Tramadol HCl extended-release (ER) proved to be more effective than clonidine and was comparable to buprenorphine in reducing opioid withdrawal symptoms during a supervised tapering program, according to findings published in JAMA Psychiatry.

In patients with opioid use disorder (OUD), clonidine or buprenorphine HCl are commonly used during supervised withdrawal (eg, detoxification) from opioids. Tramadol ER is an analgesic possessing both opioid and non-opioid mechanisms with low abuse potential. Kelley E. Dunn, PhD, and colleagues from Johns Hopkins University School of Medicine, Baltimore, MD, aimed to evaluate if tramadol ER was effective when used in these withdrawal environments. 

The researchers conducted a randomized trial (n=103) in a residential research setting of patients with OUD stabilized on subcutaneous (SC) morphine 30mg given 4 times daily. In the study, patients were tapered over 7 days using clonidine, tramadol ER, or buprenorphine, and later crossed over to double-blind placebo during a post-taper period. 

The main outcomes were retention, management of withdrawal symptoms, concomitant drug utilization, and naltrexone induction. 

The data showed patients receiving buprenorphine (90.3%) were significantly more likely to be retained at the end of the taper vs. patients receiving clonidine (66.1%)  but retention with tramadol ER (72.2%) was moderate and did not significantly differ from that of the other treatment arms (P=0.01). Analyses of the Subjective Opiate Withdrawal Scale (SOWS) total scores indicated significant reductions in withdrawal severity between the taper vs. post-taper phases for clonidine (13.1 vs. 3.2; P<0.001) and for tramadol ER (7.4 vs. 2.8; P=0.03). A significant reduction was not seen, however, for buprenorphine (6.4 vs. 7.4). 

Compared with the stabilization phase, concomitant drug use increased significantly in both the clonidine (P<0.001) and tramadol ER (P=0.003) groups during the taper phase, while patients in the buprenorphine group used significantly more drugs during the post-taper phase (P=0.006)  Moreover, the authors did not find a significant difference in the proportion of patients choosing naltrexone therapy among the three arms: clonidine (22.2%), tramadol ER (9.4%), and buprenorphine (9.7%). 

The findings “support further examination of tramadol ER as a method to manage opioid withdrawal symptoms,” the authors concluded.

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