A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder.

OBJECTIVE: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. METHOD: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. RESULTS: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. CONCLUSIONS: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. 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.

Impact of levetiracetam on mood and cognition during prednisone therapy.

PURPOSE: Corticosteroid excess is associated with impairment in declarative memory and hippocampal changes. In animals, phenytoin blocks the effects of stress on memory and hippocampal histology. Levetiracetam also shows neuroprotective properties in some animal models. This report examines whether levetiracetam prevents mood or cognitive changes secondary to prescription corticosteroids. MATERIALS AND METHODS: Thirty outpatients given systemic corticosteroid therapy for asthma were randomized to either levetiracetam (1500 mg/day) or placebo given concurrently with the corticosteroids. Mood was assessed with the Hamilton rating scale for depression (HRSD), Young mania rating scale (YMRS) and activation (ACT) subscale of the internal state scale, declarative memory with the Rey auditory verbal learning test (RAVLT), and attention and executive functioning with the Stroop color and word test at baseline and after approximately 7 days of corticosteroid plus levetiracetam or placebo therapy. RESULTS: Levetiracetam and placebo groups showed significant improvement from baseline to exit on RAVLT total words recalled with a non-significant change on other outcomes. No significant between-group differences were found. Initial prednisone dose showed a significant correlation with change in some cognitive domains. CONCLUSIONS: Levetiracetam was well tolerated when combined with prednisone. Significant between-group differences in mood and cognition were not found.