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Open Trial of Injectable Risperidone for Methamphetamine Dependence

Meredith, Charles W. MD; Jaffe, Craig MD; Cherrier, Monique PhD; Robinson, Joseph P. MSW; Malte, Carol A. MSW; Yanasak, Elisia V. PhD; Kennedy, Annette PsyD; Ferguson, Laura C. MD; Tapp, Andre M. MD; Saxon, Andrew J. MD

Journal of Addiction Medicine: June 2009 - Volume 3 - Issue 2 - p 55-65
doi: 10.1097/ADM.0b013e31818e2185
Original Article

We tested acceptability and tolerability of long-acting injectable risperidone for methamphetamine (MA) dependence in an open trial with the hypothesis that participants would reduce MA use. Participants were also evaluated for changes in neurocognitive function and psychiatric symptomology. Participants with MA dependence (n = 34) entered a 7-day open-label run-in with oral risperidone. Participants who tolerated oral risperidone (n = 22) were begun on long-acting injectable risperidone 25 mg intramuscular medication with subsequent injections q 2 weeks to a total of 4 injections. Participants remained on oral risperidone during the first 3 weeks after initial injection. Participants were offered 8 weekly individual sessions of relapse prevention counseling. At baseline, participants reported using MA an average of 4.1 days per week (SD = 1.9). Estimated mean days of MA use per week while on injections was 1.0 (95% confidence interval = 0.6–1.4), with days of use decreasing significantly from baseline through week 8 (β = −0.27; 95% confidence interval: − 0.38–−0.16; P < 0.001). Mean week 6 risperidone + 9-OH risperidone plasma levels for participants abstinent from MA from weeks 5 to 8 (n = 7, 63.6%) were 18.8 ng/mL (SD = 6.6) compared with 12.3 (SD = 4.0) for those not abstinent (n = 4; P = 0.075). No serious adverse events occurred. Verbal memory improved at week 4 compared with baseline (P < 0.05). Participation in this trial of injectable risperidone was associated with reductions in MA use as well as some positive benefits on verbal memory. However, these results are limited by the use of an open trial design with a high dropout rate. Risperidone deserves further study in controlled trials as a pharmacotherapy for MA dependence.

From the Mental Health Service (CWM, JPR, CAM, EVY, AK, LCF, AMT, and AJS), Center of Excellence in Substance Abuse Treatment and Education (CAM, LCF, and AJS), VA Puget Sound Health Care System; and Department of Psychiatry and Behavioral Sciences (CWM, CJ, MC, LCF, AMT, and AJS), University of Washington, Seattle, WA.

Received for publication April 23, 2008; accepted September 6, 2008.

Supported by a grant from Ortho-McNeil Janssen Scientific Affairs LLC and by the Center of Excellence in Substance Abuse Treatment and Education, VA Puget Sound Health Care System.

Dr. Cherrier has provided consultation to Solvay, Inc. and Merck, Inc.

Dr. Tapp has been on the speaker’s bureau and has received honoraria from AstraZeneca, Eli Lilly, and Janssen and has received research support from AstraZeneca and Eli Lilly.

Dr. Saxon has been on the speaker’s bureau and has received honoraria from Janssen LLC, Alkermes, Cephalon, Forest Pharmaceuticals, and Schering-Plough Canada. He has also provided consultation to Schering-Plough Europe.

The other authors have nothing to disclose and no conflicts of interest.

Send correspondence and reprint requests to Dr. Meredith, VA Puget Sound Health Care System (S-116A), 1660 S. Columbian Wy., Seattle, WA. e-mail:

© 2009 American Society of Addiction Medicine