title: Efficacy and safety of antidepressant augmentation with lamotrigine in patients with treatment-resistant depression: a randomized, placebo-controlled, double-blind study.
abstract: 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.
  
  
  METHODS
  A double-blind pilot study was conducted between March 2004 and January 2006 with 34 nonbi-polar, nonpsychotic patients who had DSM-IV major depressive disorder and were resistant to at least 2 anti-depressants. 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 anti-depressants. 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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00652171.
authors.affiliation: Mental Health Service of the City Hall of Belo Horizonte, Minas Gerais, Brazil. milena73@yahoo.com
authors.forename: Milena Antunes
authors.initials: MA
authors.lastname: Santos
authors.forename: Fábio Lopes
authors.initials: FL
authors.lastname: Rocha
authors.forename: Cláudia
authors.initials: C
authors.lastname: Hara