Hierarchical Meta-analysis Research Articles

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

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.

How stable is the risk curve between alcohol and all-cause mortality and what factors influence the shape? A precision-weighted hierarchical meta-analysis.

To determine the influence of six determining variables on the shape of the risk curve between alcohol and all-cause mortality. Based on a systematic search with clear inclusion criteria, all articles on alcohol and all-cause mortality until 2000 were included. Precision-weighted pooling of relative risks (RRs); precision-weighted hierarchical analysis. For pooling: RRs for different categories of average volume of drinking, lifetime abstainers and ex-drinkers. For hierarchical analysis: on first level: consumption in grams of pure alcohol per day; on second level: length of follow-up time in months; per capita consumption; average age, proportion of abstainers, average volume of drinking, and variability of average volume of drinking at baseline. RR of former and current drinkers for all-cause mortality compared to abstainers. The main hypotheses could be confirmed for males: Ex-drinkers had a higher mortality risk than lifetime abstainers; the higher and the more diverse the average volume of alcohol consumption, the wider the dip of the curve; the older the persons at baseline, the more pronounced the protective effect; and the longer the follow-up time, the less pronounced the protective effect. Except for average volume of drinking effects for females went in the same direction but with one exception did not reach significance. There are systematic influences on the shape of the risk curve between alcohol and all-cause mortality. The overall beneficial effect of light to moderate drinking remained under all scenarios, indicating a high validity of the overall shape despite the heterogeneity between studies.