A randomized, double-blind, placebo-controlled trial of citicoline for bipolar and unipolar depression and methamphetamine dependence

J Affect Disord. 2012 Dec 20;143(1-3):257-60. doi: 10.1016/j.jad.2012.05.006. Epub 2012 Sep 11.


Background: Methamphetamine use disorders are common and severe problems. Persons with mood disorders, particularly bipolar disorder, have high rates of substance use disorders. We previously reported promising findings on drug use, memory and study retention in patients with a history of mania and cocaine dependence given the nutritional supplement citicoline. In the current proof-of-concept study, we examined citicoline in bipolar or unipolar depression and methamphetamine dependence.

Methods: Sixty adults with bipolar depression or major depressive disorder and methamphetamine dependence were randomized to citicoline (2000mg/day) or placebo for 12 weeks. Mood was assessed using Inventory of Depressive Symptomatology-Clinician Version (IDS-C), and cognition with the Hopkins Auditory Verbal Learning Test (HVLT). Drug use was assessed by urine drug screens.

Results: An ANCOVA of the intent-to-treat sample showed that those receiving citicoline (n=28) had a statistically significantly greater improvement in IDS-C scores than those receiving placebo (n=20). Survival in the study was significantly longer and completion rates significantly greater with citicoline than placebo. No significant differences were observed in memory or methamphetamine use. Citicoline was well tolerated.

Limitations: Sample heterogeneity and small sample size were limitations.

Conclusions: To our knowledge this is the first placebo-controlled trial in a dual diagnosis sample with methamphetamine use disorders. Findings suggest that citicoline may have antidepressant properties in this population. Greater treatment retention with citicoline is also noteworthy in a patient population with substance dependence. Larger trials targeting depressive symptoms and treatment retention seem warranted.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amphetamine-Related Disorders / diagnosis
  • Amphetamine-Related Disorders / drug therapy*
  • Analysis of Variance
  • Antidepressive Agents / therapeutic use*
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Cytidine Diphosphate Choline / therapeutic use*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Diagnosis, Dual (Psychiatry)
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methamphetamine*
  • Middle Aged
  • Young Adult


  • Antidepressive Agents
  • Methamphetamine
  • Cytidine Diphosphate Choline