Tramadol comparable to buprenorphine in reducing opioid withdrawal symptoms

By Joan Stephenson

NEW YORK (Reuters Health) - Extended-release tramadol (tramadol ER) is as effective as buprenorphine and more effective than clonidine in reducing withdrawal symptoms during medically supervised “detox” in patients with opioid use disorder (OUD), new research suggests.

“Supervised opioid withdrawal . . . has particular value in settings where agonist maintenance treatments are already at capacity or not available for other reasons,” first author Dr. Kelly E. Dunn, of Johns Hopkins University School of Medicine in Baltimore, Maryland, told Reuters Health by email.

Medically supervised withdrawal, the most widely accessed treatment for OUD, is managed primarily with clonidine or buprenorphine. Both drugs have drawbacks, Dr. Dunn said.

“Clonidine produces low-magnitude effects and requires multiple daily dosing (which is subject to problems with adherence), and buprenorphine is more effective but has logistical/legal barriers that prevent it from being used in all settings,” she explained.

The mild to moderate opioid agonist tramadol hydrochloride ER “activates the same receptor system as buprenorphine (suggesting it would be more effective than clonidine), and it may be more easily prescribed or accepted in areas where buprenorphine is not available,” she said.

The 26- to 28-day randomized trial involved 103 participants (85% men, mean age about 29) in a residential research setting, recruited from 2010 to 2015.

After a morphine “stabilization” phase of seven to 10 days, during which participants were given subcutaneous injections of 30 mg morphine four times daily, they were randomized to receive clonidine, buprenorphine, or tramadol ER during a seven-day taper phase. Patients were then given placebo capsules or tablets during a seven-day post-taper period.

Tramadol ER resulted in retention in treatment and withdrawal suppression “greater than clonidine and comparable to buprenorphine during the 7-day taper and was associated with less severe withdrawal symptoms relative to buprenorphine in the post-taper period,” the researchers report in JAMA Psychiatry, online July 12.

Retention rates at the end of the taper were 72% for tramadol, 90% for buprenorphine, and 61% for clonidine. Buprenorphine recipients were significantly more likely than clonidine recipients to be retained (p=0.01); retention among the buprenorphine and tramadol groups did not differ significantly.

Retention rates on the last day of the study were 58% for all three groups.

Although there was no difference in withdrawal symptoms between groups as rated by study staff using the Clinical Opioid Withdrawal Scale (COWS), participant-reported Subjective Opiate Withdrawal Scale (SOWS) scores showed significantly more severe withdrawal symptoms in a post-hoc analysis for clonidine compared with tramadol (p=0.02) and buprenorphine (p

In the post-taper phase, symptoms among those who had received clonidine or tramadol decreased significantly, but those who had received buprenorphine had a slight increase in withdrawal symptoms, suggesting they continued to experience withdrawal following the removal of the drug, the researchers noted.

Although existing methods to treat opioid withdrawal are generally not very effective, “it is imperative that the field continue working to improve outcomes from these treatments because they make additional forms of care available for patients with opioid use disorder,” Dr. Dunn said.

“The rigorousness of the study may limit its real-world applicability,” Dr. Andrew J. Saxon, of the University of Washington and director of the Center of Excellence in Substance Abuse Treatment and Education for the VA Puget Sound Health Care System, in Seattle, told Reuters Health by email.

A “real-world” comparison would have omitted the week of morphine stabilization because most patients “typically are admitted with imminent withdrawal that must be addressed immediately,” he said.

Dr. Saxon, who was not involved with the study, said relapse occurs among most patients who undergo supervised opioid withdrawal, and they are at heightened risk for overdose and death after recent withdrawal because their tolerance is lowered.

Currently, the optimal treatment for opioid use disorder is not withdrawal but long-term treatment with naltrexone (which requires complete withdrawal), or with methadone or buprenorphine (which can be started without the need for complete withdrawal), he explained.

“Thus, in 2017 the only value of withdrawing a patient from opioids is to place the patient on naltrexone,” Dr. Saxon said.

Only 18 of the 103 study participants voluntarily started naltrexone. Although tramadol was as effective as other medications in achieving this outcome, it also has no obvious advantages, he said.

The most important point elucidated by the study is that if resources continue to be used for medically supervised withdrawal, better strategies are needed to ensure that patients are on naltrexone, preferably long-acting injectable naltrexone, at the end of the withdrawal episode, he said.

Buprenorphine and placebo were provided by an unrestricted grant from Reckitt Benckiser Pharmaceuticals.

SOURCE: https://bit.ly/2tEQVzC

JAMA Psychiatry 2017.