Early Phase II Trials for Cocaine Medication Development - 1

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.

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.