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

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

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.

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.

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.