Pirlindole in the treatment of depression: a meta-analysis

Abstract

Background: Depressive disorders are common health problems. Both preclinical and clinical studies have shown that pirlindole, a tetracyclic compound, is suitable for the management of depression; however, a systematic review is needed to accurately select randomized controlled trials (RCTs) for a meta-analysis that will provide more consistent and accurate results regarding the efficacy and tolerability of the drug.

Objectives: To evaluate the efficacy and frequency of adverse events with pirlindole in comparison with active comparators (monoamine oxidase inhibitors [MAOIs], tricyclic antidepressants, tetracyclic antidepressants, and selective serotonin reuptake inhibitors [SSRIs]) for the treatment of major depression.

Methods: Data were searched through MEDLINE (via PubMed), EMBASE, the Cochrane Central Register of Controlled Trials and a manual search through the sponsor's available archives (1966 to 30 August 2010). The meta-analysis was performed using the Mantel-Haenszel technique and analysing data through Comprehensive Meta-Analysis software version 1.0.23. Studies were included if they were RCTs evaluating the efficacy and number of reported adverse events with pirlindole in comparison with active comparators for the treatment of major depression in adults. Placebo-controlled trials were excluded to minimize study heterogeneity.

Results: This systematic review included ten published articles and one non-published report corresponding to a total of 13 clinical trials in the adult population. Two RCTs were excluded from the meta-analysis because the comparator was placebo. Two more studies were excluded, one because randomization could not be confirmed and the other because it described follow-up data on patients from a study that had already been included in the meta-analysis. Therefore, only nine RCTs were included in the meta-analysis. No differences were found between pirlindole and its active comparators with regard to the percentage of patients whose clinical condition improved by 50% according to the Hamilton Depression Rating Scale (HDRS) [odds ratio (OR) 1.52; 95% confidence interval [CI] 0.92, 2.51; p = 0.11] and Hamilton Anxiety Rating Scale (HARS) [OR 1.15; 95% CI 0.69, 1.90; p = 0.59]. With regard to the improvements in HDRS and HARS, the results were favourable for patients treated with pirlindole (depression: absolute value 0.18; 95% CI -0.01, 0.37; p = 0.06; anxiety: absolute value 0.26; 95% CI 0.03, 0.48; p = 0.03).

Conclusion: This systematic review and meta-analysis showed that all RCTs included reported efficacy outcomes for pirlindole comparable to those of its comparators, and that pirlindole was significantly better in terms of reducing anxiety symptoms. However, the analysis of these results should take into account the quality of the original included articles, which had a mean Jadad trial quality score of 3.7 (out of 5). Therefore, further clinical trials should be conducted to evaluate the benefits of pirlindole.