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

Abstract

Background: 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 the 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 licencing status. Aims: To review the evidence for the efficacy and safety of LTG in the treatment of all phases of BD. Methods: PubMed was searched for double-blind, randomised, placebo-controlled trials using the keywords: LTG, 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. Conclusion: 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.

Diagnosis and Treatment of Bipolar Disorder

“…People of childbearing age using valproate or carbamazepine should be instructed about these risks and contraceptive strategies must be implemented. Lamotrigine might be a safer option, with a risk of malformation estimated at 2% to 3%, but not much data are available …”

New treatment strategies for bipolar disorder in the elderly

“…Some studies suggest efficacy in acute bipolar depression, but the results are inconsistent. There is little evidence to support its efficacy in acute mania, unipolar depression or rapidly recurrent bipolar disorder, and therefore it has a somewhat limited spectrum of action [19]. In various studies, lamotrigine shortened the time to relapse of a depressive episode [7].…”

The growth and development outcomes of foetuses born of albino rats (Rattus Norvegicus) prenatally exposed to varying doses of lamotrigine

“…The safety of embryos and foetuses upon prenatal administration of lamotrigine at different doses and during varied trimesters is not well elucidated (Etemad et al, 2012). Though the efficacy and safety of lamotrigine on foetal growth and development have been demonstrated in some past study results, (Besag et al, 2021, Diav-Citrin et al, 2017 others have associated its use with adverse teratogenic effects similar to those of older-generation anticonvulsants (Vajda et al, 2013, Sabers et al, 2004. Further, some other past results are as well not conclusive, advocating for further studies to be carried out (Tennis et al, 2002, Cunnington et al, 2005.…”