The Natural Substance Citicoline May Be Useful in Bipolar Disorder with Comorbid Stimulant Abuse

September 6, 2011 · Posted in Comorbidities, Potential Treatments 

Sherwood Brown and colleagues from the University of Texas Southwestern Medical Center have completed a successful placebo-controlled trial of citicoline for bipolar and unipolar depression with comorbid methamphetamine dependence. Forty-eight participants with methamphetamine dependence and either unipolar or bipolar depression were randomized to either citicoline (2000 mg/day) or placebo for 12 weeks. Those receiving citicoline had significantly greater improvement in scores on the Inventory of Depressive Symptoms compared with those who received placebo, and patients receiving citicoline stayed in the study significantly longer, with completion rates of 41% on citicoline and 15% on placebo.

In 2007, the same team of investigators reported in the Journal of Clinical Psychopharmacology that citicoline had positive effects in bipolar patients with cocaine dependence, who experienced significant decreases in cocaine use and fewer cocaine-positive urine tests while taking citicoline.



Citicoline is a cytosine di-phospholipid that contains choline and is rapidly metabolized to cytidine and choline. Both cytidine and choline have been reported to have positive psychotropic effects. A research group at Massachusetts General Hospital found that cytidine exerted significantly more antidepressant effects than placebo in bipolar depression (as reported in BNN Volume 12, Issue 3 from 2008). The dinucleotides, including cytidine and uridine, have been reported to exert antidepressant effects in patients with bipolar depression, further supporting the potential antidepressant utility of these compounds. Interestingly, those with greater numbers of prior episodes were more responsive to uridine (a finding that contrasts with those about most other potential antidepressant compounds in bipolar illness, in which patients who have experienced more episodes are less likely to respond well to treatment).

Editor’s note: The studies by Brown and colleagues are rare in that they directly assessed the efficacy of a treatment in patients with mood disorder and comorbid substance abuse. Most studies include only patients with substance abuse without comorbid mood disorder, so doctors are forced to make inferences from these data when determining how to treat patients with a primary unipolar or bipolar disorder. These studies of both cocaine dependence and methamphetamine dependence suggest a research-supported potential treatment approach for these comorbid conditions.


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