Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials

Background: Psychostimulants have been used in the treatment of depression, with mixed results. This metaanalysis examines the efficacy and tolerability of the stimulant Lisdexamfetamine (LDX) as an add-on strategy in those with MDD who have failed to respond to an antidepressant. Method: Randomized control trials were identified and extracted from Pubmed; Web of Science; PsychINFO; and Cochrane Library. The efficacy of LDX was evaluated using Hedges' g and Odds Ratio, whereas Risk Difference was used to assess the safety and tolerability of LDX. Results: Four studies met inclusion criteria. LDX did not demonstrate superiority in efficacy relative to placebo as indicated by a Hedges' g score of 0.126 (95% CI -0.040-0.291; p = 0.136) for mean change in Montgomery-Asberg Depression Rating Scale. Odds ratios of 1.206 (95% CI 0.745-1.954; p = 0.446) and 1.244 (95% CI 0.959-1.614; p = 0.1) were found for remission and response rates respectively. Risk differences of -0.1 (95% CI -0.155-(-0.045); p < 0.001) indicated a 10% increase chance of developing treatment-emergent adverse events (TEAE) in the LDX group. There was no significant difference in risk for developing serious or severe TEAE and discontinuing treatment due to TEAE. Limitations: The number of included studies was small and only one metric was available for analysis of antidepressant efficacy of LDX. Conclusions: LDX when used as antidepressant augmentation produced a small effect in improving depressive symptoms that approached trend-level significance and demonstrated comparable tolerability to placebo. Further studies are needed to determine the optimal clinical subset of depressive symptoms responsive to LDX augmentation.