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Lamotrigine and Lithium Appear Effective as Maintenance Therapy for Early Bipolar Disorder

Both lamotrigine and lithium monotherapies effectively delay mood episodes in patients with early bipolar disorder, according to a placebo controlled, multicentre study. Furthermore, data suggest that lamotrigine is more effective at preventing depression and lithium is more effective at preventing manic symptoms.

Few randomised, placebo-controlled, blinded studies have evaluated maintenance therapy in patients with bipolar disorder. Furthermore, no studies have analysed treatment outcomes in these patients after a recent depressive episode.

Joseph R. Calabrese, MD, at the University Hospitals of Cleveland/Case Western Reserve School of Medicine, Ohio, and colleagues therefore evaluated the efficacy and safety of lamotrigine and lithium in patients with bipolar disorder who experienced a recent depressive episode.

The study included 463 patients with bipolar I disorder and current depressive symptoms. All patients had achieved a stable dose of lamotrigine during an 8-16 week open-label phase. Patients gradually discontinued use of concomitant medications and were then randomised to receive lamotrigine (50, 200, or 400 mg/day), lithium (0.8-1.1 mEq/L), or placebo monotherapy for up to 18 months in the double blind-phase of the study.

Lamotrigine and lithium were more effective at delaying intervention for a mood episode than placebo, and both treatments showed similar efficacy. Specifically, median survival times were 200, 170, and 93 days, respectively.

Additional interventions included antidepressants, antipsychotics, lamotrigine, and benzodiazepines. Moreover, patients required intervention for depression 3 times more frequently than for mania.

Lamotrigine was more effective than placebo at delaying intervention for depression with 57% of lamotrigine-treated patients being intervention-free for depression at 1 year. Notably, the efficacy of lithium on depression did not differ significantly from lamotrigine or placebo.

In contrast, lithium was more effective than placebo at delaying intervention for manic symptoms, while lamotrigine had similar efficacy as placebo and lithium.

The superiority of each treatment over placebo was also evident in measures of symptom severity and overall function.

Rash was the only adverse event reported more frequently in patients taking lamotrigine. Furthermore, somnolence and tremor were more commonly reported in patients taking lithium.

The authors conclude that "in this large, randomised, 18-month study, lamotrigine and lithium were effective maintenance treatments for bipolar disorder." They further add that "lamotrigine [was] primarily effective in preventing depressive episodes and lithium [was] primarily effective in preventing manic episodes."

J Clin Psychiatry 2003 Sep;64:9:1013-24. "A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder"

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