Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

A Randomized, Placebo-Controlled Trial of Citicoline Add-On Therapy in Outpatients With Bipolar Disorder and Cocaine Dependence

Brown, E. Sherwood MD, PhD*; Gorman, April R. MS; Hynan, Linda S. PhD*†

Journal of Clinical Psychopharmacology: October 2007 - Volume 27 - Issue 5 - p 498-502
doi: 10.1097/JCP.0b013e31814db4c4
Brief Reports

Introduction: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric disorder. Cocaine use is particularly common in patients with bipolar disorder. Both cocaine use and bipolar disorder are associated with mood symptoms and cognitive impairment. Therefore, treatments that stabilize mood, improve cognition, and reduce cocaine use would be useful. Citicoline modulates phospholipids metabolism and neurotransmitter levels and appears to improve cognition in some central nervous system disorders. A 12-week, randomized, placebo-controlled, parallel-group, add-on, proof-of-concept trial of citicoline was conducted in 44 outpatients with a history of mania or hypomania and cocaine dependence. The primary aim was to examine memory, but mood and cocaine use were also assessed.

Method: Participants were evaluated with a structured diagnostic interview; Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, and Rey Auditory Verbal Learning Test. Cocaine use was assessed with urine drug screens. Data were analyzed using mixed-model analysis of covariance, generalized estimating equations, and logistic regression analyses that used all of the available data.

Results: A significant group effect (P = 0.006) favoring citicoline was observed on the Rey Auditory Verbal Learning Test alternative word list. No significant between-group differences were found on the Inventory of Depressive Symptomatology-Self-Report or Young Mania Rating Scale. The citicoline group had a significantly lower probability of a cocaine-positive urine at exit (P = 0.026). The covariate-adjusted odds ratio estimate was 6.41, suggesting that those who took placebo had 6.41-times higher odds of testing positive for cocaine at exit than those who took citicoline. Citicoline was well tolerated, with no participants to our knowledge discontinuing because of medication side effects.

Conclusions: The use of citicoline was associated with improvement relative to placebo in some aspects of declarative memory and cocaine use, but not mood. The findings are promising and suggest that larger trials of citicoline are warranted.

*Department of Psychiatry and †Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX.

Received August 29, 2006; accepted after revision June 5, 2007.

Funded by the Stanley Medical Research Institute.

Address correspondence and reprint requests to E. Sherwood Brown, MD, PhD, Department of Psychiatry, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-8849. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.