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Treating active cocaine use in patients with bipolar disorder presents formidable challenges. Pilot trial results have been positive for citicoline, an inexpensive dietary supplement with few adverse effects and no known drug–drug interactions. In animal studies, citicoline increases dopamine, norepinephrine, serotonin, and acetylcholine levels in various brain areas; is neuroprotective in ischemia models; and enhances cerebral metabolism and synthesis of structural phospholipids into membranes. Investigators analyzed results on 122 patients with bipolar I disorder (depressed or mixed mood) and cocaine dependence (mean age, 42; 67% men), who participated in a double-blind, placebo-controlled, 12-week trial of citicoline. Participants had active cocaine use; most had at least one other substance use disorder, predominantly alcohol and/or marijuana.
Citicoline was initiated at 500 mg/day, increasing to 2000 mg/day at 6 weeks. Patients were also taking stable doses of mood stabilizers for at least 2 weeks. All received treatment as usual plus weekly cognitive-behavioral therapy. Vouchers were awarded for attendance and urine samples.
Based on negative urine screens, citicoline showed modest superiority that progressively diminished, with a number needed to treat for one to benefit of 6.9 at week 1, 11.1 at week 6, and 43.8 at week 12. Overall, only 23% of citicoline recipients and 20% of placebo recipients abstained entirely. No group differences occurred in ratings of mood or craving or in adverse somatic effects or intercurrent events.
Brown ES et al. A randomized, double-blind, placebo-controlled trial of citicoline for cocaine dependence in bipolar I disorder. Am J Psychiatry 2015 May 22; [e-pub]. (http://dx.doi.org/10.1176/appi.ajp.2015.14070857)
Comment
These findings, together with earlier findings of modest benefits for relapse prevention, suggest some advantages for citicoline, although the results diminished with time. Whether longer-term benefits for cocaine dependence might emerge from alternative dosing schedules or combinations with other agents remains to be seen.