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Spotlight on Lamotrigine in Bipolar Disorder

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Lamotrigine (Lamictal®), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane.

Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months’ duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure.

Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania.

Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine- than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment 1 This Spotlight is derived from abstract and summary text of an Adis Drug Evaluation originally published in full in Drugs 2003; 63 (19): 2029-2050. Reviewers of the original full text article are listed in the Acknowledgements section. was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain.

The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine.

Conclusion: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.

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The full text article in Drugs 2003; 63 (19): 2029-50 was reviewed by: M. Berk, Department of Psychiatry, University of Melbourne, Geelong, Victoria, Australia; C.L. Bowden, Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas, USA; J.R. Calabrese, Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; R.T. Joffe, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA; T.A. Ketter, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA; P.B. Mitchell, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

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Correspondence to David R. Goldsmith.

Additional information

This Spotlight is derived from abstract and summary text of an Adis Drug Evaluation originally published in full in Drugs 2003; 63 (19): 2029–2050. Reviewers of the original full text article are listed in the Acknowledgements section.

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Goldsmith, D.R., Wagstaff, A.J., Ibbotson, T. et al. Spotlight on Lamotrigine in Bipolar Disorder. CNS Drugs 18, 63–67 (2004).

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  • Bipolar Disorder
  • Lamotrigine
  • Bipolar Depression
  • Bodyweight Gain
  • Valproate Semisodium