Adjunctive Drug Lengthens Abstinence in Buprenorphine Therapy

Adding a commonly used drug to buprenorphine treatment increased the duration of abstinence for opioid-dependent patients, according to a study by researchers at the National Institute on Drug Abuse (NIDA) published online March 18 in AJP in Advance.

The study drug, clonidine, is often used to dampen symptoms of opioid withdrawal and does not have special prescribing requirements, as buprenorphine and methadone do.

Overall, clonidine lengthened the time to opioid lapse (defined as a positive or missing urine test), but not significantly. However, after controlling the results for cocaine use, the researchers found that taking clonidine “significantly increased the time to initial opioid lapse.”

“The average effect—a nine-day increase in time to lapse—was not huge, but we think of it in terms of a principle that one of our behavioral-psychologist colleagues sometimes expresses as ‘abstinence begets abstinence,’ ” said study director Kenzie Preston, Ph.D., a senior investigator at NIDA’s Clinical Pharmacology and Therapeutics Research Branch in Baltimore, in an interview with Psychiatric News. “The longer you can be abstinent from a drug of abuse for any reason, the better you’ll do in the long run.”

In addition, the average time to lapse didn’t tell the full story, said Preston.

Only four of 57 people on placebo stayed abstinent for more than 50 days, compared with 21 of 61 people on clonidine. Also, 10 of those 21 participants remained abstinent for the full 12 weeks they were taking clonidine. “We think it’s exciting that even a substantial minority of people seemed to get a large benefit from clonidine maintenance,” she said.

“We want to prevent relapse, and we want people to stay in treatment and return to good functional levels—and relapse can jeopardize that,” said Rajita Sinha, Ph.D., a professor of psychiatry, neurobiology, and child study at Yale University School of Medicine. “Here’s a tool we can use to help sustain that recovery for heroin- and opioid-dependent individuals.”

The 118 participants began the trial on buprenorphine. Once abstinent from opioids for two weeks, they were randomized to either clonidine or placebo. Time to relapse (two or more lapses) was not extended significantly, possibly because of the priming effect of the drug use in the first lapse.

As part of the trial protocol, participants received small electronic devices that prompted them four times a day to record stress, mood, craving, and any drug-related cues around them.

This “ecological momentary assessment” (EMA) has been increasingly used over the last decade in clinical settings and was applied in this study as a way to overcome recall bias. Craving for drugs often intensifies as stress increases, but ecological momentary assessment permitted a decoupling of at least moderately high levels of stress from craving.

“They may feel stressed, but they don’t have the same urgency for using drugs,” Sinha said of the subjects.

The NIDA researchers are looking at EMA and other data to predict who is at risk of lapse and when it happens.

Use of the EMA also added to evidence supporting animal models of stress and drug use and may help individualize treatment by identifying patients who lapse because of stress rather than drug cues or priming doses.

“We can’t recommend EMA for routine clinical use in addiction at this point, but we’re working to get it there and to make it the basis of interventions as well,” said Preston.

Clonidine is an alpha-2 adrenoreceptor agonist whose side effects include hypotension and sedation. However, those effects may be manageable over a longer time if patients are coming into the clinic regularly, as they are in buprenorphine treatment, said Sinha.

“We do not now have any medications in the addiction field that specifically target stress and that are also really effective with craving,” she said. “So this is a novel and important study.” ■

An abstract of “Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized, Controlled Trial With Ecological Momentary Assessment” can be accessed here.