The dietary supplement citicoline shows promise in the treatment of cocaine dependence in patients with bipolar disorder (BD), but its benefits appear to decline over time, new research suggests.

The results of a 12-week randomized controlled trial comparing citicoline to placebo for patients with both cocaine dependence and BD showed that the supplement significantly reduces cocaine use in the initial weeks of treatment.

“Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit,” the investigators, led by E. Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center, in Dallas, write.

The findings were published online May 22 in the American Journal of Psychiatry.

Challenging Population

“Bipolar disorder has the highest rates of substance abuse of any axis I disorder, with lifetime prevalence reaching 61%. And very little is known about treatment of substance abuse with this condition,” Dr Brown told Medscape Medical News.

A naturally occurring compound in the brain that acts through several neurotransmitter systems, citicoline was previously shown in a smaller 2007 clinical trial, conducted by the same research group, to prevent relapse in BD patients with cocaine dependence.

The investigators note that substance use in BD has several deleterious effects. Studies report higher rates of violence and aggression, higher rates of hospitalization, lower rates of recovery, and greater rates of medication nonadherence.

“Thus, patients with bipolar disorder and substance dependence are a large and challenging population and an important public health concern,” they write.

To confirm the findings of their previous study, the investigators recruited 130 outpatients with BD and cocaine dependence who were then randomly assigned to receive citicoline or placebo.

Cocaine use was measured by thrice-weekly urine drug screens during the course of the 12-week trial. As a measure of conservatism, the protocol called for all missing urine screens to be automatically classified as a positive urine test result.

The citicoline group showed an almost immediate reduction in cocaine use. Nearly 80% of the placebo group had a positive drug screen in the first 2 weeks of the trial, compared with 65% in the citicoline group.

Nevertheless, cocaine use in the citicoline group gradually increased during the course of the trial. By week 12, cocaine-positive urine screens were found in 74% of the citicoline group vs 78% of the placebo group. Still, the results were statistically significant for a reduction in cocaine use.