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Efficacy and safety of lamotrigine in the treatment of bipolar disorder across the lifespan: a systematic review

Lookup NU author(s): Dr Aditya SharmaORCiD



This is the authors' accepted manuscript of an article that has been accepted and is due to be published in its final definitive form by Sage Publications Ltd., 2021.

For re-use rights please refer to the publisher's terms and conditions.


AbstractBackground: Bipolar disorder (BD) is a cyclic mood disorder characterised by alternating episodes of mania/hypomania and depression interspersed with euthymic periods. Lamotrigine (LTG) demonstrated some mood improvement in patients treated for epilepsy, leading to clinical studies in patients with BD and its eventual introduction as maintenance therapy for prevention of depressive relapse in euthymic patients. Most current clinical guidelines include LTG as a recommended treatment option for the maintenance phase in adult BD, consistent with its global licensing status.Aims: To review the evidence for the efficacy and safety of lamotrigine in the treatment of all phases of BD.Methods: PubMed was searched for double-blind, randomised, placebo-controlled trials using the keywords: lamotrigine, Lamictal, “bipolar disorder”, “bipolar affective disorder”, “bipolar I”, “bipolar II”, cyclothymia, mania, manic, depression, depressive, “randomised controlled trial”, “randomised trial”, RCT, and “placebo-controlled”, and corresponding MeSH terms. Eligible articles published in English were reviewed.Results: Thirteen studies were identified. The strongest evidence supports utility in the prevention of recurrence and relapse, particularly depressive relapse, in stabilised patients. Some evidence suggests efficacy in acute bipolar depression, but findings are inconsistent. There is little or no strong evidence in support of efficacy in acute mania, unipolar depression, or rapid cycling BD. Few controlled trials have evaluated LTG in bipolar II or in paediatric patients. Indications for safety, tolerability, and patient acceptability are relatively favourable, provided there is slow dose escalation to reduce the probability of skin rash.Conclusions: On the balance of efficacy and tolerability, LTG might be considered a first-line drug for BD, except for acute manic episodes or where rapid symptom control is required. In terms of efficacy alone, however, the evidence favours other medications.

Publication metadata

Author(s): Besag F, Vasey MJ, Sharma AN, Lam ICH

Publication type: Article

Publication status: In Press

Journal: Therapeutic Advances in Psychopharmacology

Year: 2021

Acceptance date: 04/08/2021

Date deposited: 01/09/2021

ISSN (print): 2045-1253

ISSN (electronic): 2045-1261

Publisher: Sage Publications Ltd.