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Charles L. Bowden, MD; Joseph R. Calabrese, MD; Gary Sachs, MD; Lakshmi N. Yatham, MB, FRCPC, MRCPsych; Shaheen Akthar Asghar, MD; Magne Hompland, MD; Paul Montgomery, PharmD; Nancy Earl, MD; Tonya M. Smoot, MS; Joseph DeVeaugh-Geiss, MD; for the Lamictal 606 Study Group

Arch Gen Psychiatry. 2003;60:392-400.

Background  Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder.

Methods  After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo as double-blind maintenance treatment for as long as 18 months.

Results  Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double-blind maintenance treatment (lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode (lamotrigine vs placebo, P = .02; lithium vs placebo, P = .006). Lamotrigine was superior to placebo at prolonging the time to a depressive episode (P = .02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic, or mixed episode (P =.006). The most common adverse event reported for lamotrigine was headache.

Conclusions  Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode. The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression.

From the Departments of Psychiatry and Pharmacology, University of Texas Health Science Center at San Antonio (Dr Bowden); the Department of Psychiatry, University Hospitals of Cleveland–Case Western Reserve School of Medicine, Cleveland, Ohio (Dr Calabrese); the Department of Psychiatry, Massachusetts General Hospital, Boston (Dr Sachs); the Department of Psychiatry, University of British Columbia, Vancouver (Dr Yatham); Ullevål University Hospital, Oslo, Norway (Dr Asghar); Affective Disorders Clinic, Bergen, Norway (Dr Hompland); and Research and Development, GlaxoSmithKline, Research Triangle Park, NC (Drs Montgomery, Earl, and DeVeaugh-Geiss and Ms Smoot).

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