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Evidence summaries

Benzodiazepines Alone or in Combination with Antipsychotic Drugs for Acute Psychosis

Benzodiazepines may be as effective as antipsychotics for acute psychosis. Adding them to antipsychotics may not bring added benefit but may cause more adverse effects. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 21 studies with a total of 1968 subjects with acute psychotic illnesses. Participants in 9 trials were inpatients and in 11 trials they were newly admitted. In most trials the participants were of mixed diagnoses. The data up to 48 hours were included for this review.

  • Benzodiazepines vs. placebo (1 trial, n=102): there was no significant difference for most outcomes, although there was a higher risk of no improvement in people receiving placebo in the medium term (1 to 48 hours) (RR 0.62, 95% CI 0.40 to 0.97).
  • Benzodiazepines vs. antipsychotics (5 trials, n=308): There was no difference in the number of participants who had not improved in the medium term (RR 1.10, 95% CI 0.85 to 1.42). People receiving benzodiazepines were less likely to experience extrapyramidal effects (EPS) in the medium term (RR 0.15, 95% CI 0.06 to 0.39; 8 RCTs, n=536).
  • Combined benzodiazepines and antipsychotics vs. benzodiazepines alone: no significant results.
  • Combined benzodiazepines/antipsychotics (all studies compared haloperidol) vs. the same antipsychotics alone (haloperidol): there was no difference between groups in improvement in the medium term (RR 1.27, 95% CI 0.94 to 1.70; 3 RCTs, n=155). Sedation was more likely in people who received the combination therapy (RR 1.75, 95% CI 1.14 to 2.67; 3 RCTs, n=172). However, more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine (RR 25.00, 95% CI 1.55 to 403.99; 1 RCT, n=60) or ziprasidone (RR 4.00, 95% CI 1.25 to 12.75; 1 RCT, n=60). When haloperidol and midazolam were compared with olanzapine, there was some evidence the combination was superior in terms of improvement, sedation and behaviour.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and imprecise results (small trials).

    References

    • Gillies D, Sampson S, Beck A et al. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database Syst Rev 2013;4():CD003079. [PubMed]

Primary/Secondary Keywords