Clonazepam and lorazepam in acute mania: a Bayesian meta-analysis

Abstract 

Background: Clonazepam and lorazepam are used in the treatment of acute mania but trial results are conflicting. Methods: Studies were identified by searching MEDLINE and EMBASE for lorazepam or clonazepam in acute mania between 1966 and 2000. Seven randomized controlled trials were found comparing clonazepam or lorazepam to placebo, haloperidol or lithium in acute mania. Data on 206 patients were analyzed. Results: The heterogeneity of trial designs and the use of different comparators necessitated a Bayesian hierarchical meta-analysis with three models: (a) random trial effect and fixed treatment effects, (b) random trial and treatment effects, (c) random trial and treatment effects with trial variance unknown. With all models, clonazepam decreased psychopathology scores statistically significantly with the following standardized responses: model (a): 1.26 (95% predictive interval (PI) 0.33 to 2.28), model (b): 1.21 (95% PI 0.08 to 2.53), model (c): 1.41 (95% PI 0.12 to 2.67). Lorazepam did not yield statistically significant standardized responses for any of the three models: model (a): 0.79 (95% PI −0.29 to 1.89), model (b): 0.77 (95% PI −0.57 to 2.24) and model (c): 0.74 (−0.82 to 2.20). Haloperidol yielded statistically significant standardized responses in the three models but lithium effect was statistically significant only in model (a). Safety data were in line with the usual safety profile of benzodiazepines. Limitations: Trial designs were heterogenous and patient number was limited. Conclusions: This meta-analysis suggests that clonazepam is efficient and safe in the treatment of acute mania, but the results remain inconclusive for lorazepam.

Keywords:  Clonazepam, Lorazepam, Acute mania, Bayesian meta-analysis