Effect of Lamotrigine on Cognitive Complaints in Patients With Bipolar I Disorder

Arifulla Khan, M.D.; Lawrence D. Ginsberg, M.D.; Gregory M. Asnis, M.D.; Frederick K. Goodwin, M.D.; Kimberly H. Davis, M.S.; Anupama A. Krishnan, M.S.; and Bryan E. Adams, Ph.D.

Background: This analysis describes the effects of bipolar I disorder on self-reported neurocognitive measures and remediation of these deficits with lamotrigine therapy.

Method: Data were derived from 2 clinical trials designed to assess the efficacy of lamotrigine as maintenance therapy for recently manic (N = 349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week open stabilization phase, patients received lamotrigine as monotherapy or as adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to measure cognitive functioning at baseline and at the end of the open-label phase. To examine the relationship between depressive and manic symptomatology, initiation of lamotrigine, and cognitive functioning, correlational analyses and analyses of covariance were conducted.

Results: Bipolar patients in both trials had significant cognitive impairment; however, it was much greater in index episode depressed bipolar patients compared with index episode manic patients. In both studies, substitution of lamotrigine for other psychotropic medications significantly improved the mean scores from baseline to the end of the open-label phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or 35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062) showed similar improvement. Cognitive impairment was significantly correlated with depression symptom severity based on Hamilton Rating Scale for Depression scores (p < .0001). After controlling for change in mood, age, gender, baseline score, duration of illness, and duration of use of other psychotropics, a significant improvement in cognition was observed during the open-label phase when lamotrigine was used as monotherapy/adjunctive therapy.

Conclusion: Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity.

(J Clin Psychiatry 2004;65:1483-1490)

Received March 26, 2003; accepted Aug. 12, 2004. From the Northwest Clinical Research Center, Bellevue, Wash. (Dr. Khan); Red Oak Psychiatry Associates, Houston, Tex. (Dr. Ginsberg); Montefiore Medical Center Anxiety and Depression Clinic, Bronx, N.Y. (Dr. Asnis); Center on Neuroscience, Medical Progress, and Society and George Washington University Medical Center, Washington, D.C. (Dr. Goodwin); RTI Health Solutions, Research Triangle Park, N.C. (Ms. Davis); GlaxoSmithKline, Research Triangle Park, N.C. (Ms. Krishnan); and Clinforce, Inc., Research Triangle Park, N.C. (Dr. Adams).

GlaxoSmithKline (Research Triangle Park, N.C.), maker of Lamictal (lamotrigine), supported the research described in this article.

Financial disclosure is listed at the end of the article.

Corresponding author and reprints: Arifulla Khan, M.D., Northwest Clinical Research Center, 1900 116th Ave., NE Suite 112, Bellevue, WA 98004 (e-mail: akhan@nwcrc.net).