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Meta-Analysis
. 2012 Nov 14;11(11):CD006391.
doi: 10.1002/14651858.CD006391.pub2.

Benzodiazepines for schizophrenia

Markus Dold  1 , Chunbo Li, Magdolna Tardy, Vesal Khorsand, Donna Gillies, Stefan Leucht
Affiliations
Meta-Analysis

Benzodiazepines for schizophrenia

Markus Dold et al. Cochrane Database Syst Rev. .

Abstract

Background: Because of the high number of people with schizophrenia not responding adequately to monotherapy with antipsychotic agents, the evidence regarding the efficacy and safety of additional medication was examined in a number of clinical trials. One approach to this research question was the use of benzodiazepines, as monotherapy as well as in combination with antipsychotics.

Objectives: To determine the efficacy, acceptability, and tolerability of benzodiazepines in people with schizophrenia and schizophrenia-like psychoses.

Search methods: In February 2011, we updated the literature search of the previous version of this systematic review (last search March 2005). We searched the trial register of the Cochrane Schizophrenia Group (containing methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings). Additionally, we inspected references of all identified studies for further relevant studies and contacted authors of relevant publications in order to obtain missing data from existing trials. We applied no language restrictions.

Selection criteria: We included all randomised controlled trials comparing benzodiazepines (as monotherapy or as adjunctive agent) with antipsychotic drugs or placebo for the pharmacological management of schizophrenia and/or schizophrenia-like psychoses.

Data collection and analysis: Review authors (MD and CL) analysed independently the new references of the update-search referring to the inclusion criteria. MD and CL extracted all data from the included trials. For dichotomous outcomes we calculated risk ratios (RR) and their 95% confidence intervals (CI). We analysed continuous data by using mean differences (MD) and their 95% CI. We assessed each pre-selected outcome from the included trials with the risk of bias tool.

Main results: The 2011 update search yielded three further randomised controlled trials. The review currently includes 34 studies with 2657 participants. Most studies were characterised by a small sample size, short duration, and incomplete outcome data reporting.Benzodiazepine monotherapy is compared with placebo in eight trials. The proportion of participants with no clinically important response did not significantly differ between those given benzodiazepines or placebo (N = 382, 6 RCTs, RR 0.67 CI 0.44 to 1.02). The results from the various rating scales applied to assess global and mental state were inconsistent.Fourteen studies examined benzodiazepine monotherapy in comparison with antipsychotic monotherapy. Clinically important treatment response assessment revealed no statistically significant difference between the study groups (30 minutes: N = 44, 1 RCT, RR 0.91 CI 0.58 to 1.43; 60 minutes: N = 44,1 RCT, RR 0.61 CI 0.20 to 1.86; 12 hours: N = 66, 1 RCT, RR 0.75 CI 0.44 to 1.30; pooled short-term studies: N = 112, 2 RCTs, RR 1.48 CI 0.64 to 3.46). Desired sedation occurred significantly more often among participants in the benzodiazepine group than in the antipsychotic group at 20 and 40 minutes. No significant between-group differences could be identified for global and mental state or occurrence of adverse effects.Twenty trials compared benzodiazepine augmentation of antipsychotics with antipsychotic monotherapy. Referring to clinically important response, statistically significant improvement could be demonstrated only for the first 30 minutes of augmentation treatment (30 minutes: 1 RCT, N = 45, RR 0.38 CI 0.18 to 0.80; 60 minutes: N = 45,1 RCT, RR 0.07 CI 0.00 to 1.13; 12 hour: N = 67,1 RCT, RR 0.85 CI 0.51 to 1.41; pooled short-term studies: N = 511, 6 RCTs, RR 0.87 CI 0.49 to 1.54). Analyses of the global and mental state yielded no between-group differences except for desired sedation at 30 as well as 60 minutes (30 minutes: N = 45, 1 RCT, RR 2.25 CI 1.18 to 4.30; 60 minutes: N = 45, 1 RCT, RR 1.39 CI 1.06 to 1.83).

Authors' conclusions: There is currently no convincing evidence to confirm or refute the practise of administering benzodiazepines as monotherapy or in combination with antipsychotics for the pharmacological treatment of schizophrenia and schizophrenia-like psychosis. Low-quality evidence suggests that benzodiazepines are effective for very short-term sedation and could be considered for calming acutely agitated people with schizophrenia. Measured by the overall attrition rate, the acceptability of benzodiazepine treatment appears to be adequate. Adverse effects were generally poorly reported. High-quality future research projects with large sample sizes are required to clarify the evidence of benzodiazepine treatment in schizophrenia, especially regarding long-term augmentation strategies.

PubMed Disclaimer

Conflict of interest statement

Markus Dold: received travel payment from Janssen‐Cilag. Magdolna Tardy: none to declare. Chunbo Li: none to declare. Vesal Khorsand: none to declare. Donna Gillies: none to declare. Stefan Leucht: has received honoraria for consulting/advisory boards from Alkermes, BristolMyersSquibb, EliLilly, Janssen, Johnson&Johnson, Medavante, Roche, lecture honoraria from AstraZeneca, BristolMyersSquibb, EliLilly, EssexPharma, Janssen, Johnson&Johnson, Lundbeck Institute, Pfizer, SanofiAventis, and EliLilly has provided medication for a trial with SL as the primary investigator.

Figures

1
1
Study flow diagram.
2
2
3
3
1.1
1.1. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 1 No clinically important response to treatment ‐ short term.
1.2
1.2. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 2 Leaving the study early ‐ any reason.
1.3
1.3. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 3 Leaving the study early due to adverse effects.
1.4
1.4. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 4 Leaving the study early due to inefficacy of treatment.
1.5
1.5. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 5 Global state: 1. Relapse.
1.6
1.6. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 6 Mental state: 1. General ‐ various scales (unimproved or worse) ‐ short term.
1.7
1.7. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 7 Mental state: 2. General mean BPRS at 3 weeks (high=poor) ‐ short term.
1.8
1.8. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 8 Mental state: 3a. Specific ‐ anxiety TSRS at 6 weeks (unimproved or worse) ‐ short term.
1.10
1.10. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 10 Adverse effects: 1. total number of participants with adverse effects ‐ short term.
1.11
1.11. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 11 Adverse effects: 2. Anorexia ‐ short term.
1.12
1.12. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 12 Adverse effects: 3. Autonomic reaction (flushing, dryness of mouth etc) ‐ short term.
1.13
1.13. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 13 Adverse effects: 4. Cardiovascular reactions ‐ short term.
1.14
1.14. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 14 Adverse effects: 5. Depression ‐ short term.
1.15
1.15. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 15 Adverse effects: 6. Dryness of mouth ‐ short term.
1.16
1.16. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 16 Adverse effects: 7. Energy level change ‐ short term.
1.17
1.17. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 17 Adverse effects: 8. Gastrointestinal reactions ‐ short term.
1.18
1.18. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 18 Adverse effects: 9. Headache ‐ short term.
1.19
1.19. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 19 Adverse effects: 10. Insomnia ‐ short term.
1.20
1.20. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 20 Adverse effects: 11. Movement disorders ‐ short term.
1.21
1.21. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 21 Adverse effects: 12. Sedation (extreme) ‐ short term.
1.22
1.22. Analysis
Comparison 1 BENZODIAZEPINES AS SOLE TREATMENT versus PLACEBO AS SOLE TREATMENT, Outcome 22 Sensitivity analysis (no clinically important response to treatment) ‐ use of fixed‐effects model.
2.1
2.1. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 1 No clinically important response to treatment ‐ ultra short term.
2.2
2.2. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 2 No clinically important response to treatment ‐ short term.
2.3
2.3. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 3 Leaving the study early ‐ any reason.
2.4
2.4. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 4 Leaving the study early due to adverse effects.
2.5
2.5. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 5 Leaving the study early due to inefficacy of treatment.
2.6
2.6. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 6 Global state: 2a. Mean CGI severity score ‐ ultra short term (high=poor).
2.8
2.8. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 8 Global state: 3. Relapse.
2.9
2.9. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 9 Mental state: 1. General (various scales) ‐ short term.
2.10
2.10. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 10 Mental state: 2a. General ‐ BPRS ‐ ultra short term (high=poor).
2.13
2.13. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 13 Mental state: 3b. Specific ‐ sedation ‐ ultra short term (high=better).
2.14
2.14. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 14 Mental state: 3c. Specific ‐ sedation, mean CGI sedation score ‐ ultra short term (at 2 hours) (high=poor).
2.16
2.16. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 16 Behaviour: 2a. Specific ‐ aggression ‐ ultra short term.
2.17
2.17. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 17 Behaviour: 2b. Specific ‐ aggression ‐ ultra short term.
2.18
2.18. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 18 Service use: 1. Still in hospital ‐ short term (after 2 weeks).
2.19
2.19. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 19 Adverse effects: 1. total number of participants with adverse‐effects.
2.20
2.20. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 20 Adverse effects: 2. Anorexia ‐ short term.
2.21
2.21. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 21 Adverse effects: 3.Cardiovascular reactions ‐ short term.
2.22
2.22. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 22 Adverse effects: 4. Change in energy level ‐ short term.
2.23
2.23. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 23 Adverse effects: 5. Depression ‐ short term.
2.24
2.24. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 24 Adverse effects: 6. Dizziness ‐ ultra short term.
2.25
2.25. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 25 Adverse effects: 7. Dryness of mouth.
2.26
2.26. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 26 Adverse effects: 8. Gastric reactions ‐ short term.
2.27
2.27. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 27 Adverse effects: 9. Headaches ‐ short term.
2.28
2.28. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 28 Adverse effects: 10. Insomnia ‐ short term.
2.29
2.29. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 29 Adverse effects: 11a. Movement disorders.
2.31
2.31. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 31 Adverse effects: 12. Respiratory depression ‐ ultra short term.
2.32
2.32. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 32 Adverse effects: 13. Sedation (extreme) ‐ ultra short term.
2.33
2.33. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 33 Adverse effects: 14. Seizure ‐ ultra short term.
2.34
2.34. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 34 Sensitivity analysis (no clinically important response to treatment, ultra short term) ‐ use of a fixed‐effects model.
2.35
2.35. Analysis
Comparison 2 BENZODIAZEPINES versus ANTIPSYCHOTICS, Outcome 35 Sensitivity analysis (no clinically important response to treatment, short term) ‐ use of a fixed‐effects model.
3.1
3.1. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 1 No clinically important response to treatment ‐ ultra short term.
3.2
3.2. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 2 No clinically important response to treatment ‐ short term.
3.3
3.3. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 3 Leaving the study early any reason.
3.4
3.4. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 4 Leaving the study early due to adverse effects ‐ short term.
3.5
3.5. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 5 Leaving the study early due to inefficacy of treatment ‐ short term.
3.7
3.7. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 7 Mental state: 1. General ‐ ultra short term (various scales).
3.8
3.8. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 8 Mental state: 1. General ‐ short term (various scales).
3.11
3.11. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 11 Mental state: 3. Specific ‐ sedation ‐ ultra short term.
3.12
3.12. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 12 Behaviour: 1. Specific ‐aggression ‐ ultra short term (needing restraints within 120 minutes).
3.13
3.13. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 13 Behaviour: 2. Specific ‐ aggression ‐ ultra short term.
3.14
3.14. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 14 Service use: 1. Still in hospital ‐ short term (at 3 days).
3.15
3.15. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 15 Adverse effects: 1. total number of participants with adverse‐effects.
3.16
3.16. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 16 Adverse effects: 2. TESS score ‐ short term.
3.17
3.17. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 17 Adverse effects: 3. Anorexia ‐ short term.
3.18
3.18. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 18 Adverse effects: 4. Allergic reaction ‐ short term.
3.19
3.19. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 19 Adverse effects: 5. Blurred vision ‐ short term.
3.20
3.20. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 20 Adverse effects: 6. Cardiovascular reactions ‐ short term.
3.21
3.21. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 21 Adverse effects: 7. Chills ‐ short term.
3.22
3.22. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 22 Adverse effects: 8. Confusion ‐ short term.
3.23
3.23. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 23 Adverse effects: 9. Depression ‐ short term.
3.24
3.24. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 24 Adverse effects: 10. Diarrhoea ‐ short term.
3.25
3.25. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 25 Adverse effects: 11. Dizziness.
3.26
3.26. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 26 Adverse effects: 12. Drowsiness.
3.27
3.27. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 27 Adverse effects: 13. Dryness of mouth.
3.28
3.28. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 28 Adverse effects: 14. Excitation ‐ short term.
3.29
3.29. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 29 Adverse effects: 15. Gastrointestinal reactions ‐ short term.
3.30
3.30. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 30 Adverse effects: 16. Headache ‐ short term.
3.31
3.31. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 31 Adverse effects: 17. Increased salivation ‐ short term.
3.32
3.32. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 32 Adverse effects: 18. Insomnia ‐ short term.
3.33
3.33. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 33 Adverse effects: 19. Lactation ‐ short term.
3.34
3.34. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 34 Adverse effects: 20. Movement disorders.
3.35
3.35. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 35 Adverse effects: 21. Restlessness ‐ short term.
3.36
3.36. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 36 Adverse effects: 22. Sensory disturbances ‐ short term.
3.37
3.37. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 37 Adverse effects: 23. Sleep disorder ‐ short term.
3.38
3.38. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 38 Adverse effects: 24. Somnolence ‐ short term.
3.39
3.39. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 39 Adverse effects: 25. Vomitting ‐ short term.
3.40
3.40. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 40 Sensitivity analysis (no clinically important response to treatment, ultra short term) ‐ exclusion of studies which were not double‐blind‐effects model.
3.41
3.41. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 41 Sensitivity analysis (no clinically important response to treatment, ultra short term) ‐ use of a fixed‐effects model.
3.42
3.42. Analysis
Comparison 3 ADJUNCTIVE BENZODIAZEPINES + ANTIPSYCHOTICS versus PLACEBO/NO ADJUNCTIVE TREATMENT + ANTIPSYCHOTICS, Outcome 42 Sensitivity analysis (no clinically important response to treatment, short term) ‐ use of a fixed‐effects model.
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References

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Gundlach 1966 {published data only}
    1. Gundlach R, Engelhardt DM, Hankoff L, Paley H, Rudorfer L, Bird E. A Double‐blind outpatient study of diazepam (Valium) and placebo. Psychopharmacologia 1966;9:81‐92. - PubMed
Guz 1972 {published data only}
    1. Guz I. Lorazepam and haloperidol in the treatment of schizophrenic patients [Lorazepam e haloperidol em esquizofrenia]. Jornal Brasileiro de Psiquiatria 1988;37:205‐7.
    1. Guz I, Moraes R, Sartoretto JN. The therapeutic effects of lorazepam in psychotic patients treated with haloperidol ‐ A double blind study. Current Therapeutic Research 1972;14:767‐74. - PubMed
Hankoff 1962 {published data only}
    1. Hankoff L, Rudorfer L, Paly HM. A reference study of ataraxics. A two‐week double blind outpatient evaluation. The Journal of New Drugs 1962;179:173‐8. - PubMed
Hanlon 1969 {published data only}
    1. Hanlon TE, Kay Y, Agallianos D, Berman A, Bethon C, Kolber F, et al. Combined drug treatment of newly hospitalized, acutely ill psychiatric patients. Diseases of the Nervous System 1969;30:104‐16. - PubMed
Hanlon 1970 {published data only}
    1. Hanlon TE, Ota KY, Kurland AA. Comparative effects of fluphenazine, fluphenazine‐chlordiazepoxide and fluphenazine‐imipramine. Diseases of the Nervous System 1970;31:171‐7. - PubMed
    1. Hanlon TE, Robert JB, Kurland AA. Effects od control techniques on therapeutic outcome in a controlled trial. International Pharmacopsychiatry 1975;10:169‐76. - PubMed
Holden 1968 {published data only}
    1. Holden JMC, Holden UP. Weight changes with schizophrenic psychosis and psychotropic drug therapy. Psychosomatics 1970;11:551‐61. - PubMed
    1. Holden JMC, Itil TM. Laboratory changes with chlordiazepoxide and thioridazine, alone and combined. Canadian Psychiatric Association Journal 1969;14:299‐301. - PubMed
    1. Holden JMC, Itil TM, Keskiner A, Fink M. Thioridazine and chlordiazepoxide, alone and combined, in the treatment of chronic schizophrenia. Comprehensive Psychiatry 1968;9:633‐43. - PubMed
Kurland 1966 {published data only}
    1. Kurland AA, Bethon GD, Michaux MH, Agallianos DD. Chlorpromazine‐chlordiazepoxide and chlorpromazine‐imipramine treatment: side effects and clinical laboratory findings. Journal of New Drugs 1966;6:80‐95. - PubMed
    1. Michaux MH, Kurland AA, Agallianos DD. Chlorpromazine‐chlordiazepoxide and chlorpromazine‐imipramine treatment of newly hospitalized, acutely ill psychiatric patients. Current Therapeutic Research Clininical and Experimental 1966;8(Suppl):117‐52. - PubMed
Kutcher 1989 {published data only}
    1. Kutcher S, Williamson P, MacKenzie S, Marton P, Ehrlich M. Successful clonazepam treatment of neuroleptic‐induced akathisia in older adolescents and young adults: a double‐blind, placebo‐controlled study. Journal of Clinical Psychopharmacology 1989;9:403‐6. - PubMed
Lerner 1979 {published data only}
    1. Lerner Y, Lwow E, Levitin A, Belmaker RH. Acute high‐dose parenteral haloperidol treatment of psychosis. American Journal of Psychiatry 1979;136:1061‐4. - PubMed
Lingjaerde 1979 {published data only}
    1. Lingjaerde O, Engstrand E, Ellingsen P, Robak OH. Antipsychotic effect of diazepam when given in addition to neuroleptics in chronic psychotic patients ‐ A double‐blind clinical trial. Current Therapeutic Research 1979;26:505‐14.
Lingjaerde 1982 {published data only}
    1. Lingjaerde O. Effect of the benzodiazepine derivative estazolam in patients with auditory hallucinations. A multicentre double‐blind, cross‐over study. Acta Psychiatrica Scandinavia 1982;65:339‐54. - PubMed
Ma 2006 {published data only}
    1. Ma C. The control study of injection of clonazepam into tinggong for auditory hallucination of schizophrenia. Journal of Clinical Psychosomatic Diseases 2006;12:338‐9.
Marneros 1979 {published data only}
    1. Marneros A. Anxiolytische Zusatzbehandlung bei den affektbetonten Schizophrenien. Ein Doppelblindversuch. Therapiewoche 29 1979;44:7533‐8.
Merlis 1962 {published data only}
    1. Merlis S, Turner WJ, Krumholz W. A double‐blind comparison of diazepam, chlordiazepoxide and chlorpromazine in psychotic patients. Journal of Neuropsychiatry 1962;3:133‐8. - PubMed
Minervini 1990 {published data only}
    1. Minervini MG, Priore P, Farolfi A, Cesana B, Morselli PL. Double blind, controlled study of the efficacy and safety of alpidem in the treatment of anxiety in schizophrenic in‐patients. Pharmacopsychiatry 1990;23:102‐6. - PubMed
Morphy 1986 {published data only}
    1. Morphy M. A double‐blind comparison of alprazolam and placebo in the treatment of anxious schizophrenic outpatients. Current Therapeutic Research 1986;40:551‐60.
Nestoros 1982 {published data only}
    1. Nestoros JN, Suranyi‐Cadotte BE, Spees RC, Schwartz G, Vasavan Nair NP. Diazepam in high doses is effective in schizophrenia. Progress in Neuro‐ Psychopharmacolgy and Biological Psychiatry 1982;6:513‐6. - PubMed
Nishikawa 1982 {published data only}
    1. Nishikawa T, Tsuda A, Tanaka M, Koga I, Uchida Y. Prophylactic effect of neuroleptics in symptom‐free schizophrenics. Psychopharmacology 1982;77:301‐4. - PubMed
Pujalte 1994 {published data only}
    1. Pujalte D, Battai T, Hue B, Alric R, Pouget R, Blayac JP, et al. A double‐blind comparison of clonazepam and placebo in the treatment of neuroleptic‐induced akathisia. Clinical Neuropharmacology 1994;17:236‐42. - PubMed
Stevens 1992 {published data only}
    1. Stevens A, Stevens I, Mahal A, Gaertner HJ. Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis. Pharmacopsychiatry 1992;25:273‐7. - PubMed
TREC‐Rio 2003 {published data only}
    1. TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethiazine. BMJ 2003;327:708‐13. - PMC - PubMed
Wang 2000 {published data only}
    1. Wang G, Ji R, Pei G. the control study of injection of clonazepam into t´ingkung for refractory auditory hallucination of schizophrenics. Journal of Clinical Psychosomatic Diseases 2000;6:143‐4.
Wang 2003 {published data only}
    1. Wang X, Wang X, Zhou H. An efficacy study of risperidone combined with clonazepam injection in the treatment of paranoid schizophrenia. Journal of Clinical Psychologic Medicine 2003;13:217‐8.
Wyant 1990 {published data only}
    1. Wyant M, Diamond BI, O'Neal E, Sloan A, Borison RL. The use of midazolam in acutely agitated psychiatric patients. Psychopharmacology Bulletin 1990;26:126‐9. - PubMed
Xuan 2007 {published data only}
    1. Xuan GH, Chu Y. Clinical observation on the effect of risperidone combined with BZD on schizophrenia. China Tropical Medicine 2007;7:244.

References to studies excluded from this review

Adler 1985 {published data only}
    1. Adler L, Angrist B, Peselow E, Corwin J, Rotrosen J. Efficacy of propranolol in neuroleptic‐induced akathisia. Journal of Clinical Psychopharmacology 1985;5:164‐6. - PubMed
Alexander 2004 {published data only}
    1. Alexander J, Tharyan P, Adams C, John T, Mol C, Philip J. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. British Journal of Psychiatry 2004;186:63‐9. - PubMed
Altamura 1987 {published data only}
    1. Altamura AC, Mauri MC, Mantero M, Brunetti M. Clonazepam/haloperidol combination therapy in schizophrenia: A double blind study. Acta Psychiatrica Scandinavica 1987;76:702‐6. - PubMed
Ananth 1979 {published data only}
    1. Ananth JV, Sohn JH, Ban TA, Lehmann HE. Doxepin in geriatric patients. Current Therapeutic Research 1979;25:133‐8.
Bao 2007 {published data only}
    1. Bao LY, Wang KM. The effectiveness of aripiprazole combined with clonazepam treated with agitation in schizophrenia. Medical Journal of Chinese People's Health 2007;5:ni.
Bienek 1997 {published data only}
    1. Bienek SA, Ownby RL, Dominguez RA. A double‐blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy 1998;18:57‐62. - PubMed
Bobruff 1981 {published data only}
    1. Bobruff A, Gardos G, Tarsy D, Rapkin R, Cole J, Moore P. Clonazepam and phenobarbital in tardive dyskinesia. American Journal of Psychiatry 1981;138:189‐93. - PubMed
Cohen 1987 {published data only}
    1. Cohen S, Khan A. Adjunctive benzodiazepines in acute schizophrenia. Neuropsychobiology 1987;18:9‐12. - PubMed
Crosse 1974 {published data only}
    1. Crosse B. Clinical trials of sulpiride (1403 R.D.‐‐Dogmatil): Its advantages prescribed alone or in combination [Essais cliniques du sulpiride (1403 R. D. ‐ Dogmatil): Son Intérêt en prescription isolée et en association]. Psychologie Médicale 1974;6:1623‐30.
Csernansky 1988 {published data only}
    1. Csernansky JG, Riney SJ, Lombrozo L, Overall JE, Hollister LE. Double‐blind comparison of alprazolam, diazepam, and placebo for the treatment of negative symptoms. Archive of General Psychiatry 1988;45:655‐9. - PubMed
    1. Csernansky JG, Tacke U, Rusen D, Hollister LE. The effect of benzodiazepines on tardive dyskinesia symptoms. Journal of Clinical Psychopharmacology 1988;8:154. - PubMed
Dubin 1988 {published data only}
    1. Dubin WR. Rapid tranquilization: antipsychotics or benzodiazepines. Journal of Clinical Psychiatry 1988;49:5‐11. - PubMed
Ge Qianrong 2004 {published data only}
    1. Ge Q, Liang X, Wang X. A comparative study of risperidone combining clonazepam and haloperidol in the treatment of patients with schizophrenia. Shandong Archives of Psychiatry 2004;17:134‐6.
Greenfeld 1987 {published data only}
    1. Greenfeld D, Conrad C, Kincare P, Bowers MB. Treatment of catatonia with low‐dose lorazepam. American Journal of Psychiatry 1987;144:1224‐5. - PubMed
Haas1982 {published data only}
    1. Haas S, Emrich HM, Beckmann H. Analgesic and euphoric effects of high dose diazepam in schizophrenia. Neuropsychobiology 1982;8:123‐8. - PubMed
Hanus 1973 {published data only}
    1. Hanus M, Guelfi J. A new tranquilizer: lorazepam (158 cases) [Un nouveau tranquillisant: le Lorazepam (158 observations)]. Semaine des Hopitaux (Therapeutique) 1973;49:349‐54. - PubMed
Hartelius 1978 {published data only}
    1. Hartelius H, Larsson AK, Lepp M, Malm U, Arvidsson A, Dahlstrom H. A controlled long‐term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects. Acta Psychiatrica Scandinavica 1978;58:1‐15. - PubMed
Harvey 2004 {published data only}
    1. Harvey AT, Flockhart D, Gorski JC, Greenblatt DJ, Burke M, Werder S, et al. Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia. Journal of Clinical Pharmacology 2004;44:1173‐84. - PubMed
He 2007 {published data only}
    1. He W. [Title only available in Chinese characters]. Modern Medicine and Health 2007;23:527.
Hekimian 1967 {published data only}
    1. Hekimian LJ, Friedhoff AJ. A controlled study of placebo, chlordiazepoxide and chlorpromazine with thirty male schizophrenic patients. Diseases of Nervous System 1967;28:675‐8. - PubMed
Hesso 1975 {published data only}
    1. Hesso R, Retterstol N, Torp H. Clinical trial with a new substance (PLP 100‐127) in order to asses therapeutic efficacy and dependence creating properties. Behavioral Neuropsychiatry 1975;7:13‐7. - PubMed
Horiguchi 1992 {published data only}
    1. Horiguchi J, Nishimatsu O. Usefulness of antiparkinsonian drugs during neuroleptic treatment and the effect of clonazepam on akathisia and parkinsonism occurred after antiparkinsonian drug withdrawal: a double‐blind study. Japanese Journal of Psychiatry and Neurology 1992;46:733‐9. - PubMed
Hovens 2005 {published data only}
    1. Hovens JE, Dries PJT, Melman CTM, Wapenaar RJC, Loonen AJM. Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open‐label study. Journal of Psychopharmacology 2005;19:51‐7. - PubMed
Hu 2004 {published data only}
    1. Hu W. Investigation of administering BZD medicament in outpatients with psychosis. Heath Psychology Journal 2004;12:43.
Itil 1972 {published data only}
    1. Itil T, Gannon P, Cora R, Polvan N, Akpinar S, Elveris F, et al. SCH‐12,041, a new anti‐anxiety agent (quantitative pharmaco‐electroencephalography and clinical trials). Behavioral Neuropsychiatry 1972;4:15‐24. - PubMed
Jibiki 1994 {published data only}
    1. Jibiki I, Yamaguchi N, Momonoi F. Beneficial effect of high‐dose clotiazepam on intractable auditory hallucinations in chronic schizophrenic patients. An open trial. European Journal of Clinical Pharmacology 1994;46:367‐9. - PubMed
Jirmeson 1982 {published data only}
    1. Jimerson DC, Kammen DP, Post RM, Docherty JP, Bunney WE. Diazepam in schizophrenia: a preliminary double‐blind trial. American Journal of Psychiatry 1982;139:489‐91. - PubMed
Jungkunz 1984 {published data only}
    1. Jungkunz G, Nedopil N, Ruther E. Acute effects of the synthetic analogue of methionine enkephalin FK 33‐824 in schizophrenic patients. A double blind trial. Pharmacopsychiatry 1984;17:76‐8. - PubMed
Kang 2006 {published data only}
    1. Kang M. Clinical study on efficacy of quetiapine combined with clonazepam treated with acute agitation in schizophrenia patients. Linchuang Jingshen Yixue Zazhi 2006;16:221‐2.
Karson 1982 {published data only}
    1. Karson C, Weinberger D, Bigelow L, Wyatt RJ. Clonazepam treatment of chronic schizophrenia: negative results in a double‐blind, placebo‐controlled trial. American Journal of Psychiatry 1982;139:1627‐8. - PubMed
Kellner 1975 {published data only}
    1. Kellner R, Wilson RM, Muldawer MD, Pathak D. Anxiety in schizophrenia. The responses to chlordiazepoxide in an intensive design study. Archives of General Psychiatry 1975;32:1246‐54. - PubMed
Knott 2006 {published data only}
    1. Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Annals of Emergency Medicine 2006;47:61‐7. - PubMed
Li 2004 {published data only}
    1. Li AF. [Title only available in Chinese characters]. Chinese Journal of Clinical Medicine 2004;3:33‐4.
Li 2007 {published data only}
    1. Li C, Zhu S, Wang H, Chen H, Yu Y, Liu D, et al. Safety and efficacy of clonazepam, haloperidol and haloperidol combined with clonazepam in the treatment of schizophrenia with excitement and agitation. Shanghai Archives of Psychiatry 2007;19:150‐2.
Maar 1983 {published data only}
    1. Maar S, Schuback G. Comparison of two benzodiazepines in general psychosomatic disturbances [Wirkungsvergleich zweier Benzodiazepine bei psychovegetativen Allgemeinstörungen]. Therapiewoche 1983;33:1251‐8.
Mei 2006 {published data only}
    1. Mei Y, Pan J, Ma P. Clinical observation on acute excitation of schizophrenia treated with QIWEI combined with clonazepam. Chinese Nursing Research 2006;20:1176‐7.
Monroe 1967 {published data only}
    1. Monroe RR, Dale R. Chlordiazepoxide in the treatment of patients with "activated EEG's". Diseases of Nervous System 1967;28:390‐6. - PubMed
Nestros 1983 {published data only}
    1. Nestros JN, Nair NPV, Pulman JR, Schwartz G, Bloom D. High doses of diazepam improve neuroleptic‐resistant chronic schizophrenic patients. Psychopharmacology 1983;81:42‐7. - PubMed
Nobay 2004 {published data only}
    1. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective, double‐blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Academic Emergency Medicine 2004;11:744‐9. - PubMed
Pato 1989 {published data only}
    1. Pato CN, Wolkowitz OM, Rapaport M, Schulz SC, Pickar D. Benzodiazepine augmentation of neuroleptic treatment in patients with schizophrenia. Psychopharmacology Bulletin 1989;25:263‐6. - PubMed
Pecknold 1993 {published data only}
    1. Pecknold JC. Survey of the adjuvant use of benzodiazepines for treating outpatients with schizophrenia. The Journal of Psychiatric Neurosciences 1993;18:82‐4. - PMC - PubMed
Qin 2005 {published data only}
    1. Qin Y, Kang W, Song L. A comparative study of risperidone combining alprazolam and clozapine in the treatment of patients with schizophrenia. Heath Psychology Journal 2005;13:444‐5.
Remington 1993 {published data only}
    1. Remington G, Fornazzari L, Setha R. Placebo response in refractory tardive akathisia. Canadian Journal of Psychiatry 1993;38:248‐9. - PubMed
Richards 1998 {published data only}
    1. Richards JR, Derlet RW, Duncan DR. Chemical restraint for the agitated patient in the emergency department: lorazepam versus droperidol. The Journal of Emergency Medicine 1998;16:567‐73. - PubMed
Ruskin 1978 {published data only}
    1. Ruskin P, Averbush I, Belmaker RH, Dasberg H. Benzodiazepind in chronic schizophrenia. Biological Psychiatry 1979;14:557‐8. - PubMed
Salam 1988 {published data only}
    1. Salam SA, Kilzieh N. Lorazepam treatment of psychogenic catatonia: an update. Journal of Clinical Psychiatry 1988;49:16‐21. - PubMed
Saletu 1971 {published data only}
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Shafti 2005 {published data only}
    1. Shafti SS. Rehabilitation of schizophrenia: adjunctive therapy of negative symptoms. Iranian Rehabilitation Journal 2004;2:ni.
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Soldatos 1986 {published data only}
    1. Soldatos CR, Sakkas PN, Bergiannaki JD, Stefanis CN. Behavioral side effects of triazolam in psychiatric inpatients: report of five cases. Drug Intelligence and Clinical Pharmacy 1986;20:294‐7. - PubMed
Sterlin 1971 {published data only}
    1. Sterlin C, Augustin E, Ban TA, Jarrold L. Doxepin as adjuvant medication in the treatment of chronic schizophrenic patients: a comparative study. Current Therapy Research Clinical and Experimental 1971;13:50‐2. - PubMed
Stonehill 1966 {published data only}
    1. Stonehill E, Lee H, Ban TA. A comparative study with Benzodiazepines in chronic psychotic patients. Diseases of the Nervous System 1966;27:411‐3. - PubMed
Subramaney 1997 {published data only}
    1. 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. 10th ECNP (European College of Neuropsychopharmacology) Congress, Vienna, Austria Sep 13 ‐ 17, 1997.
Tang 2007 {published data only}
    1. Tang Q, Yang L, Lai G, Zhand J. A clinical study of risperidone oral solution combined with clonazepam injection in the treatment of acute excitement phase schizophrenia patient. Shanghai Archives of Psychiatry 2007;19:153‐5.
TREC‐Vellore 2004 {published data only}
    1. Alexander J, Tharyan P, Adams CE, John T, Mol C, Philip J. Rapid tranquilisation of violent or agitated patients in a psychiatric emergency setting: a pragmatic randomised trial of intramuscular lorazepam versus haloperidol plus promethiazine. British Journal of Psychiatry 2004;185:63‐9. - PubMed
Wang 2004a {published data only}
    1. Wang L, Li B, Zhao Z. A controlled study of compound diazepam in adjunctive treatment for schizophrenia. Journal of Binzhou Medical College 2004;27:111‐2.
Wang 2004b {published data only}
    1. Wang G, Cai ZJ, Wang LF. A multicenter study of risperidone treatment for acute agitation in patients with schizophrenia. Chinese Journal of Psychiatry 2004;37:88‐91.
Wang 2005 {published data only}
    1. Wang DB, Xu SQ, Tang QP, Ying YF, Mei YT, He FX. Treatment of 80 cases of schizophrenia manifesting acute erethitic symptoms with quetiapine combined with clonazepam. Herald of Medicine 2005;24:687‐8.
Wang Jian 1995 {published data only}
    1. Wang J, Wang x, Chen H. Clinical controlled study of perphenazine combined with alprazolam in treatment of negative symptoms. Chinese Journal of Pharmaco Epidemiology 1995;4:137‐9.
Weber 1983 {published data only}
    1. Weber SS, Dufresne RL, Becker RE, Mastrati P. Diazepam in tardive dyskinesia. Drug Intelligence and Clinical Pharmacy 1983;17:523‐7. - PubMed
Weckowicz 1960 {published data only}
    1. Weckowicz TE, Ward T. Clinical trial of RO 5‐0690 and chlorpromazine on disturbed chronic schizophrenic patients. Diseases of the Nervous System 1960;21:527‐8. - PubMed
Wolkowitz 1986 {published data only}
    1. 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;143:85‐7. - PubMed
Wolkowitz 1988 {published data only}
    1. Wolkowitz OM, Breier A, Doran A, Kelsoe J, et al. Alprazolam augmentation of the antipsychotic effects of fluphenazine in schizophrenic patients ‐ Preliminary results. Archives of General Psychiatry 1988;45:664‐71. - PubMed
Wu 2006 {published data only}
    1. Wu Z. [Title only available in Chinese characters]. Journal of Qiqihar Medical College 2006;27:536‐7.
Yang 2003 {published data only}
    1. Yang X, Wang Z, Ling Z, et al. A randomly controlled comparison of risperidone added with intramuscular clonazepam in the treatment of excitement of schizophrenia. Shanghai Archives of Psychiatry 2003;15:98‐104.
Yu 2006 {published data only}
    1. Yu J. [Title only available in Chinese characters]. Nervous Diseases and Mental Hygiene 2006;6:129‐30.
Zhang 2007 {published data only}
    1. Zhang HS. Study of olanzapine combined with clonazepam in treatment of schizophrenia with acute psychomotor excitation. Linchuang Jingshen Yixue Zazhi 2007;17:239‐40.
Zhang YingHui 2008 {published data only}
    1. Zhang YingHui. [Title only available in Chinese characters]. Shandong Archives of Psychiatry 2008;21:59‐60.

References to studies awaiting assessment

Davis 2008 {published data only}
    1. Davis JM, Wang B, He Y, Jin H, Hu Q, Zhang M. The emergency treatment of acutely agitated psychotic schizophrenia patient. International Journal of Neuropsychopharmacology 2008;11(Suppl 1):163.
Maculans 1964 {published data only}
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Salzman 1991 {published data only}
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