Antipsychotic drugs are the primary method of treatment for people suffering from mental illness. However, many people with mental health problems do not respond well to antipsychotics which often are very good at treating positive symptoms (e.g. hearing voices or seeing things), but not so good for negative symptoms (e.g. loss of emotions, inactivity). In addition, antipsychotics can sometimes cause debilitating side effects such as movement disorders, weight gain, sleepiness and dizziness. If someone does not respond well to traditional antipsychotic drugs, psychiatrists are faced with the choice of switching to a different type of drug that may work better on its own; or adding a new drug or drugs to supplement the original antipsychotic drug treatment.
Benzodiazepines can be taken alone or in combination with more traditional antipsychotic drugs. They cause sedation, calmness and relax the muscles, so are helpful in calming down agitated people with anxiety, sleep problems, seizures, alcohol withdrawal and acute mental health problems.
This review found 34 studies with 2657 people. It compared benzodiazepines when used alone as the only medication or when used in combination with another drug for people with schizophrenia. Information from the 34 studies was generally poor, incomplete and badly reported. The 34 studies were of short duration and were small in size. The review suggests that there is little evidence to support the use of benzodiazepines either alone or in combination. However, benzodiazepines do have sedative properties that can calm people down and help them become less agitated for short periods of time. More research, particularly involving benzodiazepines as add-on treatment used in combination with traditional antipsychotic drugs, is required.
This plain language summary has been written by Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness, Email: ben.gray@rethink.org.
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.
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.
To determine the efficacy, acceptability, and tolerability of benzodiazepines in people with schizophrenia and schizophrenia-like psychoses.
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.
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.
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.
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).