Naltrexone is an FDA-approved treatment for alcohol dependence, and several large, randomized, clinical trials support its efficacy for this indication. Bipolar disorder is a severe and persistent psychiatric illness affecting 1.2-1.6% of the population, and is associated with a 46% lifetime prevalence of alcohol related disorders. When present in patients with bipolar disorder, alcohol dependence is associated with increased rates of hospitalization, poor outcome during hospitalization, violence towards self and others, and non-adherence to bipolar disorder treatment. Thus, effective treatment of patients with bipolar disorder and alcohol dependence is a major public health concern. To date, no randomized, double-blind, placebo controlled trials have been conducted in patients with bipolar disorder and alcohol dependence. Our group has developed a research program that conducts clinical trials of medications in persons with bipolar disorder and substance-related disorders. We have collected open-label data suggesting that naltrexone is safe, well tolerated, and potentially effective in reducing alcohol use in patients with bipolar disorder and alcohol dependence. Patients with bipolar disorder are challenging to treat, often requiring frequent changes in medication to control symptoms of mania, depression, or both. Therefore, the design of an appropriate trial to examine the efficacy of medications for alcohol dependence is challenging in bipolar disordered patients. For this reason, a double-blind, placebo-controlled pilot study is proposed to examine the feasibility and safety of a controlled trial of naltrexone in patients with bipolar disorder, and to examine which outcome measures are preferred and which patient types should be included in a subsequent larger, more definitive, controlled clinical trial. A 12-week randomized, double-blind, placebo-controlled, pilot study of naltrexone add-on therapy in 50 outpatients with bipolar I or II and current alcohol dependence is proposed. Each participant will also receive manual-driven cognitive behavioral therapy specifically designed for patients with bipolar disorder and substance dependence. To standardize management of concomitant medication (e.g., mood stabilizers, antidepressants), both groups will receive algorithm-based treatment based on guidelines of the Bipolar Disorder Module of the Texas Medication Algorithm Project. Alcohol use is the primary outcome, and alcohol craving is the secondary outcome. Manic and depressive symptom severity and the relationship between changes in alcohol use and changes in mood will be expIored.
|Brown, E Sherwood; Carmody, Thomas J; Schmitz, Joy M et al. (2009) A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res 33:1863-9|
|Mitchell, Joshua D; Brown, E Sherwood; Rush, A John (2007) Comorbid disorders in patients with bipolar disorder and concomitant substance dependence. J Affect Disord 102:281-7|