Systematic review of lamotrigine augmentation of treatment resistant unipolar depression (TRD).

Objective: Our aim was to review all the evidence of lamotrigine's effectiveness in treatment resistant depression after at least one failed antidepressant trial.

Method: We used a systematic search strategy to identify studies that included adults aged 18-65 years with a diagnosis of unipolar depression who had not responded to at least a 4-week course of a recommended dose of an antidepressant.

Results: We found only one randomized, double blind study that has been published, showing its effectiveness for treatment-resistant depression. In this study, lamotrigine was found statistically superior to placebo on the CGI scale for severity and improvement; however, it was not on the HAM-D (primary end point) and MADRS scales. There were a number of smaller non RCT's which are included.

Conclusions: There is little evidence to guide the use of lamotrigine for depression that has not responded to a course of antidepressants. Treatment-refractory depression continues to be significant mental health problem and large RCT trials are needed to inform clinical practice.