Do Atypical Antipsychotics Effectively Treat Co-Occurring Bipolar Disorder and Stimulant Dependence? A Randomized, Double-Blind Trial

Vicki A. Nejtek, Ph.D.; Matthew Avila, Ph.D.; Li-Ann Chen, M.A.; Tanya Zielinski, M.D.; Marija Djokovic, M.D.; Alan Podawiltz, D.O.; Kathryn Kaiser, B.S.; Sejong Bae, Ph.D.; and A. John Rush, M.D.

Objectives: The primary objective was to compare the efficacy and tolerability of quetiapine and risperidone in the treatment of mood symptoms, drug cravings, and drug use in outpatients with concurrent DSM-IV-defined bipolar I or II disorder and cocaine or methamphetamine dependence.

Method: Men and women of all ethnic origins, 20 to 50 years of age, were eligible to participate. Persons were excluded if they were inpatients, met DSM-IV criteria for substance-induced mood disorder, had any other substance dependence, were euthymic or suicidal, had any life-threatening illnesses, or were currently receiving antipsychotic medications. Duration of the trial was 20 weeks. Study participants attended weekly visits and were evaluated for mood symptoms, drug cravings, drug use, and medication side effects. Treatment outcomes were analyzed using linear mixed models. Fixed-effects terms for medication group, study week, and group-by-study-week were included in the models. The study was conducted between October 2002 and November 2006.

Results: Of 124 consenting outpatients, an evaluable sample of 80 patients who attended baseline and at least 1 follow-up study visit was formed. The mean ± SD exit dose for quetiapine was 303.6 ± 151.9 mg/day and 3.1 ± 1.2 mg/day for risperidone. Both quetiapine (N = 42) and risperidone (N = 38) significantly improved manic and depressive symptoms and reduced drug cravings (p < .0005) compared to baseline. Decreased drug cravings were related to less frequent drug use (p = .03). The 2 medications did not significantly differ in their effects on mood symptoms, drug craving, or drug use.

Conclusions: Relative to baseline mood and drug-craving status, both quetiapine and risperidone were associated with manic, mixed, and depressive symptom improvement and reduced drug cravings. Both medications were well tolerated. The interpretation of these results is limited by the absence of a placebo control.

Trial Registration: clinicaltrials.gov Identifier: NCT00227123

(J Clin Psychiatry 2008;69:1257-1266. Online Ahead of Print July 29, 2008.)

Received May 5, 2007; accepted Jan. 11, 2008. From the University of North Texas Health Science Center at Fort Worth (Drs. Nejtek, Avila, Djokovic, Podawiltz, and Bae and Ms. Kaiser); and the University of Texas Southwestern Medical Center at Dallas (Drs. Nejtek, Zielinski, and Rush and Ms. Chen).

This study was funded with a clinical trials grant awarded to the principal investigator (V.A.N.) by the Stanley Medical Research Institute (Chevy Chase, Md.). This research was also conducted with support from the Investigator-Sponsored Study Program of AstraZeneca (Wilmington, Del.), which provided the study drug, quetiapine.

Presented in part at the 48th annual meeting of the New Clinical Drug Evaluation Unit, May 27-30, 2008, Phoenix, Ariz., and at the 70th annual meeting of the College on Problems of Drug Dependence, June 14-19, 2008, San Juan, Puerto Rico.

The authors acknowledge Michael Phan, Pharm.D., and Paul Nguyen, Pharm.D., of Investigational Drug Services at the University of Texas Southwestern Medical Center in Dallas, who managed all study medication protocols. Drs. Phan and Nguyen report no financial or other relationship relevant to the subject of this article.

Dr. Nejtek served on the AstraZeneca speakers bureau from 2001-2005. Dr. Rush has provided scientific consultation to or served on advisory boards for Advanced Neuromodulation Systems, AstraZeneca (beginning March 2007), Best Practice Project Management, Bristol-Myers Squibb, Cyberonics, Forest, Gerson Lehman Group; GlaxoSmithKline; Jazz, Eli Lilly, Magellan Health Services, Merck, Neuronetics, Ono, Organon, PamLab, Personality Disorder Research, Pfizer, The Urban Institute, and Wyeth-Ayerst; has been on speakers bureaus for Cyberonics, Forest, GlaxoSmithKline, and Eli Lilly; owns stock in Pfizer; and has received royalties from Guilford Publications and Healthcare Technology Systems. Drs. Avila, Zielinski, Djokovic, Podawiltz, and Bae and Mss. Chen and Kaiser report no additional financial or other relationship relevant to the subject of this article.

Corresponding author and reprints: Vicki A. Nejtek, Ph.D., University of North Texas Health Science Center at Fort Worth, Department of Psychiatry, 3500 Camp Bowie Blvd., Fort Worth, TX 76107 (e-mail: vnejtek@hsc.unt.edu).