The effectiveness of off-label dopamine stimulating agents in depressive disorder: A systematic review and meta-analysis

The chronicity of depressive disorders is a major problem. Dopamine stimulating agents (DSA) are suggested to hold a promising potential in depression management, particularly in older adults, in whom dopamine deficiency due to aging may be an underlying cause. More evidence is needed to support these drugs in the management of depression. Therefore, we conducted a systematic literature review and meta-analysis. Data was extracted from eighteen randomized-controlled-trials and eight open-label-studies. Additional meta-regression-analyses were performed to examine superiority of monotherapy versus augmentation, and to rule out a putative age effect. DSA were found to reduce depressive symptoms (SMD=-0.26, 95%CI(-0.43;-0.10]). Heterogeneity was high and a significant Egger's test indicated publication bias. Adjustment for missing studies, using trim-and-fill-methodology, reduced the effect size (SMD=-0.17, 95%CI(-0.39;0.05]), which lost statistical significance. Removing the outlier study from the analysis, the effect size remained marginally small, but was statistically-significant (SMD=-0.17, 95%CI(-0.31;-0.02]). Neither augmentation nor monotherapy was superior. No age effect was found. It can be concluded that off-label DSA are overall effective in reducing depressive symptoms. However, the evidence is weak, regarding the publication bias, and modest-to-weak treatment effects. Well-designed high-quality trials are highly needed, before dopamine stimulating agents can be adequately posi-tioned in future depression treatment protocols.