Opioid Maintenance: Optimal Stabilization & Withdrawal

描述：（由申请人提供）

DESCRIPTION: (provided by applicant) Opioid dependence is a recurring problem. Methadone and LAAM are effective therapeutic agents similar in many respects. Yet some features of dosing are not well defined. Two studies will be conducted examining dosing and dose reduction strategies in agonist (LAAM) treatment of opioid dependence. Results of the two linked, but distinct, studies of LAAM administration will be generalizable to methadone or buprenorphine. Study I will be a 5 month blind dosing study with three dose stabilization strategies and a Cognitive Behavior Therapy (CBT) base4ine. There will be three groups of 26 subjects each: 1) LAAM stabilization based on mg/kg weight/day+CBT (e.g., at 70 kg, dose will be 490 per week, distributed at 29 percent Monday, 29 percent Wednesday, and 42 percent Friday; 2) LAAM stabilization based on opioid negative urine screens and self reported symptoms+CBT; 3) LAAM stabilization at 50 mg per day equivalent+CBT (i.e., 350 per week distributed 29 percent, 29 percent, 42 percent). All subjects will be screened with the SCID, drug history, and medical evaluation based on our well-defined and rigorous techniques. A positive urine screen and clear evidence of current use, along with evidence of 5 years of use will be required. Cocaine and other drug use at intake and during treatment will be measured but will not be a condition for entry or exclusion. However, concurrent dependence (except nicotine) will be exclusionary. This study will elucidate dosing strategies. The study is based an our work with methadone, experience using a 1.1 mg/kg methadone dose, discussion with clinicians and researchers, and the methadone and LAAM literature. Study II will examine dose reduction strategies over a six-month period. Baseline therapy will be enhanced Clinical Management that recalls/reviews skills acquired in Study I. Only subjects enrolled in Study I and meeting the criteria for entry (low rate positive opioid screens and measured "Readiness to Change") will be accepted. Dose will be distributed as in Study I (29 percent/29 percent/42 percent). LAAM dose reduction will be at approximately 10 percent per week to 15-20 percent of initial dose and then discontinued. Two groups, 28 subjects each, will be 1) blind dose reduction and 2) open dose reduction. Screening/measurement will continue as in Study I. Blind group subjects will continue to receive placebo to study end. Retaining subjects even after reaching discontinuation will permit direct follow-up and there will be a one-month follow-up after the last visit. The work extends our initial preliminary examination of the blind-open procedure. In combination, the two studies will elucidate consequences of different dosing strategies and should enhance treatment.