A readily available over-the-counter nutritional supplement may help reduce illicit drug dependency in patients with psychiatric illness, according to researchers at the University of Texas Southwestern Medical Center.
In a study published over the summer in the American Journal of Psychiatry,the Texas researchers showed that supplementation with citicoline was effective at lowering cocaine use in individuals dual-diagnosed with bipolar I disorder and cocaine dependence.
Citicoline, a naturally occurring exogenous form of cytidine 5ʹ-diphosphate choline, seems to support brain health in a number of ways. It plays a key role in the biosynthesis of membrane phospholipids and modulates neurotransmitter levels. It appears to improve cognition in some central nervous system disorders and has been shown to be neuroprotective in animal models (Dávalos, et al. Lancet. 2012; 380(9839): 349-357).
The new findings suggest that citicoline holds great promise as a safe alternative therapy for an often difficult-to-treat population.
Bipolar & Substance Abuse
Substance abuse is remarkably common in patients with psychiatric disorders. Rates are particularly high in individuals with bipolar disorder, among whom cocaine use is especially prominent.
Drug dependence further complicates an already complex illness. Previous studies have documented increased hospitalization rates, higher incidence of aggression and violence, lower rates of recovery during hospitalization, and poorer medication adherence in patients with both bipolar and substance abuse disorders.
Scientists aren’t entirely sure why the rates of drug abuse are so high in people with bipolar disorder, though there are many possible explanations. The classic features of bipolar disorder -- such as impulsivity -- might lead to a greater risk of abuse. Exposure to substances being sold or used in a patient’s living environment or elsewhere may be a factor as well. It’s also possible that an underlying genetic vulnerability may contribute to substance abuse.
Having a diagnosis of bipolar disorder is associated with poor response to drug dependency treatment, which typically consists of prescription pharmaceuticals combined with counseling and behavioral therapy. But some researchers, like the group at the University of Texas, are now exploring novel treatment options for this vulnerable patient population.
Citicoline for Drug Users
Sherwood Brown, MD, PhD, professor of psychiatry at the UT Southwestern Medical Center and lead researcher of the citicoline study, notes that when he first entered the field, the literature clearly indicated that a majority of patients with bipolar disorder also had longstanding substance abuse issues.
Despite this striking correlation, “most clinical trials excluded people with substance abuse, and there was little research on the treatment of patients with both bipolar disorder and substance dependence.”
Recognizing an unmet need, he and his colleagues conducted a pilot study to investigate the efficacy of citicoline in preventing cocaine relapse in bipolar patients with a history of cocaine dependence. The hypothesis was based on earlier work suggesting that citicoline might decrease cocaine dependency.
The initial data showed that citicoline was more effective than placebo at decreasing the risk of relapse to cocaine use. These findings set the stage for the current study, which involved active cocaine users with bipolar diagnoses.
A cohort of 130 adult outpatients with bipolar I disorder and current cocaine dependence were recruited for this randomized, double-blind, placebo-controlled trial. All had self-reported cocaine use within the seven days prior to the study’s onset. Additionally, they all had cocaine-positive urine screens at baseline (Brown ES et al. Am J Psych. 2015. Advance online publication)
Over the course of 12 weeks, patients received either Cognizin® citicoline (Jarrow® Formulas) or placebo add-on therapy. In the first week, participants in the citicoline group took 500 mg/day of the substance, or an identical placebo. The dose was increased to 1,000mg/day at week two, 1,500mg/day at week four, and 2,000 mg/day at week six.
The researchers monitored adherence using a Medication Event Monitoring System cap, and collected urine samples from all participants three times per week.
In order to improve retention, participants also engaged in manual-based cognitive behavioral therapy (CBT) designed specifically for patients with bipolar and substance use disorders. They received CBT twice weekly in the first four weeks followed by weekly sessions for the duration of the study, for a total of 16 sessions.
"A Useful Choice"
After 12 weeks, the researchers found that, based on participants’ urine screens, cocaine use had decreased significantly in the citicoline group. They reported significant treatment group (F=5.2,df=1, 1351, p=0.022) and group-by-time effects (F=5.9, df=1, 1351, p=0.015).
Citicoline was safe and well tolerated, with no significant differences in side effects or treatment retention between the citicoline and placebo groups.
Its “favorable safety profile and absence of known drug-drug interactions may make citicoline a useful choice in bipolar disorder and cocaine-dependent patients who are taking a variety of concomitant medications,” the authors suggest.
Furthermore, the reduction in cocaine use appeared to occur without affecting participants’ mood. This suggests that the decreased drug dependence was not contingent upon the initial stabilization of patients’ moods, Brown notes.
He adds that while the participants’ lack of mood change during treatment could be a result of the study’s design, it may also indicate a deeper and yet unknown mechanism through which citicoline reduces cocaine dependence.
The study included patients who were generally depressed with “rather mild manic symptoms, so there really wasn’t much opportunity to see a change in manic symptoms,” Dr. Brown explains. “But there was potential to see a change in depressive symptoms, and we just didn’t see it. So it looks like whatever mechanism citicoline is decreasing cocaine use with is probably not a secondary effect of an improvement in mood.”
“In terms of the broader generalizability of the study,” Brown continues, “this may be a positive finding,” suggesting that the efficacy of citicoline could extend beyond the dual-diagnosed study group to a much broader population. In other words, it might also be effective in treating pure cocaine use in individuals who don’t have co-occurring mood disorders.
The authors write that participants’ “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.”
Dr. Brown posited several possible explanations for this finding. “A lower dose might have been more effective than the dose we chose,” he speculates; it may also be true that “if the effect [of citicoline] tends to wear off, further increases in dose might be necessary.” Patients might also be developing a tolerance to the supplement. “It’s really hard to know the answer because there’s some evidence to suggest either possibility,” he adds.
Given these findings, citicoline supplementation may be most effective as an acute treatment option, rather than as a long-term therapy. The authors propose that it could be used as an initial strategy to reduce cocaine use in inpatient settings while future treatments are established.
Though the findings are promising, Dr. Brown believes that it’s too soon to recommend the widespread use of citicoline as a substance use treatment.
His team will continue the research using citicoline in patients using substances other than cocaine, including a current alcohol abuse trial. They hope to conduct a larger trial in patients with bipolar and substance use disorders as well, “perhaps with differences in dose and longer follow up.” Additionally, Dr. Brown says he is interested in looking at citicoline supplementation in patients with pure cocaine use not associated with a mood disorder.
As future studies continue to illuminate citicoline’s beneficial treatment effects, its favorable safety and side effect profile make it a promising potential therapy for patients with comorbidities or who may be using various other medications to treat substance use.