Fixed dose-combination products in psychiatry: Systematic review and meta-analysis

Despite highly prevalent use of drug combinations in psychiatry, combination products are not commonly available. We aimed to systematically review the evidence for the use and efficacy of combination products in the practice of psychiatry. Systematic search of major data bases yielded nine double-blind randomized controlled trials, which generated 15 comparisons of combination products against a single therapeutic agent, that included a placebo. All these studies included 2827 participants: 976 in their combination products arms and 1851 patients in the comparator arms. The number of combination products were identified, but all except two studies tested only one combination drug (e.g. olanzapine and fluoxetine (OFC)). All combined formulations were significantly superior to a single agent, with standardized mean distance (SMD) of − 0.29 (confidence interval (CI) = − 0.43, − 0 .14; p < 0.001) in improving depression. In the subgroup analysis, the OFC combination was significantly superior to a single therapeutic agent for bipolar depression (SMD = − 0.32; CI = − 0.45, − 0.19; p < 0.001) and for treatment-resistant depression (SMD = − 0.29; CI = − 0.49, − 0.08; p < 0.005), but not for borderline personality nor major depressive disorder (MDD). The evidence in general medicine suggests that combination products can offer significant advantage in improving efficacy and treatment adherence; but in psychiatry, research and development in fixed-dose combinations has been limited.