Buprenorphine May Beat Opioids for Triad of Pain, PTSD, SUDs

Kenneth Bender

March 08, 2016

Buprenorphine (multiple brands) may be superior to opioids in the treatment of veterans with the difficult triad of chronic pain, posttraumatic stress disorder (PTSD), and substance use disorders (SUDs), new research shows.

In a retrospective cohort study, investigators found that twice as many veterans treated with the partial nociceptin opioid receptor agonist experienced improvement in PTSD symptoms, beginning at 8 months and increasing over time. In contrast, those treated with opioids experienced a worsening of symptoms.

"This positive effect on PTSD symptoms, although modest, increased with increasing time on buprenorphine without an increase in pain. In contrast, there was a nonsignificant trend toward worsening of PTSD symptoms with more time on opioid therapy," the authors, led by Karen Seal, MD, MPH, San Francisco Veterans Affairs Medical Center and the University of California, San Francisco, write.

"We rarely see patients who have isolated, chronic pain; and, for that matter we rarely see patients who have isolated PTSD or isolated opioid use disorder," Dr Seal told Medscape Medical News.

"It's sometimes very hard to get avoidant patients ― and patients who have PTSD are naturally avoidant ― it's hard to help these patients engage in care. When you have a single medication or a single treatment that can actually address several different components of what they're suffering from, it's often easier to get them engaged," she said.

The study was published online March 1 in the Journal of Clinical Psychiatry.

Search for a Single Treatment

The investigators note that among an estimated half million US veterans who served in Iraq and Afghanistan and who received a diagnosis of chronic pain, those with PTSD were significantly more likely to receive prescriptions for opioids, to misuse these medications, and to have a higher risk for adverse clinical outcomes, such as overdose, injuries, and suicide.

Although the investigators found no single, evidence-based treatment for the co-occurring conditions of chronic pain, PTSD, and SUDs, they were intrigued by the possibility that the unique pharmacology of buprenorphine may make it an effective treatment for PTSD, in addition to its approved use as a substitute for more addictive opioid analgesics in substance use disorder.

They suggest, for example, that acting as an antagonist at the kappa-opioid receptor could exert an antidepressant effect that would be of benefit for patients with co-occurring PTSD. However, beyond a single case report, no published studies have supported this hypothesis.

"There was nothing, nothing in the literature to guide us in the use of buprenorphine in these patients who have all three problems. Yet these veterans who have all three problems are quite common in our system, and these patients are really common in the community, so I was really excited to do this work," said Dr Seal.

The exploratory, observational, retrospective study included 382 veterans of the Iraq and Afghanistan wars who were diagnosed with chronic, comorbid pain, PTSD, and SUDs. The study's primary outcome measure was change in PTSD symptoms, as measured by the VA Primary Care PTSD Screen and/or the PTSD Checklist, among veterans who received sublingual buprenorphine (n = 177) in comparison with those maintained on moderately high-dose opioid therapy (n = 205).

Results showed that twice as many veterans (23.7%) in the buprenorphine group experienced significant improvement in PTSD symptoms compared with those the opioid group (11.7%).

"Compared to veterans in the opioid therapy group, veterans receiving buprenorphine showed significant improvement in PTSD symptoms after 8 months, with increasing improvement up to 24 months (incidence rate ratio = 1.79; 95% confidence interval, 1.16 - 2.77; P = .009). There were no differences in the longitudinal course of pain ratings between groups," the investigators report.

Although encouraged by the findings, Dr Seal cautioned that prospective, randomized controlled trials are necessary to confirm these findings.

"There is a signal that buprenorphine may actually lead to improvement in PTSD symptoms, but we really don't know how this would translate into real patients in a clinical setting or in a trial," she said.

However, Dr Seal is optimistic that the drug may have utility beyond the research setting and in other populations, such as women with this triple diagnosis.

"There would not necessarily be a reason to suspect that buprenorphine would act differently in women and men," Dr Seal said. "Buprenorphine is actually widely used in the community for the treatment of opioid use disorder in both women and men, and I don't think that different gender effects or differences by gender are reported."

Beyond the Research Setting

Commenting on the study for Medscape Medical News, Babak Tofighi, MD, clinical assistant professor of population health, New York University Langone Medical Center, in New York City, shares the hope that buprenorphine will prove to be effective beyond the research setting.

Dr Tofighi told Medscape Medical News that the current study by Dr Seal and colleagues not only explores a novel treatment approach for veterans suffering from the debilitating triad of chronic PTSD, pain, and opioid use but also "sheds light on buprenorphine's possible link to reducing anxiety and depression."

However, he agreed that additional prospective research is necessary to fully assess the effect of buprenorphine in real-world settings.

The investigators and Dr Tofighi report no relevant financial relationships.

J Clin Psychiatry. Published online March 1, 2016. Abstract


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