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Clonidine, and Prolonging Opiate Abstinence By Reducing Stress-Induced Craving
In Session With William J. Kowalczyk, PhD:
Clonidine, and Prolonging Opiate Abstinence By Reducing Stress-Induced Craving
William J. Kowalczyk, PhD
Postdoctoral Fellow, NIDA Intramural Research Program, Clinical Pharmacology & Therapeutics Branch, Baltimore, Md.
First published in Psychiatry Weekly, Volume 10, Issue
1, on April 27, 2015
Q: How do alpha-2 agonists, such as clonidine, lend themselves to addiction treatment?
A: For relapse prevention, alpha-2 agonists were identified as a promising class of medications by the “reinstatement model” in rats: they were among the medications that blocked reinstatement (relapse) of drug seeking induced by stress. In the same animal model, chronic buprenorphine or methadone blocked reinstatement of drug seeking induced by a priming dose of drug. Because blocking two types of relapse may be better than one, we designed a clinical trial to look specifically at how clonidine might help people during buprenorphine maintenance. Clonidine is already given regularly for withdrawal symptoms in opiate and alcohol addiction recovery, so we believed it would be relatively well tolerated in our sample.
Q: What sort of methodological components did you employ to capture stress and craving levels?
A:We used ecological momentary assessment (EMA) to randomly assess mood and behavior in real time. Participants were issued a handheld device that rang randomly 4 times/day. Participants responded to questions about the presence of stress or craving by choosing “NO!!”, “no??”, “yes??”, and “YES!!”.
Our study included 208 opioid-dependent patients receiving buprenorphine at an outpatient facility. Following 4 weeks of buprenorphine treatment, participants were required to remain abstinent for a period of =2 weeks in order to be randomized to adjunctive clonidine or placebo. Abstinence was assessed with urine tests 3 times/week. Of the initial sample, 118 participants were randomized to receive clonidine (N=61) or placebo (N=57) for 14 weeks.
Q: How did clonidine affect overall time to relapse and stress-induced relapse?
A: We found a small but significant effect of clonidine in the length of time until the participant had an opiate lapse, as opposed to relapse. Clonidine was also associated with a longer duration of abstinence (34.8 days [SD=3.7] compared to placebo (25.5 days [SD=2.7]).
EMA data revealed that clonidine in conjunction with buprenorphine diminished the likelihood of heroin craving in periods of moderate stress. At moderate levels of stress, the likelihood of reporting any craving for heroin was ~7% in the clonidine group compared to ~20% in the placebo group. At the highest levels of reported stress, there was no significant difference in craving between the clonidine and placebo groups. The most frequently reported level of stress was “no stress at all.”
It’s important to note that the clonidine and placebo groups reported similar levels of overall stress. Clonidine does not specifically act on stress—it appears to act on the reaction to stress. The idea of protection from stress-induced lapses may actually reach across different drugs, and there are a handful of other studies testing clonidine and other similar medications in patients using various drugs of abuse. When those results are published, we’ll know if this is a common pathway across multiple drugs of abuse, or if it’s something that’s more effective specifically for opiate treatment.
Disclosure: Dr. Kowalczyk reports no affiliations with, or financial interests in, any organization that may pose a conflict of interest.
References:
Kowalczyk WJ, Phillips KA, Jobes ML, et al. Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. Am J Psychiatry. 2015 Mar 17. [Epub ahead of print]