A meta-analysis of randomized, controlled trials comparing the use of benzodiazepines alone or in combination with antipsychotic or antihistamine medications in patients experiencing acute psychotic illness with agitated or violent behavior found no evidence to support the use of benzodiazepines in these patients.

The study, published in Cochrane Database of Systematic Reviews, used the Cochrane Schizophrenia Group’s register to employ a fixed-effect model to estimate risk ratios. Twenty trials with 695 participants were included in the analysis. Researchers noted that most of the evidence was either of low or very low quality.

One trial compared benzodiazepines with placebo and found no difference in the number of patients sedated at 24 hours. However, more placebo-treated individuals showed no improvement within the first 48 hours (relative risk [RR]: 0.62; 95% CI, 0.40-0.97).

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When benzodiazepines were compared with haloperidol, no effect for sedation was observed by 16 hours (RR: 1.3; 95% CI, 0.83-1.54) and there was no difference in the number of participants who had not improved in the medium term (RR: 0.89; 95% CI, 0.71-1.11). A small study found that those receiving olanzapine were more likely to experience improvement than those receiving benzodiazepines (RR: 1.84; 95% CI, 1.06-3.18). However, those receiving benzodiazepines were less likely to experience extrapyramidal effects (RR: 0.13; 95% CI, 0.04-0.41).

When comparing benzodiazepines with combined antipsychotic and antihistamine medications, the risk for no improvement was higher in those receiving benzodiazepines (RR: 2.17; 95% CI, 1.16-4.05). However, lorazepam had a lower risk for sedation than combined antipsychotic/antihistamine medications, whereas midazolam led to a higher risk for sedation (RR: 0.91 and 1.13; 95% CI, 0.84-0.98 and 1.04-1.23, respectively).

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When benzodiazepines plus antipsychotics were compared with benzodiazepines alone, no clear differences were found for improvement, but those receiving the combination therapy were more likely to experience sedation (RR: 1.75; 95% CI, 1.14-2.67). Results from a trial comparing benzodiazepines/antipsychotics with antihistamines/antipsychotics showed a higher risk for no clinical improvement (RR: 25.00; 95% CI, 1.55-403.99) and sedation (RR: 12.00; 95% CI, 1.66-86.59) for those receiving the combination of benzodiazepines/antipsychotics.

The authors concluded that in patients experiencing psychosis-induced aggression or agitation, adding a benzodiazepine to other drugs does not seem to provide a clear benefit and has the potential to cause unnecessary adverse effects. Furthermore, use of older antipsychotic medications unaccompanied by anticholinergic drugs does not appear justifiable. However, much higher quality research is needed in this area.


Zaman H, Sampson SJ, Beck ALS, et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev. 2017;12:CD003079.