Severity of depression and benzodiazepine comedication in relationship to efficacy of antidepressants in acute trials. A meta‐analysis of moclobemide trials

Abstract The severity of depression at baseline, measured by the 17‐item Hamilton rating scale for depression (HAM‐D), was analysed as a predictor of the response to treatment, with response being defined as a 50 per cent improvement on the HAM‐D or a good/very good outcome on the clinical global assessment over four weeks treatment. There is a good correlation between the two outcome measures ( r = 0.67), but the question of the optimal outcome measure in very mild depression remains unsolved. The meta‐analysis was based on 2684 patients from a data pool of double‐blind trials carried out with moclobemide compared to placebo and/or standard antidepressants. The placebo response rate was high (40 per cent) in very mild depression (HAM‐D < 16) and low (12 per cent) in moderate and severe depression. The reverse was true for moclobemide and imipramine. They showed a relatively lower response rate in cases of very mild depression but an equally good response in mild, moderate and severe depression. Co‐medication with benzodiazepines increases the response to placebo treatment and decreases the power of a comparative trial considerably. Benzodiazepines were more frequently given to patients who had been pretreated with an antidepressant before entering an experimental trial. When analysing the outcome of antidepressant drug trials, it is recommended that investigators take into account pretreatment, co‐medication and baseline severity.