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A Trial of Lamotrigine for Cocaine Dependence in Bipolar Disorder

In Session With E. Sherwood Brown, MD, PhD:

A Trial of Lamotrigine for Cocaine Dependence in Bipolar Disorder


August 6, 2012

E. Sherwood Brown, MD, PhD


Professor of Psychiatry; Director, Psychoneuroendocrine Research Program, University of Texas Southwestern Medical Center, Dallas, TX


First published in Psychiatry Weekly, Volume 7, Issue 15, on August 6, 2012


Q: To what extent did lamotrigine influence cocaine dependence in patients with bipolar disorder?

A: Bipolar disorder (BD) seems to have the highest rates of substance abuse and dependence of any Axis I psychiatric disorder, with a 61% prevalence rate for BD I disorder and 48% for BD II disorder. Stimulant use and dependence—cocaine in particular—are common among BD patients.

In 2003 we conducted an open-label uncontrolled trial of lamotrigine in BD with comorbid cocaine dependence, with promising results. We attempted to replicate those findings recently with a larger placebo-controlled trial of lamotrigine in BD with comorbid cocaine dependence. This study is, to my knowledge, the largest of the very few studies conducted in BD and cocaine dependence, and one of very few placebo-controlled trials in this area.

Subjects (n=120) received lamotrigine or placebo for 10 weeks. The lamotrigine group had an average age of 45.1 years vs 43.5 years in the placebo group, and women composed approximately 40% of both groups. Lamotrigine was titrated slowly to minimize side effects. Urine drug screening was the primary outcome measure, with other assessments including self-reported drug craving and mood ratings scales.

The most remarkable finding from this study was a reduction in self-reported cocaine use. The lamotrigine group reported significantly fewer dollars per week spent on cocaine than placebo. We unfortunately did not see the same finding on the more objective measure of urine drug screen.

We obtained urine drug screens only once a week, limiting the study’s power and the amount of urine drug screen data for analysis. Our findings do suggest, however, that if subjects did not actually use cocaine less frequently they may have used a smaller amount of cocaine. We didn’t see a strong effect on the number of self-reported days of cocaine use, either, so it could be that lamotrigine is simply decreasing the amount they use in a day or at a time. If subjects used much less cocaine twice a week, for example, we could detect that on the self-reported amount used, but urine drug screens would still test positive for cocaine.

Q: Were these subjects enrolled in any concomitant psychotherapy treatment?

A: Not in this study. It wasn’t part of the protocol. They did come in and see a doctor at each visit, but there wasn’t a formal psychotherapy as part of the study. Cocaine clinical trials generally include a psychotherapeutic component. In terms of a trial design, psychotherapy could have an additive effect on decreasing cocaine use and keeping patients in treatment longer. A potential downside of including psychotherapy in such a trial is that if it did have a larger effect it might make it more difficult to detect a medication vs. placebo difference. We often observe a fairly large initial reduction in medication and placebo groups, which is probably related to nonspecific effects of being in a research study. Adding a psychotherapy group would make it even more difficult to see a difference between both groups.


Disclosure: This research was supported by the Stanley Medical Research Institute. Medication for this study was provided by GlaxoSmithKline.


1. Brown ES, Sunderajan P, Hu LT, Sowell SM, Carmody TJ. A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence. Neuropsychopharmacology. 2012 Jun 6. [Epub ahead of print]