Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From
Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary
Assessment.
Author(s): Kowalczyk WJ(1), Phillips KA(1), Jobes ML(1), Kennedy AP(1), Ghitza UE(1), Agage
DA(1), Schmittner JP(1), Epstein DH(1), Preston KL(1).
Affiliation(s): Author information:
(1)From the Clinical Pharmacology and Therapeutics Research Branch, NIDA,
Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH,
Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and
Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Publication date & source: 2015, Am J Psychiatry. , 172(8):760-7
OBJECTIVE: The authors tested whether clonidine blocks stress-induced 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 14 weeks. Urine was tested thrice weekly. Lapse was defined
as any opioid-positive or missed urine test, and relapse as two or more
consecutive lapses. Time to lapse and relapse were examined with Cox regressions;
longest period of abstinence was examined 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] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was
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 as an adjunctive
maintenance treatment that increases duration of abstinence. Even in the absence
of physical withdrawal, it decouples stress from craving in everyday life.
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