Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials

Background There is uncertainty about the efficacy of lamotrigine in bipolar depressive episodes. Aims To synthesise the evidence for the efficacy of lamotrigine in bipolar depressive episodes. Method Systematic review and meta-analysis of individual patient data from randomised controlled trials comparing lamotrigine with placebo. Results individual data from 1072 participants from five randomised controlled trials were obtained. More individuals treated with lamotrigine than placebo responded to treatment on both the Hamilton Rating Scale for Depression (HRSD) (relative risk (RR)=1.27, 95% CI 1.09-1.47, P=0.002) and Montgomery-Asberg Depression Rating Scale (MADRS) (RR=1.22, 95% CI 1.06-1.41, P=0.005). There was an interaction (P=0.04) by baseline severity of depression: lamotrigine was superior to placebo in people with HRSD score >24 (RR=1.47, 95% CI 1.16-1.87, P=0.001) but not in people with HRSD score <= 24 (RR=1.07, 95% CI 0.90-1.27, P=0.445). Conclusions There is consistent evidence that lamotrigine has a beneficial effect on depressive symptoms in the depressed phase of bipolar disorder. The overall pool effect was modest, although the advantage over placebo was larger in more severely depressed participants.