Efficacy and tolerability of pharmacological and non-pharmacological interventions in older patients with major depressive disorder: A systematic review, pairwise and network meta-analysis.

As there is currently no comprehensive evaluation about the efficacy and safety of interventions in elderly patients with major depressive disorder, we did a systematic review and network meta-analysis about all interventions in this population. We searched the specialised register of the Cochrane common mental disorders group, MEDLINE, EMBASE, PsycINFO, CochraneLibrary, ClinicalTrials.gov and the WHO registry until Dec 12, 2017 to identify all randomized controlled trials about the treatment of major depressive disorder in patients over an age of 65. The primary outcome was response defined as reduction of at least 50% on the Hamilton Depression Scale or any other validated depression scale. Secondary outcomes were remission, depressive symptoms, dropouts total, dropouts owing to inefficacy and dropouts due to adverse events, quality of life and social functioning. Additionally, we analysed 116 adverse events. We identified 129 references from 53 RCTs with 9274 participants published from 1990 to 2017. The mean participant age was 73.7 years. In terms of the primary outcome response to treatment the network-meta-analysis showed significant superiority compared to placebo for quetiapine and duloxetine; in addition, agomelatine, imipramine and vortioxetine outperformed placebo in pairwise meta-analyses, and there were also significant superiorities of several antidepressants compared to placebo in secondary efficacy outcomes. Very limited evidence suggests that competitive memory training, geriatric home treatment group and detached mindfulness condition reduce depressive symptoms. Several antidepressants and quetiapine have been shown to be efficacious in elderly patients with major depressive disorder, but due to the comparably few available data, the results are not robust. Differences in the multiple side-effects analysed should also be considered in drug choice. Although there were significant effects for some non-pharmacological treatments, the overall evidence for non-pharmacological treatments in major depressive disorder is insufficient, because it is based on a few trials with usually small sample sizes.