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Randomized Controlled Trial
. 2014 Feb;348(2):217-26.
doi: 10.1124/jpet.113.209478. Epub 2013 Nov 13.

A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine

D Andrew Tompkins  1 , Michael T Smith, Miriam Z Mintzer, Claudia M Campbell, Eric C Strain
Affiliations
Randomized Controlled Trial

A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine

D Andrew Tompkins et al. J Pharmacol Exp Ther. 2014 Feb.

Abstract

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

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Figures

Fig. 1.
Fig. 1.
Experimental design.
Fig. 2.
Fig. 2.
Mean Peak Daily Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS) ratings (± S.E.M.) during and after active drug cessation.
Fig. 3.
Fig. 3.
Mean Peak Daily Profile of Mood States (POMS) and Visual Analog Scale (VAS) ratings (± S.E.M.) during and after active drug cessation.
Fig. 4.
Fig. 4.
Mean peak daily physiologic measurements (± S.E.M.) during and after active drug cessation. (A) Pupil diameter. (B) Blood pressure. (C) Heart rate.
Fig. 5.
Fig. 5.
Mean peak number of concomitant medications (con meds; ±S.E.M.) for the treatment of withdrawal symptoms during and after active drug cessation.
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