Clonidine Helps to Maintain Opioid Abstinence

Joel Yager, MD reviewing Kowalczyk WJ et al. Am J Psychiatry 2015 Mar 17.

By buffering stress, clonidine added to buprenorphine treatment lowered cravings and prolonged abstinence.

Despite buprenorphine treatment, opiate-dependent individuals are at risk for relapse, particularly during stressful periods. In a study based on animal models showing that α-2 adrenoceptor agonists helped to block stress-induced reinstatement of drug seeking, investigators enrolled 118 heroin-dependent individuals (mean age, 39; men, 78%; black, 60%). They were randomized to 20 weeks of add-on clonidine (dose gradually increased from 0.1 mg to 0.3 mg daily and adjusted as needed) or placebo.

Participants had used heroin or prescription opioids for a mean of 12 years (poly-substance abusers, 17%) and were currently drug-free and maintained on 8 mg to 24 mg buprenorphine daily. They were prompted at random intervals to record ongoing cravings and stress levels (“ecological momentary assessments”) in electronic diaries. Urine was tested periodically for opioids and tetrahydrocannabinol (THC).

Results controlled for prior cocaine use. Compared with placebo, clonidine increased time to opioid lapse (but not relapse) and number of consecutive days of abstinence, and it decreased the number of THC-positive urine tests. Ratings of cravings were linearly associated with stress ratings. For all but the highest stress levels, clonidine blunted this association, decoupling cravings from stress. However, clonidine did not blunt cravings associated with environmental drug cueing (e.g., being in the presence of heroin).

CITATION(S):

Kowalczyk WJ 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; [e-pub].