Efficacy and Safety of Antidepressant Augmentation With Lamotrigine in Patients With Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Double-Blind Study

Objective: This study reports a clinical trial evaluating lamotrigine safety and efficacy as an antidepressant augmentation agent in treatment-resistant depression, therefore adding more empirical evidence to the limited number of studies on the use of lamotrigine.

Method: A double-blind pilot study was conducted between March 2004 and January 2006 with 34 nonbipolar, nonpsychotic patients who had DSM-IV major depressive disorder and were resistant to at least 2 antidepressants. The subjects were taking antidepressant therapy and were randomly assigned to receive placebo or lamotrigine as an adjunct therapy for 8 weeks. They were evaluated on a biweekly basis in order to assess the efficacy and the safety of the drug. Efficacy was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impressions (CGI) scale. Response was defined as a decrease of at least 50% from baseline on the MADRS and a final score <= 2 on the CGI. Safety was assessed by keeping record of treatment-emergent adverse events.

Results: The results of the adjunct treatment with lamotrigine did not reveal a significant difference according to the MADRS (p = .45). No differences between the 2 treatment groups were revealed by the repeated-measures analysis of variance or by the analysis based on the CGI (p = .45). More than 50% of the patients had been treated with at least 3 different antidepressants. The most frequent adverse events were nausea, rash, and dyspepsia in the lamotrigine group and dizziness and headache in the placebo group.

Conclusions: In this study, although it was safe, lamotrigine was not found to be an efficient augmentation agent in treatment-resistant depression. Small sample size, higher chronicity, and refractoriness may be related to treatment failure.