Nancy A. Melville

December 09, 2013

SCOTTSDALE, Arizona — Catechol-O-methyltransferase (COMT) inhibitors provide an anticraving effect that can improve adherence to buprenorphine maintenance treatment for opioid addiction among patients who have otherwise failed the treatment regimen, new research shows.

"In this population, we demonstrated through use of COMT inhibitor a significant treatment adherence and/or survival of 70% of subjects," said first author Rahim Shafa, MD, of the MetroWest CNS Research Center, in Milford, Massachusetts.

"In addition, these individuals were all treatment- and sobriety-compliant, not only according to their report of medication compliance or pill count but also with consistently negative urine toxic screenings," Dr. Shafa told Medscape Medical News.

The findings were presented here at the American Academy of Addiction Psychiatry (AAAP) 24th Annual Meeting & Symposium.

Painful Withdrawal Symptoms

Opiate antagonists, particularly buprenorphine, in opioid maintenance treatment are associated with significantly painful withdrawal symptoms.

Previous research has shown that COMT inhibitors can help in the successful detoxification of buprenorphine, methadone, and other opiates, owing to their ability to help balance dopamine, which is central to the reward/dependence pathway that leads to intense craving.

The new study looked at a larger population of 253 opiate-dependent patients who had failed to comply with initial buprenorphine maintenance treatment and followed them for a longer duration of 30 months.

The patients received the COMT inhibitor entacapone (200 - 1000 mg/day) in addition to their buprenorphine treatment; their treatment adherence and efficacy were followed for the 30 months through bimonthly follow-up visits, urine screening, and interviews.

Among the 253 patients, 67 (26.5%) failed to remain abstinent for 6 months or dropped out of the study for nonadherence.

But 186 patients (73.5%) did remain abstinent for longer than 6 months: 84 (32.2%) remained abstinent for 6 to 12 months; 61 (24.1%) for 12 to 24 months; and 41 (16.2%) for 24 to 30 months (P < .01).

Forty-one of the patients (16.2%) were able to achieve abstinence with long-acting naltrexone.

First Study of Its Kind

Patients reported minimal side effects, with sleepiness, headaches, and dizziness among the most frequently reported reasons for discontinuation.

"This is the first study of its kind, demonstrating COMT-Inhibitors' anti-craving effects, through dopamine-reward pathway modulation, can be utilized in opiates maintenance treatment without inducing withdrawal symptoms," the authors write.

Dr. Shafa underscored the importance of any improvement in the adherence rates among the population of patients who repeatedly fail opiate addiction treatment.

"It is a well-known phenomenon that these patients represent the majority of the population who end up doing medication (buprenorphine) diversion and/or most tragically end up dead of accidental opiate overdoses," he said.

Dr. Shafa further noted that efficacy of COMT-inhibitor treatment was set at 6 months because of the known diminishment of the anticraving effect provided by buprenorphine or methadone that typically occurs after the first 3 months of treatment.

"By the end of 1 year, the opiate anticraving effect of either methadone or buprenorphine is equal to placebo," he said.

"So we chose the 6-months landmark as the bar for treatment and clinical efficacy to demonstrate the clear quality of the opiate anticraving effect of COMT inhibitor and to be sure that the results were free from any statistical noise of pseudo success that might have resulted from the mere compliance with buprenorphine."

Helpful Tool

The study is important in evaluating a potential means to help improve adherence to maintenance treatment of opioid addiction, said Olivera Bogunovic, MD, a psychiatrist in charge of the residential and partial program and associate program director of Partners Addiction Psychiatry Fellowship, in Belmont, Massachusetts.

"Even with buprenorphine maintenance therapy, abstinence remains a challenge for some patients because of the presences of cravings," Dr. Bogunovic told Medscape Medical News.

"Any medication or individual therapy that can reduce the cravings would be a very important and helpful tool."

The authors and Dr. Bogunovic report no relevant financial relationships.

American Academy of Addiction Psychiatry (AAAP) 24th Annual Meeting & Symposium: Abstract 44, presented December 7, 2013.


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