Meta-Analysis of Antidepressant Augmentation: Piling on in the Absence of Evidence

Background: Treatment of depression with a single pharmaceutical agent often does not work, and several agents may be tried or combined to increase efficacy. Augmentation involves the addition of one or more medications to an existing antidepressant monotherapy to enhance mood and overall antidepressant response. Approximately 22% of individuals with unipolar depression are prescribed augmentation strategies. This study examined the effectiveness of augmentation strategies. Methods: A Medline search of studies published before January 1, 2007 was conducted to assess the extent of published data on the most frequently prescribed augmentation strategies. Studies with completed original data, sufficient efficacy data, and participants diagnosed with unipolar depression were included. Letters to the editor, preliminary data, data only presented at conferences, and small uncontrolled case reports were excluded. Results: 13 studies contained sufficient data to calculate an effect size. Mean estimated effect size of all 13 studies calculated with random effects was 0.1782 with a 95% confidence interval of −0.2513−0.6076. Conclusions: There are minimal published data examining antidepressant augmentation, and augmentation is a minimally effective treatment option.