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The extended-release formulation of the mild opiate tramadol may keep patients in "detox" and suppress withdrawal symptoms, researchers found.

In a randomized controlled trial, more participants completed a week-long opioid taper if they were on buprenorphine compared with clonidine (90% versus 66%, P=0.01), and retention with tramadol didn't differ significantly between groups (72%), reported Kelly Dunn, PhD, of Johns Hopkins in Baltimore, and colleagues in .

The researchers interpreted that finding as tramadol producing similar retention to buprenorphine, and potentially being a good stand-in, to overcome the potential problems of abuse liability with buprenorphine and sedative effects with clonidine.

But Dunn warned that while the study "provides strong support for the use of tramadol ER for supervised opioid withdrawal settings, it is not a definitive evaluation and tramadol ER is not without its own risks. Therefore, the decision to use tramadol ER for this indication would have to be made on an individual provider basis."

She added that tramadol ER "may have particular value for settings in which buprenorphine is not available."

For patients with opioid use disorder, supervised withdrawal -- also known as "detoxification" -- is one treatment strategy, and buprenorphine and clonidine are commonly used. The challenge with buprenorphine is that it has abuse potential, and clonidine has low abuse liability but it has to be given several times a day and can produce sedation.

To assess whether the mild-to-moderate opioid agonist tramadol ER would be a better alternative, Dunn's group enrolled 103 participants from a residential research setting from Oct. 25, 2010 to June 23, 2015. The majority (85%) were men, 42% were white, and the mean age was 29.

All patients were first stabilized with 30 mg morphine four times daily, followed by a 7-day taper in which they were randomized to one of three drugs: clonidine, buprenorphine, or tramadol ER. Patients then crossed over to placebo during a post-taper period.

The tramadol dose could go as high as 600 mg/day -- far higher than the 300 mg/day recommended for chronic pain treatment -- which is appropriate for patients with high levels of opioid tolerance, the researchers noted.

Dunn's group found that tramadol generally produced better retention and withdrawal suppression than clonidine and was comparable to buprenorphine during the 7-day taper, and was associated with less severe withdrawal than buprenorphine in the post-taper period.

There was no difference in withdrawal between groups on observer-rated outcomes as measured by the Clinical Opiate Withdrawal Scale (COWS) score. However, patient-reported outcomes, as measured by the Subjective Opiate Withdrawal Scale (SOWS), showed significantly more severe withdrawal with clonidine versus tramadol and buprenorphine during the taper period in a post-hoc analysis.

After the taper period, patients on clonidine and tramadol reported significant reductions in withdrawal compared with those on buprenorphine, suggesting that those on this partial opioid agonist experienced withdrawal after being taken off the drug.

There was no difference in patients remaining enrolled on the final study day whether they were tapered with any of the three drugs, as 58% in each group stayed on until the end of the study.

Petros Levounis, MD, of Rutgers New Jersey Medical School, who was not involved in the study, challenged the study's focus on medical withdrawal, or "what we used to call 'detoxification,' which is not even effective treatment for opioid use disorder. In fact, in many cases it is quite dangerous. Medical withdrawal simply addresses the first 7 days of only one treatment: naltrexone. Neither methadone nor buprenorphine inductions use medical withdrawal."

Medication-assisted treatment (MAT), on the other hand, "addresses the actual illness of opioid use and is a matter of several months and often years," Levounis said. "Buprenorphine maintenance is a proven safe and effective treatment for opioid use disorder and should be used as the first-line treatment of the illness."

Dunn noted that withdrawal with tramadol can theoretically be used as a bridge to MAT, "though that has not been empirically established. But tramadol has mu [opioid] receptor activity, so therefore it would be reasonable to consider transitioning people from tramadol to methadone or buprenorphine."

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