Early Phase II Trials for Cocaine Medication Development - 1

The purpose of this study is to develop models for early Phase II testing of potential medications for cocaine dependence: amoxapine, risperidone and other agents. The study was a controlled pilot trial of risperidone in opiate-dependent patients on methadone maintenance. The study explored whether risperidone reduced cocaine use, cocaine craving, and cocaine subjective effects in patients on methadone maintenance who abused cocaine and whether it had an acceptable side effect profile. This

This was an 18-week prospective, randomized, placebo-controlled crossover design with placebo lead-in phase and terminal placebo phase. After two weeks of single-blind placebo, patients were randomly assigned to one of two schedules of medication: 2 Week Baseline Weeks 1-6 Weeks 7-12 Weeks 13-18 Group 1 placebo risperidone placebo placebo Group 2 placebo placebo risperidone placebo The first 6-week phase provided an initial double-blind medication-placebo comparison. In the second six-week phase (weeks 7-12), patients crossed over to the opposite treatment. During weeks 13-18, Group 1 patients remained on placebo while Group 2 patients were tapered from risperidone to placebo. For six weeks after the end of the trial, patients were offered routine clinical treatment with counseling and psychiatrist visits as needed. Medication dosage was titrated upwards on a fixed-flexible schedule to a maximum dose of 4 mg per day. Medication began at ½ mg risperidone for 3 days, then 1 mg for four days, 2 mg per day during week 2, 3 mg per day during week 3, and 4 mg per day during weeks 4-6. The titration schedule for risperidone in weeks 7-12 was the same as for weeks 1-6. In addition to treatment as usual, patients received a modified manual-guided relapse prevention counseling program in weekly meetings lasting approximately 20 minutes; these sessions provided cognitive and behavioral skills that were found to be helpful to patients in reducing cocaine use.

Modified manual guided relapse prevention counseling. Weekly 20 minute sessions consisting of cognitive behavioral skills. Both arms will receive this intervention.

Using the Modified Systemic Assessment for Treatment Emergent Effects the psychiatrist assessed side effects

Inclusion: good standing at methadone maintenance program DSM-IV criteria for cocaine dependence or abuse used cocaine at least 4 times in last month able to give informed consent Exclusion criteria currently meets DSM-IV criteria for Major depression or dysthymia meets DSM-IV criteria for attention deficit hyperactivity disorder, bipolar disorder, schizophrenia or any psychotic disorder history of seizures history of allergic reaction to risperidone chronic organic mental disorder significant current suicidal risk pregnancy, lactation or failure to use adequate birth control (for females) unstable physical disorders that may make participation hazardous coronary vascular disease cardiac conduction system disease as indicated by QRS duration >/= 0.11 current use of other prescribed psychotropic medications history of failure to respond to a previous adequate trial of risperidone history of neuroleptic malignant syndrome, tardive dyskinesia, or severe extrapyramidal reactions to neuroleptic medications current DSM-IV criteria for another substance dependence other than nicotine.