Lamotrigine Is Helpful in Preventing Depressive Relapses in Bipolar Disorder

Laurie Barclay, MD

February 18, 2004

Feb. 18, 2004 — Lamotrigine (LTG) is better than placebo or lithium for preventing depressive relapses in bipolar disorder, according to a presentation at the International Congress of Biological Psychiatry held in Sydney, Australia, from Feb. 9-13.

"The results of this study suggest that [LTG] is the only medication that has better efficacy in preventing depressive relapse," lead author Lakshmi N. Yatham, MBBS, FRCPC, MRCPsych, told Medscape. Dr. Yatham is a professor of psychiatry and Michael Smith Foundation Senior Scholar at the University of British Columbia in Vancouver, Canada. "This has important clinical implications, as all medications currently used for prophylaxis of bipolar disorder have better effiacy in preventing mania than depression."

Lithium, which is commonly used to treat bipolar mania, is also thought to have antidepressant activity. Based on the results of two clinical trials in bipolar I disorder that enrolled 463 currently or recently depressed patients and 175 currently or recently manic patients, the investigators compared the effects of 18 months of prophylactic treatment with placebo (PBO), lithium (Li), and LTG.

Compared with placebo, LTG treatment resulted in fewer recently manic patients who required intervention for depression (LTG 14%, Li 22%, PBO 30%; P = .034 for LTG vs. PBO); reported depressive adverse events (LTG 0, Li 4%, PBO 3%); met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for depression (LTG 10%, Li 17%, PBO 28%; P = .024 for LTG vs. PBO), or had Hamilton Depression Rating Scale (HAMD) scores greater than 20 (LTG 3%, Li 11%, PBO 19%; P = .011 for LTG vs. PBO).

In recently depressed patients, the treatment groups did not differ significantly in the incidence of depressive symptoms. Intervention for depression was required in 39% of the PBO group, 34% of the LTG group, and 38% of the Li group. The corresponding proportions for reported depressive adverse events were 2%, 4%, and 3%; for DSM-IV depression, the proportions were 36%, 31%, and 36%; and for HAMD scores greater than 20 were 26%, 22%, and 18%, respectively.

The authors suggest that because LTG can protect against depressive symptoms in currently or recently manic patients, administration of LTG should be considered during or shortly after stabilization of mania, before depressive symptoms occur.

"Clinicians can combine lamotrigine with lithium or atypical antipsychotics for achieving optimal control of both depression and mania," Dr. Yatham said.

GlaxoSmithKline (GSK) supported this study. Dr. Yatham and some of the coauthors are on the advisory board and on the speakers' bureau of GSK.

ICBP 2004: Abstract 5. February 9-13, 2004.

Reviewed by Gary D. Vogin, MD

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