• Psychiatry Clinical Trials
• Substance-Related Disorders

The National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study found that patients who tapered off prescription opioids using buprenorphine during a 9-month period, whether initially or after a period of improvement, almost universally relapsed. “There has been virtually no research on the treatment of persons dependent on prescription opioids, in spite of the major increase in prescription opioid abuse and in the numbers of persons entering treatment for addiction to prescription opioids,” said Roger D. Weiss, MD, Harvard Medical School, Boston, and McLean Hospital, Belmont, MA.

The study, which is the largest treatment study ever conducted for prescription opioid dependence (POD), sought to determine the optimal length of pharmacotherapy and the value of intense counseling.

The study investigated whether adding intense counseling to buprenorphine-naloxone plus standard medical management improved patient outcomes, what duration of buprenorphine is best, and whether chronic pain influenced outcomes.

The study enrolled 653 persons at 10 sites with POD and offered them standard medical management, which included buprenorphine (12–16 mg maximum, adjusted for addiction), an initial 1-hour visit, and weekly 20-minute sessions with a physician who counseled them and monitored for drug side effects. Half of the group remained in this standard medical management (SMM) arm while half received enhanced medical management (EMM) that included twice-weekly 60-minute individualized drug counseling sessions that were focused on interpersonal issues, coping with triggers, and high-risk situations.

Patients were evaluated after periods of individualized buprenorphine tapering and maintenance and were assessed for abstinence from opioids at various periods.

All patients had a DSM-IV diagnosis of opioid dependence and had used opioids for at least 20 of the past 30 days. The average subject was 33 years old and had been using opioids for 4.5 years, including sustained-release oxycodone (35%), hydrocodone (32%), immediate-release oxycodone (19%), methadone (6%), and others (8%). For 70% of subjects, this was the first treatment for opioid dependence.

Patients reported current chronic pain (42%), a history of heroin use (23%), alcohol abuse (60%) or dependence (27%), cannabis abuse (47%) or dependence (15%), and cocaine abuse (32%) or dependence (18%).

Treatment success was defined as ≤ 4 days of opioid use per month, no positive urine screens for opioids for 2 consecutive weeks, no other formal substance abuse treatment, and no opioid injections.

Phase 1 included 1 month of tapering and 2 months of stabilization. At the end of this period, few patients were successfully treated, and enhanced management did not influence the results. In the SMM group, only 7% met the criteria for success, as did just 6% of the EMM group (p=0.45). “Nearly all patients relapsed after a 4-week taper,” Dr. Weiss reported.

Patients (n=360) who relapsed entered Phase 2, were randomized again to SMM or EMM and received 3 months of buprenorphine stabilization, and then had treatment tapered for 1 month, with a 2-month follow-up.

At the end of stabilization (Week 12), substantial improvement (abstinence for ≥ 3 of the final 4 weeks of buprenorphine stabilization by urine-confirmed self-report) was noted for 52% of the EMM group and 47% of the SMM group, though there was no additional benefit to enhanced management (p=0.3).

“We went from an average success rate of 49% to 26% at Week 16,” Dr. Weiss reported. At Week 24 (8 weeks posttaper), only 9% of patients remained successfully treated. “At the end of the study, 7 of 8 patients doing well on buprenorphine maintenance had relapsed.”

The only predictor of outcome was lifetime use of heroin. At Week 12, improvement was noted for 37% of those who reported lifetime heroin use, compared with 54% of those without a history (p=0.003); at Week 24, this was 5% and 10%, respectively (p=0.13). The presence of chronic pain did not influence outcomes. Chronic pain patients were equally likely to have early treatment failure and equally likely to be substantially improved at Week 12 of phase 2 (53% vs 47% for those without chronic pain).

Over half of the subjects reported at least moderate reduction of pain from baseline (≥30%), and one-third had a substantial improvement (≥50%).

• © 2010 MD Conference Express