Lamotrigine for treatment of bipolar depression

independent meta-analysis and meta-regression of individual patient data from five randomised trials

Geddes, John R. MD FRCPsych
Goodwin, Guy M. DPhil, FMedSci
Calabrese, Joseph R. MD

John R. Geddes, MD FRCPsych, Department of Psychiatry, University of Oxford, UK; Joseph R. Calabrese, MD, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio, USA; Guy M. Goodwin, DPhil, FMedSci, Department of Psychiatry, University of Oxford, UK

Correspondence: John R. Geddes, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK. Email: [email protected]

Declaration of interest

J.R.C. is a member of the psychiatry advisory board for GlaxoSmithKline. J.R.G. is Chief Investigator and G.M.G. is a co-investigator on the independent Medical Research Council-funded trial: Comparative Evaluation of QUEtiapine-Lamotrigine combination v. quetiapine monotherapy (and folic acid v. placebo) in people with bipolar depression (CEQUEL).

(First received 3 December 2007, final revision 30 May 2008, accepted 18 June 2008)

British Journal of Psychiatry 194(1):p 4-9, January 2009.

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–Åsberg 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.