Trials that assessed the effectiveness of lamotrigine in adults (aged 18 to 65 years) diagnosed with a major depressive disorder were eligible for inclusion. In eligible trials, lamotrigine had to be given at minimum doses of 50 mg daily for four weeks. Eligible patients were required to have previously received at least one anti-depressant, at recognised therapeutic doses, for a minimum of four weeks. Patients with bipolar I depression, previous prescription of lithium, co-morbid schizophrenia or drug and alcohol dependence were excluded.
The primary outcomes were response and remission rates. Outcomes measures were quantified in scores on the Hamilton Depression rating scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI) scale and the Global Assessment of Functioning (GAF) scale.
The patients in the included randomised controlled trial (RCT) began treatment with a fixed dose of fluoxetine of 20mg/day and were assigned to receive either lamotrigine or placebo. The commencing dose of lamotrigine was 25mg/day for two weeks, which was increased to 50mg/day for two weeks and to a maximum dose of 100mg/day thereafter. The patients enrolled also had co-morbid personality disorders, borderline personality disorder and anti-social personality disorder.
Other included studies compared lamotrigine with lithium, or lamotrigine as augmentation to venlafaxine, mirtazepine or sertraline or other drug therapy.
Three reviewers independently performed the study selection.