Clonidine Reduces Lapses Among People with Opioid Use Disorder Who Achieved Abstinence with Buprenorphine

In laboratory-based studies, alpha-2 receptor blockers like clonidine block stress and cue-induced craving for opioids and cocaine. To determine whether clonidine can reduce lapse and relapse, researchers conducted a randomized double blind placebo-controlled clinical trial of clonidine up to 0.3 mg once daily for 12 weeks among 118 research volunteers with opioid use disorder who had been abstinent for 5 weeks receiving buprenorphine maintenance with daily dispensing from a research clinic. Urine tests for opioids and cocaine were done 3 times weekly. Lapse was defined as any positive or missed urine test and relapse was defined as ≥ 2 consecutive lapses. Ecological momentary assessments (EMA) were collected via handheld devices to determine whether stress was decoupled from craving as a mechanism by which clonidine may reduce lapse and relapse.

• Time to opioid lapse was reduced for the clonidine group with a hazard ratio of 0.67, compared with the placebo group. This effect was attributable to the subgroups with no or low cocaine use and not the groups with high cocaine use, whose participants were more likely to experience a lapse.
• Time to relapse was reduced in the clonidine group.
• The clonidine group had more days of continuous opioid abstinence than the placebo group (35 versus 26 days) by urine drug testing, but no difference in overall percentage of opioid negative urine tests (89% versus 80%).
• In the EMA analysis, clonidine reduced the likelihood of heroin cravings overall and there was a decoupling of stress from craving in the clonidine group.
• The clonidine group was more likely to have adverse events than the placebo group (95% versus 84%). Dry mouth, sedation, and hypotension were more common in the clonidine group.

Comments:

Clonidine is an anti-hypertensive medication that is frequently prescribed off-label for anxiety and opioid withdrawal. It is also commonly diverted to enhance the effects of opioids. This study found some evidence that clonidine can be useful as an adjunct to buprenorphine maintenance to reduce opioid lapses and that it reduces opioid craving, but the contexts in which its benefits outweigh its risks in real world clinical practice remain to be determined.

Alexander Y. Walley, MD, MSc

Reference:

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;172(8):760–767.