Clonidine maintenance prolongs opioid abstinence

  • Despite effective treatments of opioid addiction, like buprenorphine and methadone, patients still relapse.
  • Episodes of craving leading to brief lapses or total relapse can be triggered by stress, exposure to drug-associated cues, or the use of an initially small amount of drug.
  • Buprenorphine maintenance, therefore, might be improved with the addition of a treatment that specifically buffers the effects of one or more of those triggers. 

A study reported in the American Journal of Psychiatry reported on whether clonidine blocks stress-induced seeking of heroin and cocaine. This study was not performed in the Clinical Trials Network, but involved a researcher from the Center for the Clinical Trials Network and is relevant to the CTNs Opioid Research Task Force.

To find out if clonidine might work in that role, researchers conducted a randomized, double-blind, placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic.  

The 118 participants (57%) who achieved 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 three times per week, with "lapse" defined as any opioid-positive or missed urine test, and "relapse" defined as two or more consecutive lapses.

Analysis found that clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase.  There was no difference between clonidine and placebo groups in time to relapse, but those in the clonidine group took longer to lapse.  Assessment showed that the impact of daily life stress on opioid craving was partly mitigated in the clonidine group.

Conclusions:  Clonidine, a readily available medication, is useful in opioid dependence treatment not just for reduction of withdrawal signs, but also as an added maintenance treatment that increases duration of abstinence.  Even in the absence of physical withdrawal, it appears to help decouple stress from craving in everyday life, making it a potentially valuable tool in maintaining abstinence for those in recovery.

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.

Articles were written based on the following published research:

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;172(8):760-767. doi: 10.1176/appi.ajp.2014.14081014