 1 repeated days 2 and 3. Each patient received a minimum of 2 doses.

Mean number of doses: haloperidol 2.1, combination 3.2.

Outcomes

Leaving the study early.
Mental state: BPRS, BPRS‐psychosis subscale.
Adverse events: EPS, anticholinergic medication.
Hospital & service: Early discharge.

Unable to use ‐
Mental state: SANS, SAPS (no usable data).

Notes

ITT: not stated.
Follow‐up: 70%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Battaglia 1997

Methods

Allocation: randomised ‐ computer generated random numbers.
Blindness: double.
Duration: 24 hours.
Design: randomised trial of benzodiazepine versus antipsychotic versus combined benzodiazepine/antipsychotic.

Participants

Diagnosis: psychosis and uncontrolled behaviour (agitated, aggressive, destructive, assault or restless behaviour).
N=98.
Age: mean 34 years.
Sex: 73 M; 25 F.
History: informed consent wherever possible.
Setting: ED, US hospital.

Interventions

1. Lorazepam + haloperidol: dose lorazepam 2 mg/IM, haloperidol 5 mg/IM/max. 6 doses. N=32.

2. Lorazepam: dose 2 mg/IM/max. 6 doses. N=31.

3. Haloperidol: dose 5 mg/IM/max. 6 doses. N=35.

Administered during first 12 hrs of study. First three injections at least 1 hr apart and remainder 2 hrs apart. Total not to exceed 6 doses. Need for subsequent doses made by blinded evaluator. Most patients had < 3 doses (lorazepam: 74%; haloperidol: 71%; combination: 91%).

Outcomes

Global impression: Additional medication.
Mental state: BPRS‐psychosis subscale.
Adverse events: EPS, side‐effects.

Unable to use ‐
Behaviour: ABS.
Mental state: BPRS‐anxiety subscale (unvalidated subscores).
Global impression: CGI (no usable data).

Notes

ITT: not stated.
Follow‐up: not clear.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Bienek 1998

Methods

Allocation: randomised.
Blindness: double.
Duration: 48 hours, 7 days in total.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: acutely agitated behaviour.
N=20.
Age: mean 41 years.
Sex: 13 M; 7 F.
History: informed consent waived.
Setting: psychiatric emergency service, US hospital.

Interventions

1. Lorazepam + haloperidol: dose lorazepam 2 mg/IM, haloperidol 5 mg/IM. N=9.

2. Lorazepam: dose 2 mg/IM. N=11.

Repeated once at 60 min if patients were still severely agitated.

Outcomes

Leaving the study early.
Global impression: Additional medication, CGI.
Behaviour: OAS.
Adverse events: EPS.

Notes

ITT: not applicable.
Follow‐up: 100%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Chouinard 1993

Methods

Allocation: randomised.
Blindness: double.
Duration: 2 hours.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: bipolar affective illness, manic phase schizoaffective disorder, schizophreniform disorder, brief reactive disorder or atypical psychosis, (DSM‐III).
N=16.
Age: range 18‐60 years.
Sex: 10 M; 6 F.
History: informed consent given.
Setting: ED, hospital, Canada.

Interventions

1. Clonazepam: dose 1‐2 mg/IM. N=8.

2. Haloperidol: dose 5‐10 mg/IM. N=8.

Given at 0, 0.5 and 1 hour; mean dose clonazepam (5.4 mg), haloperidol (19.4 mg).

Dosage adjusted by blinded psychiatrist; procyclidine given to haloperidol group and procyclidine placebo given to clonazepam group. Both groups still received medications as usual.

Outcomes

Leaving the study early.
Global impression: Sedation, CGI.
Mental state: IMPS.
Adverse events: EPS.

Unable to use ‐
Behaviour: TMBS (no usable data).
Mental state: NOSIE‐subscore (unvalidated subscale data).

Notes

ITT: not stated.
Follow‐up: 88%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Dorevitch 1999

Methods

Allocation: randomised, table of random numbers.
Blindness: double, not clear whether dose adjustment was blinded.
Duration: 2 hours.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: schizophrenia (N=19), schizoaffective disorder (N=7), bipolar (N=2) (DSM IV, axis 1 SCID).
N=28.
Age: range 20‐60 years.
Sex: 13 M; 15 F.
History: did not need consent.
Setting: psychiatric hospital, Israel.

Interventions

1. Flunitrazepam: dose 1 mg/IM/single dose. N=15.

2. Haloperidol: dose 5 mg/IM/single dose. N=13.

Patients were monitored for 120 minutes. Subjects on routine psychotropic treatment.

Outcomes

Leaving the study early.
Global impression: Sedation.
Behaviour: OAS.
Adverse events: EPS.

Notes

ITT: not stated.
Follow‐up: 100%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Foster 1997

Methods

Allocation: randomised.
Blindness: double, unclear whether the decision to give additional doses was blinded.
Duration: 4 hours.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: schizophrenia (N=13), bipolar (N=13), schizoaffective (N=4), psychotic disorder not otherwise specified (N=7).
N=37.
Age: range 18‐61 years.
Sex: 26 M; F 11.
History: judged by emergency room staff to be an imminent danger to themselves and required 4‐point restraint.
Setting: psychiatric emergency service, US hospital.

Interventions

1. Lorazepam: dose 2 mg/oral or IM/every 30 minutes for 4h. N=17.

2. Haloperidol: dose 5 mg/oral or IM/every 30 minutes for 4h. N=20.

Medication was administered every 30 min for 4h until the patient was sedated or no longer posed a danger to themselves or staff.

Outcomes

Global impression: Sedation, CGI.
Mental state: BPRS.
Adverse events: EPS.

Notes

ITT: not stated.
Follow‐up: not clear.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Lerner 1979

Methods

Allocation: randomised*.
Blindness: observer‐blinded.
Duration: 24 hours.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: paranoid schizophrenia (N=9), schizoaffective schizophrenia (N=9), schizophrenia subtypes (N=5), paranoid states (N=2), manic (N=5), no diagnosis (N=10).
N=40.
Age: mean 33 years.
Sex: 27 M; 13 F.
History: newly admitted psychotic patients.
Setting: psychiatric hospital, Israel.

Interventions

1. Diazepam: dose mean 5‐15 mg/IM/tds. N=20.

2. Haloperidol: dose 10‐15 mg/IM/tds. N=20.

All free from neuroleptics for 48 hours before the study began.

Outcomes

Global impression: Sedation, CGI.
Mental State: BPRS.

Unable to use ‐
Mental state: BPRS‐agitation and hostility subscore (unvalidated subscale data).

Notes

ITT: not applicable.
Follow‐up: not clear.
*States that it was randomised but also states that there was alternation between meds.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Meehan 2001

Methods

Allocation: randomised.
Blindness: unclear.
Duration: 24 hours.
Design: benzodiazepine versus antipsychotic versus placebo.

Participants

Diagnosis: bipolar disorder (DSM‐IV).
N=201.
Age: mean 40 years.
Sex: 107 M; 94 F.
History: inpatients of at least 18 years.
Setting: hospitals in Romania & US.

Interventions

1. Lorazepam: dose 2‐5 mg/IM. N=51.

2. Olanzapine: dose 10‐25 mg/IM. N=99.

3. Placebo. N=51.

Randomised 2:1:1; patients received 1‐3 doses over 3‐20 hours after the first injection based on clinical judgement of investigator.

Outcomes

Leaving the study early.
Global impression: Additional medication, sedation, CGI‐S.
Mental state: PANSS, PANSS‐EC.
Adverse events: EPS, anticholinergic medication, side‐effects.

Unable to use ‐
Behaviour: ABS, ACES (no usable data).
Mental state: YMRS (no usable data).

Notes

ITT: yes.
Follow‐up: 96%.
Placebo group who received a third injection were excluded at 24h analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Salzman 1991

Methods

Allocation: not stated.
Blindness: raters blinded to treatment.
Duration: 48 hours.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: schizophrenia, bipolar, schizoaffective, psychotic depression.
N=60.
Age: mean 34.2 years.
Sex: not stated.
History: consent not required.
Setting: locked ward, US hospital.

Interventions

1. Lorazepam: dose 2 mg/IM/mean no. of injections 1.13. N=30.

2. Haloperidol: dose 5 mg/IM/mean no. of injections 1.10. N=30.

Not clear when additional doses were given.

Outcomes

Global impression: Sedation.
Adverse events: EPS.

Unable to use ‐
Global impression: CGI (no SD).
Behaviour: OAS (no SD).
Mental state: BPRS (no SD).

Notes

ITT: not stated.
Follow‐up: leaving the study early ‐ not clear; sedation 88%; EPS 67%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Solomon 1990

Methods

Allocation: randomised.
Blindness: double.
Duration: 7 days.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: schizophrenia, schizoaffective disorder or bipolar disorder.
N=60.
Age: not stated.
Sex: not stated.
History: inpatients requiring chemical restraint for control of acute psychotic agitation.
Setting: on a locked ward in a US Mental Health Center.

Interventions

1. Lorazepam: dose 2 mg/IM. N=30.

2. Haloperidol: dose 5 mg/IM. N=28.

Appears to have been given as single dose.

Outcomes

Adverse events: EPS.

Unable to use ‐
Behaviour: OAS (no SD).
Mental state: BPRS (no SD).
Global impression: sedation (no usable data).

Notes

ITT: not stated
Follow‐up: leaving the study early ‐not clear; EPS ‐ unclear, appears to have been 100%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear
Subramaney 1998

Methods

Allocation: randomised.
Blindness: double.
Duration: 7 days.
Design: benzodiazepine versus antipsychotic.

Participants

Diagnosis: psychoactive substance abuse (N=24), schizophrenia (N=16) or bipolar disorder (N=14) (DSM‐III R) no diagnosis (N=6).
N=60.
Age: range 18‐45 years.
Sex: 46 M, 14 F.
History: consent obtained from patient or relative.
Setting: psychiatric hospital, South Africa.

Interventions

1. Clothiapine + *haloperidol: dose clothiapine 40 mg/IM, haloperidol 10 mg/IM. N=30.

2. Lorazepam + *haloperidol: dose lorazepam 4 mg/IM, haloperidol 10 mg/IM. N=30.

Dose repeated 6 hourly "if warranted".

Outcomes

Leaving the study early.
Behaviour: OAS.

Unable to use ‐
Mental state: BPRS (no data within 48 hours).
Adverse events: SAS (no data within 48 hours).

Notes

*haloperidol was given to both groups at a fixed dose and assumptions have been made that the effect of this is 'background noise', and therefore this study has been included under the comparison of 'antipsychotics versus benzodiazepines'.

ITT: not stated.
Follow‐up: 100%.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Diagnostic tools:
DSM ‐ Diagnostic Statistical Manual.
SCID ‐ Structured clinical interview.

Rating Scales:

Behaviour ‐
ABS ‐ Agitated Behavior Scale.
ACES ‐ Agitation‐Calmness Evaluation Scale.
OAS ‐ Overt Agression Scale.
TMBS ‐ Target Manic Behaviour Scale.

Global state ‐
CGI ‐ Clinical Global Impression.
MCGRS ‐ Modified Clinical Global Rating Scale.

Mental state ‐
BPRS ‐ Brief Psychiatric Rating Scale.
IMPS ‐ Inpatient Multidimensional Psychiatric Scale.
MBPRS ‐ Modified Brief Psychiatric Rating Scale.
NOSIE ‐ Nurses' Observation Scale for Inpatient Evaluation.
PANSS ‐ Positive and Negative syndrome Scale.
YMRS ‐ Young Mania Rating.

Side‐Effects ‐
EPS ‐ Extrapyramidal Side Effects.
SAS ‐ Simpson Angus Score.
VAS ‐ Visual Analogue Scale.

ITT ‐ Intention to Treat Analysis.

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Arana 1986

Allocation: unclear.
Participants: people with schizophrenia.
Interventions: lorazepam versus lorazepam and haloperidol.
Outcomes: no usable data.

Garza‐Trevino 1989

Allocation: randomised.
Participants: people with mania, schizophrenia, atypical psychosis, miscellaneous diagnoses.
Interventions: lorazepam versus haloperidol versus lorazepam and haloperidol.
Outcomes: no usable data.

Lenox 1992

Allocation: randomised.
Participants: people with bipolar illness, manic type.
Interventions: lorazepam versus haloperidol.
Outcomes: no usable data.

Nestoros 1982

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: diazepam versus placebo.
Outcomes: no usable data.

TREC 2003

Allocation: randomised.
Participants: people who are aggressive or agitated
Intervention: midazolam IM versus haloperidol IM with promethazine.

TREC 2004

Allocation: randomised.
Participants: people who are aggressive or agitated
Interventions: lorazepam IM versus haloperidol IM and promethazine.

Veser 2002

Allocation: randomised.
Participants: people with acute agitation or psychosis.
Interventions: risperidone and lorazepam versus haloperidol and lorazepam versus placebo and lorazepam.
Outcomes: no usable data.

Wyant 1990

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: midazolam versus haloperidol.
Outcomes: no usable data.

Yang 2003

Allocation: randomised.
Participants: people with schizophrenia.
Interventions: risperidone and clonazepam versus haloperidol versus clozapine.

Data and analyses

Open in table viewer
Comparison 1. BENZODIAZEPINES vs PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.66, 1.40]
Analysis 1.1
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

2 Global impression: 2. Sedation ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

1.67 [0.42, 6.61]
Analysis 1.2
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 2 Global impression: 2. Sedation ‐ medium term.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 2 Global impression: 2. Sedation ‐ medium term.

3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor) Show forest plot

1

76

Mean Difference (IV, Fixed, 95% CI)

0.07 [‐0.46, 0.60]
Analysis 1.3
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor).

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor).

4 Global impression: 4. Leaving the study early ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.15, 2.38]
Analysis 1.4
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 4 Global impression: 4. Leaving the study early ‐ medium term.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 4 Global impression: 4. Leaving the study early ‐ medium term.

5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component) Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.40, 0.97]
Analysis 1.5
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component).

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component).

6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor) Show forest plot

1

99

Mean Difference (IV, Fixed, 95% CI)

‐2.57 [‐6.23, 1.09]
Analysis 1.6
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor).

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor).

7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor) Show forest plot

1

101

Mean Difference (IV, Fixed, 95% CI)

‐1.91 [‐3.83, 0.01]
Analysis 1.7
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor).

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor).

8 Adverse events: 1. Extrapyramidal effects Show forest plot

1

94

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.03, 2.96]
Analysis 1.8
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 8 Adverse events: 1. Extrapyramidal effects.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 8 Adverse events: 1. Extrapyramidal effects.

9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.10]
Analysis 1.9
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

10 Adverse events: 3. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 1.10
Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 10 Adverse events: 3. General.

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 10 Adverse events: 3. General.

10.1 dizziness

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.89, 54.87]

10.2 nausea

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

9.0 [0.50, 162.97]

10.3 vomiting

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.32, 27.89]
Open in table viewer
Comparison 2. BENZODIAZEPINES vs ANTIPSYCHOTICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

2

216

Risk Ratio (M‐H, Random, 95% CI)

1.28 [0.51, 3.22]
Analysis 2.1
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

2 Global impression: 2. Sedation ‐ medium term Show forest plot

6

324

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.48, 1.21]
Analysis 2.2
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Sedation ‐ medium term.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Sedation ‐ medium term.

3 Global impression: 3. Average score (CGI‐S, high = poor) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 2.3
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 3 Global impression: 3. Average score (CGI‐S, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 3 Global impression: 3. Average score (CGI‐S, high = poor).

3.1 Short term

1

16

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐0.58, 1.98]

3.2 Medium term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐0.62 [‐1.36, 0.12]

4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor) Show forest plot

2

189

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.07, 0.47]
Analysis 2.4
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor).

5 Global impression: 5. Average score ‐ medium term (CGI‐S, skewed) Show forest plot

Other data

No numeric data
Analysis 2.5

Study

Intervention

mean

SD

N

Chouinard 1993

Clonazepam

2.60

1.70

8

Chouinard 1993

haloperidol

2.80

0.60

8

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 5 Global impression: 5. Average score ‐ medium term (CGI‐S, skewed).

6 Global impression: 6. Leaving the study early ‐medium term Show forest plot

4

254

Risk Ratio (M‐H, Random, 95% CI)

1.70 [0.11, 27.35]
Analysis 2.6
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 6 Global impression: 6. Leaving the study early ‐medium term.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 6 Global impression: 6. Leaving the study early ‐medium term.

7 Behaviour: 1. Not improved ‐ medium term (OAS) Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

2.6 [0.31, 22.05]
Analysis 2.7
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 7 Behaviour: 1. Not improved ‐ medium term (OAS).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 7 Behaviour: 1. Not improved ‐ medium term (OAS).

8 Behaviour: 2. Average aggression score ‐ medium term (OAS, skewed) Show forest plot

Other data

No numeric data
Analysis 2.8

Study

Intervention

mean

SD

N

Subramaney 1998

Lorazepam

1.83

3.14

30

Subramaney 1998

Clothiapine

1.33

2.78

30

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 8 Behaviour: 2. Average aggression score ‐ medium term (OAS, skewed).

9 Mental state: 1. Not improved ‐ medium term (IMPS) Show forest plot

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.34, 6.70]
Analysis 2.9
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 9 Mental state: 1. Not improved ‐ medium term (IMPS).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 9 Mental state: 1. Not improved ‐ medium term (IMPS).

10 Mental state: 2. Average score (BPRS, high = poor) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only
Analysis 2.10
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 10 Mental state: 2. Average score (BPRS, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 10 Mental state: 2. Average score (BPRS, high = poor).

10.1 Short term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐3.26 [‐10.65, 4.13]

10.2 Medium term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐4.07 [‐10.76, 2.62]

11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor) Show forest plot

1

20

Mean Difference (IV, Fixed, 95% CI)

‐7.60 [‐13.87, ‐1.33]
Analysis 2.11
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor).

12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor) Show forest plot

1

66

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐4.65, 4.05]
Analysis 2.12
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor).

13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component) Show forest plot

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

1.84 [1.06, 3.18]
Analysis 2.13
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component).

14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor) Show forest plot

1

146

Mean Difference (IV, Fixed, 95% CI)

5.64 [2.20, 9.08]
Analysis 2.14
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor).

15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor) Show forest plot

1

149

Mean Difference (IV, Fixed, 95% CI)

2.85 [1.14, 4.56]
Analysis 2.15
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor).

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor).

16 Adverse events: 1. Extrapyramidal effects Show forest plot

7

391

Risk Ratio (M‐H, Fixed, 95% CI)

0.17 [0.06, 0.43]
Analysis 2.16
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 16 Adverse events: 1. Extrapyramidal effects.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 16 Adverse events: 1. Extrapyramidal effects.

17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.03, 1.89]
Analysis 2.17
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

18 Adverse events: 3. General Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 2.18
Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 18 Adverse events: 3. General.

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 18 Adverse events: 3. General.

18.1 ataxia

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

2.26 [0.22, 23.71]

18.2 dizziness

2

216

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [0.63, 3.07]

18.3 dry mouth

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

1.88 [0.49, 7.24]

18.4 nausea

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

7.76 [0.89, 67.67]

18.5 speech disorder

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.11, 2.87]

18.6 vomiting

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

13.46 [0.71, 255.70]
Open in table viewer
Comparison 3. BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.79, 1.32]
Analysis 3.1
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

2 Global impression: 2. Not improved ‐ short term (CGI) Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

1.47 [0.66, 3.25]
Analysis 3.2
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 2 Global impression: 2. Not improved ‐ short term (CGI).

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 2 Global impression: 2. Not improved ‐ short term (CGI).

3 Global impression: 3. Leaving the study early ‐ medium term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Analysis 3.3
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 3 Global impression: 3. Leaving the study early ‐ medium term.

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 3 Global impression: 3. Leaving the study early ‐ medium term.

4 Behaviour: 1. Not improved ‐ short term (OAS) Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.74]
Analysis 3.4
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 4 Behaviour: 1. Not improved ‐ short term (OAS).

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 4 Behaviour: 1. Not improved ‐ short term (OAS).

5 Mental state: 1. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed) Show forest plot

Other data

No numeric data
Analysis 3.5

Study

Intervention

mean

SD

N

Battaglia 1997

Lorazepam + haloperidol

17.50

10.18

32

Battaglia 1997

Lorazepam

24.20

10.02

31

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 5 Mental state: 1. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed).

6 Adverse events: 1. Extrapyramidal effects Show forest plot

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.94 [0.18, 20.30]
Analysis 3.6
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 6 Adverse events: 1. Extrapyramidal effects.

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 6 Adverse events: 1. Extrapyramidal effects.

7 Adverse events: 2. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 3.7
Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 7 Adverse events: 2. General.

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 7 Adverse events: 2. General.

7.1 ataxia

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [0.26, 8.11]

7.2 dizziness

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.12, 3.61]

7.3 dry mouth

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.15, 2.23]

7.4 speech disorder

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [0.26, 8.11]
Open in table viewer
Comparison 4. BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.79, 1.15]
Analysis 4.1
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

2 Global impression: 2. Leaving the study early ‐ medium term Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]
Analysis 4.2
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐7.26, 7.28]
Analysis 4.3
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor).

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor).

4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐1.93 [‐5.73, 1.87]
Analysis 4.4
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor).

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor).

5 Mental state: 3. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed) Show forest plot

Other data

No numeric data
Analysis 4.5

Study

Intervention

mean

SD

N

Battaglia 1997

Lorazepam + haloperidol

17.50

10.18

32

Battaglia 1997

Haloperidol

24.50

7.69

35

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 5 Mental state: 3. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed).

6 Adverse events: 1. Extrapyramidal effects Show forest plot

2

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.22, 0.94]
Analysis 4.6
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 6 Adverse events: 1. Extrapyramidal effects.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 6 Adverse events: 1. Extrapyramidal effects.

7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.25, 1.24]
Analysis 4.7
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

8 Adverse events: 3. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 4.8
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 8 Adverse events: 3. General.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 8 Adverse events: 3. General.

8.1 ataxia

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

3.28 [0.36, 29.97]

8.2 dizziness

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.13, 4.09]

8.3 dry mouth

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.24, 5.04]

8.4 speech disorder

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.20, 3.39]

9 Hospital and service outcome: Unfit for early discharge Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.9 [0.54, 1.50]
Analysis 4.9
Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 9 Hospital and service outcome: Unfit for early discharge.

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 9 Hospital and service outcome: Unfit for early discharge.

Open in table viewer
Comparison 5. SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Sedation ‐ medium term Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 5.1
Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 1 Global impression: 1. Sedation ‐ medium term.

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 1 Global impression: 1. Sedation ‐ medium term.

1.1 high

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.14]

1.2 low

2

203

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.47, 1.73]

2 Global impression: 2. Leaving the study early ‐ medium term Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 5.2
Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

2.1 high

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.14]

2.2 low

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

5.82 [0.62, 54.58]

3 Adverse events: Extrapyramidal effects Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 5.3
Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 3 Adverse events: Extrapyramidal effects.

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 3 Adverse events: Extrapyramidal effects.

3.1 high

2

56

Risk Ratio (M‐H, Fixed, 95% CI)

0.12 [0.02, 0.62]

3.2 low

2

204

Risk Ratio (M‐H, Fixed, 95% CI)

0.22 [0.05, 0.95]
Open in table viewer
Comparison 6. SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: Sedation ‐ medium term Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 6.1
Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 1 Global impression: Sedation ‐ medium term.

Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 1 Global impression: Sedation ‐ medium term.

1.1 randomised

4

231

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.34, 1.49]

1.2 unknown

2

93

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.45, 1.44]

2 Adverse events: 1. Extrapyramidal effects Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only
Analysis 6.2
Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 2 Adverse events: 1. Extrapyramidal effects.

Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 2 Adverse events: 1. Extrapyramidal effects.

2.1 randomised

6

351

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.07, 0.63]

2.2 unknown

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 0.65]

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.
Figuras y tablas -
Analysis 1.1

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 2 Global impression: 2. Sedation ‐ medium term.
Figuras y tablas -
Analysis 1.2

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 2 Global impression: 2. Sedation ‐ medium term.

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor).
Figuras y tablas -
Analysis 1.3

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor).

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 4 Global impression: 4. Leaving the study early ‐ medium term.
Figuras y tablas -
Analysis 1.4

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 4 Global impression: 4. Leaving the study early ‐ medium term.

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component).
Figuras y tablas -
Analysis 1.5

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component).

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor).
Figuras y tablas -
Analysis 1.6

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor).

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor).
Figuras y tablas -
Analysis 1.7

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor).

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 8 Adverse events: 1. Extrapyramidal effects.
Figuras y tablas -
Analysis 1.8

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 8 Adverse events: 1. Extrapyramidal effects.

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.
Figuras y tablas -
Analysis 1.9

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

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Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 10 Adverse events: 3. General.
Figuras y tablas -
Analysis 1.10

Comparison 1 BENZODIAZEPINES vs PLACEBO, Outcome 10 Adverse events: 3. General.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.
Figuras y tablas -
Analysis 2.1

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Sedation ‐ medium term.
Figuras y tablas -
Analysis 2.2

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Sedation ‐ medium term.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 3 Global impression: 3. Average score (CGI‐S, high = poor).
Figuras y tablas -
Analysis 2.3

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 3 Global impression: 3. Average score (CGI‐S, high = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor).
Figuras y tablas -
Analysis 2.4

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor).

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Study

Intervention

mean

SD

N

Chouinard 1993

Clonazepam

2.60

1.70

8

Chouinard 1993

haloperidol

2.80

0.60

8

Figuras y tablas -
Analysis 2.5

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 5 Global impression: 5. Average score ‐ medium term (CGI‐S, skewed).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 6 Global impression: 6. Leaving the study early ‐medium term.
Figuras y tablas -
Analysis 2.6

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 6 Global impression: 6. Leaving the study early ‐medium term.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 7 Behaviour: 1. Not improved ‐ medium term (OAS).
Figuras y tablas -
Analysis 2.7

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 7 Behaviour: 1. Not improved ‐ medium term (OAS).

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Study

Intervention

mean

SD

N

Subramaney 1998

Lorazepam

1.83

3.14

30

Subramaney 1998

Clothiapine

1.33

2.78

30

Figuras y tablas -
Analysis 2.8

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 8 Behaviour: 2. Average aggression score ‐ medium term (OAS, skewed).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 9 Mental state: 1. Not improved ‐ medium term (IMPS).
Figuras y tablas -
Analysis 2.9

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 9 Mental state: 1. Not improved ‐ medium term (IMPS).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 10 Mental state: 2. Average score (BPRS, high = poor).
Figuras y tablas -
Analysis 2.10

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 10 Mental state: 2. Average score (BPRS, high = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor).
Figuras y tablas -
Analysis 2.11

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor).
Figuras y tablas -
Analysis 2.12

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component).
Figuras y tablas -
Analysis 2.13

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor).
Figuras y tablas -
Analysis 2.14

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor).
Figuras y tablas -
Analysis 2.15

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor).

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 16 Adverse events: 1. Extrapyramidal effects.
Figuras y tablas -
Analysis 2.16

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 16 Adverse events: 1. Extrapyramidal effects.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.
Figuras y tablas -
Analysis 2.17

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

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Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 18 Adverse events: 3. General.
Figuras y tablas -
Analysis 2.18

Comparison 2 BENZODIAZEPINES vs ANTIPSYCHOTICS, Outcome 18 Adverse events: 3. General.

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.
Figuras y tablas -
Analysis 3.1

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 2 Global impression: 2. Not improved ‐ short term (CGI).
Figuras y tablas -
Analysis 3.2

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 2 Global impression: 2. Not improved ‐ short term (CGI).

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 3 Global impression: 3. Leaving the study early ‐ medium term.
Figuras y tablas -
Analysis 3.3

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 3 Global impression: 3. Leaving the study early ‐ medium term.

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 4 Behaviour: 1. Not improved ‐ short term (OAS).
Figuras y tablas -
Analysis 3.4

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 4 Behaviour: 1. Not improved ‐ short term (OAS).

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Study

Intervention

mean

SD

N

Battaglia 1997

Lorazepam + haloperidol

17.50

10.18

32

Battaglia 1997

Lorazepam

24.20

10.02

31

Figuras y tablas -
Analysis 3.5

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 5 Mental state: 1. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed).

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 6 Adverse events: 1. Extrapyramidal effects.
Figuras y tablas -
Analysis 3.6

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 6 Adverse events: 1. Extrapyramidal effects.

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Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 7 Adverse events: 2. General.
Figuras y tablas -
Analysis 3.7

Comparison 3 BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES, Outcome 7 Adverse events: 2. General.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.
Figuras y tablas -
Analysis 4.1

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 1 Global impression: 1. Need for additional medication ‐ medium term.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.
Figuras y tablas -
Analysis 4.2

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor).
Figuras y tablas -
Analysis 4.3

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor).

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor).
Figuras y tablas -
Analysis 4.4

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor).

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Study

Intervention

mean

SD

N

Battaglia 1997

Lorazepam + haloperidol

17.50

10.18

32

Battaglia 1997

Haloperidol

24.50

7.69

35

Figuras y tablas -
Analysis 4.5

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 5 Mental state: 3. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed).

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 6 Adverse events: 1. Extrapyramidal effects.
Figuras y tablas -
Analysis 4.6

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 6 Adverse events: 1. Extrapyramidal effects.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.
Figuras y tablas -
Analysis 4.7

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 8 Adverse events: 3. General.
Figuras y tablas -
Analysis 4.8

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 8 Adverse events: 3. General.

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Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 9 Hospital and service outcome: Unfit for early discharge.
Figuras y tablas -
Analysis 4.9

Comparison 4 BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS, Outcome 9 Hospital and service outcome: Unfit for early discharge.

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Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 1 Global impression: 1. Sedation ‐ medium term.
Figuras y tablas -
Analysis 5.1

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 1 Global impression: 1. Sedation ‐ medium term.

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Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.
Figuras y tablas -
Analysis 5.2

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 2 Global impression: 2. Leaving the study early ‐ medium term.

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Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 3 Adverse events: Extrapyramidal effects.
Figuras y tablas -
Analysis 5.3

Comparison 5 SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION, Outcome 3 Adverse events: Extrapyramidal effects.

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Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 1 Global impression: Sedation ‐ medium term.
Figuras y tablas -
Analysis 6.1

Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 1 Global impression: Sedation ‐ medium term.

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Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 2 Adverse events: 1. Extrapyramidal effects.
Figuras y tablas -
Analysis 6.2

Comparison 6 SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN, Outcome 2 Adverse events: 1. Extrapyramidal effects.

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Table 1. Drugs for rapid tranquillisation in London survey

Drug of choice

Mean dose

diazepam*

27 (10‐80)

haloperidol

22 (10‐60)

chlorpromazine

162 (50‐400)

droperidol

14 (10‐20)

paraldehyde

U/K

amytal

U/K

lorazepam

U/K

nitrazepam**

U/K

*most frequent

** least frequent
Figuras y tablas -
Table 1. Drugs for rapid tranquillisation in London survey
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Table 2. Preferred medication for rapid tranquillisation in Rio de Janeiro

Drug of choice

Mean dose

Frequency of use

haloperidol + promethazine

5 (2.5‐10) + 50 (25‐100)

61%

haloperidol + promethazine + diazepam

5 (2.5‐10) + 50 (25‐100) +10

15%

diazepam

10

9%

haloperidol + promethazine + chlorpromazine

5 + 50 + 25

7%

chlorpromazine + diazepam + promethazine

25 + 10 + 50

1%

chlorpromazine + promethazine

25 + 50

1%

chlorpromazine

25

1%

diazepam + promethazine

10 + 50

1%

haloperidol + diazepam

5 + 10

1%

promethazine

50

1%
Figuras y tablas -
Table 2. Preferred medication for rapid tranquillisation in Rio de Janeiro
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Table 3. High and low attrition studies

Attrition

Study

% loss

Duration

Notes

High

Barbee 1992

31

72 hours

Chouinard 1993

12

2 hours

Salzman 1991

33

48 hours

‐ for EPS outcome; 12% loss for 'sedation'

Low

Bienek 1998

0

7 days

Meehan 2001

4

24 hours

Solomon 1990

0

7 days

Subramaney 1998

0

7 days
Figuras y tablas -
Table 3. High and low attrition studies
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Comparison 1. BENZODIAZEPINES vs PLACEBO

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.66, 1.40]

2 Global impression: 2. Sedation ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

1.67 [0.42, 6.61]

3 Global impression: 3. Average change ‐ medium term (CGI‐S, high = poor) Show forest plot

1

76

Mean Difference (IV, Fixed, 95% CI)

0.07 [‐0.46, 0.60]

4 Global impression: 4. Leaving the study early ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.15, 2.38]

5 Mental state: 1. Remaining excited ‐ medium term (PANSS‐excited component) Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.40, 0.97]

6 Mental state: 2. Average change ‐ medium term (PANSS, high = poor) Show forest plot

1

99

Mean Difference (IV, Fixed, 95% CI)

‐2.57 [‐6.23, 1.09]

7 Mental state: 3. Average change ‐ medium term (PANSS‐excited component, high = poor) Show forest plot

1

101

Mean Difference (IV, Fixed, 95% CI)

‐1.91 [‐3.83, 0.01]

8 Adverse events: 1. Extrapyramidal effects Show forest plot

1

94

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.03, 2.96]

9 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.10]

10 Adverse events: 3. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 dizziness

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.89, 54.87]

10.2 nausea

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

9.0 [0.50, 162.97]

10.3 vomiting

1

102

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.32, 27.89]
Figuras y tablas -
Comparison 1. BENZODIAZEPINES vs PLACEBO
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Comparison 2. BENZODIAZEPINES vs ANTIPSYCHOTICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

2

216

Risk Ratio (M‐H, Random, 95% CI)

1.28 [0.51, 3.22]

2 Global impression: 2. Sedation ‐ medium term Show forest plot

6

324

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.48, 1.21]

3 Global impression: 3. Average score (CGI‐S, high = poor) Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Short term

1

16

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐0.58, 1.98]

3.2 Medium term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐0.62 [‐1.36, 0.12]

4 Global impression: 4. Average change ‐ medium term (CGI‐S, high = poor) Show forest plot

2

189

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.07, 0.47]

5 Global impression: 5. Average score ‐ medium term (CGI‐S, skewed) Show forest plot

Other data

No numeric data

6 Global impression: 6. Leaving the study early ‐medium term Show forest plot

4

254

Risk Ratio (M‐H, Random, 95% CI)

1.70 [0.11, 27.35]

7 Behaviour: 1. Not improved ‐ medium term (OAS) Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

2.6 [0.31, 22.05]

8 Behaviour: 2. Average aggression score ‐ medium term (OAS, skewed) Show forest plot

Other data

No numeric data

9 Mental state: 1. Not improved ‐ medium term (IMPS) Show forest plot

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.34, 6.70]

10 Mental state: 2. Average score (BPRS, high = poor) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

10.1 Short term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐3.26 [‐10.65, 4.13]

10.2 Medium term

1

37

Mean Difference (IV, Fixed, 95% CI)

‐4.07 [‐10.76, 2.62]

11 Mental state: 3. Average change ‐ medium term (BPRS, high = poor) Show forest plot

1

20

Mean Difference (IV, Fixed, 95% CI)

‐7.60 [‐13.87, ‐1.33]

12 Mental state: 4. Average change ‐ medium term (BPRS‐psychosis subscale, high score = poor) Show forest plot

1

66

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐4.65, 4.05]

13 Mental state: 5. Remaining excited ‐ medium term (PANSS‐excited component) Show forest plot

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

1.84 [1.06, 3.18]

14 Mental state: 6. Average change ‐ medium term (PANSS, high = poor) Show forest plot

1

146

Mean Difference (IV, Fixed, 95% CI)

5.64 [2.20, 9.08]

15 Mental state: 7. Average change ‐ medium term (PANSS‐Excited component, high = poor) Show forest plot

1

149

Mean Difference (IV, Fixed, 95% CI)

2.85 [1.14, 4.56]

16 Adverse events: 1. Extrapyramidal effects Show forest plot

7

391

Risk Ratio (M‐H, Fixed, 95% CI)

0.17 [0.06, 0.43]

17 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.03, 1.89]

18 Adverse events: 3. General Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1 ataxia

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

2.26 [0.22, 23.71]

18.2 dizziness

2

216

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [0.63, 3.07]

18.3 dry mouth

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

1.88 [0.49, 7.24]

18.4 nausea

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

7.76 [0.89, 67.67]

18.5 speech disorder

1

66

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.11, 2.87]

18.6 vomiting

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

13.46 [0.71, 255.70]
Figuras y tablas -
Comparison 2. BENZODIAZEPINES vs ANTIPSYCHOTICS
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Comparison 3. BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.79, 1.32]

2 Global impression: 2. Not improved ‐ short term (CGI) Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

1.47 [0.66, 3.25]

3 Global impression: 3. Leaving the study early ‐ medium term Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Behaviour: 1. Not improved ‐ short term (OAS) Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.74]

5 Mental state: 1. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed) Show forest plot

Other data

No numeric data

6 Adverse events: 1. Extrapyramidal effects Show forest plot

2

83

Risk Ratio (M‐H, Fixed, 95% CI)

1.94 [0.18, 20.30]

7 Adverse events: 2. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 ataxia

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [0.26, 8.11]

7.2 dizziness

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.12, 3.61]

7.3 dry mouth

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.15, 2.23]

7.4 speech disorder

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [0.26, 8.11]
Figuras y tablas -
Comparison 3. BENZODIAZEPINES + ANTIPSYCHOTICS vs BENZODIAZEPINES
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Comparison 4. BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Need for additional medication ‐ medium term Show forest plot

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.79, 1.15]

2 Global impression: 2. Leaving the study early ‐ medium term Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Mental state: 1. Average score ‐ medium term (BPRS, high = poor) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐7.26, 7.28]

4 Mental state: 2. Average score ‐ medium term (BPRS‐psychosis subscale, high = poor) Show forest plot

1

28

Mean Difference (IV, Fixed, 95% CI)

‐1.93 [‐5.73, 1.87]

5 Mental state: 3. Average change ‐ medium term (BPRS‐psychosis subscale, high = poor, skewed) Show forest plot

Other data

No numeric data

6 Adverse events: 1. Extrapyramidal effects Show forest plot

2

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.22, 0.94]

7 Adverse events: 2. Requiring anticholinergic medication ‐ medium term Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.25, 1.24]

8 Adverse events: 3. General Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 ataxia

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

3.28 [0.36, 29.97]

8.2 dizziness

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.13, 4.09]

8.3 dry mouth

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.24, 5.04]

8.4 speech disorder

1

67

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.20, 3.39]

9 Hospital and service outcome: Unfit for early discharge Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.9 [0.54, 1.50]
Figuras y tablas -
Comparison 4. BENZODIAZEPINES + ANTIPSYCHOTICS vs ANTIPSYCHOTICS
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Comparison 5. SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: 1. Sedation ‐ medium term Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 high

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.14]

1.2 low

2

203

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.47, 1.73]

2 Global impression: 2. Leaving the study early ‐ medium term Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 high

1

16

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.02, 7.14]

2.2 low

1

150

Risk Ratio (M‐H, Fixed, 95% CI)

5.82 [0.62, 54.58]

3 Adverse events: Extrapyramidal effects Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 high

2

56

Risk Ratio (M‐H, Fixed, 95% CI)

0.12 [0.02, 0.62]

3.2 low

2

204

Risk Ratio (M‐H, Fixed, 95% CI)

0.22 [0.05, 0.95]
Figuras y tablas -
Comparison 5. SENSITIVITY ANALYSIS: 1. HIGH vs LOW ATTRITION
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Comparison 6. SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Global impression: Sedation ‐ medium term Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 randomised

4

231

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.34, 1.49]

1.2 unknown

2

93

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.45, 1.44]

2 Adverse events: 1. Extrapyramidal effects Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 randomised

6

351

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.07, 0.63]

2.2 unknown

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 0.65]
Figuras y tablas -
Comparison 6. SENSITIVITY ANALYSIS: 2. RANDOMISED vs UNKNOWN
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