Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: A randomized controlled trial with ecological momentary assessment

William J. Kowalczyk, Karran A. Phillips, Michelle L. Jobes, Ashley P. Kennedy, Udi E. Ghitza, Daniel A. Agage, John P. Schmittner, David H. Epstein, Kenzie L. Preston

Research output: Contribution to journalArticlepeer-review

Abstract

Objective:Theauthors testedwhetherclonidineblocks stressinduced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. Method: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo(N=57) for 14weeks. Urine was tested thrice weekly. Lapse was defined as any opioidpositive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined withCoxregressions;longestperiodofabstinencewasexamined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. Results: In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] comparedwith25.5days [SD=2.7];Cohen'sd=0.38).Therewas no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. Conclusions: Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also asan adjunctivemaintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Original languageEnglish (US)
Pages (from-to)760-767
Number of pages8
JournalAmerican Journal of Psychiatry
Volume172
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Psychiatry and Mental health

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