Less Pain but Hormonal Effects With Long-Term Opioid Use

Fort Lauderdale, Florida — Patients with chronic pain who have been taking opioids for upwards of a decade report good pain control and quality of life, but almost a third of them have a worrisome increase in hormonal or inflammatory markers, a new study shows.

"What that means is that for a lot of these people their quality of life, their mental outlook, their depression have gone, and physiologically, they are also better, many being able to work and function quite well," the study's author, Forest Tennant, MD, PhD, Veract Intractable Pain Clinic, West Covina, California, told Medscape Medical News.

"What was a little tragic is that these people still have an underlying inflammatory disease that is not taken away by opioids or anything else."

Dr. Tennant believes that the neuroinflammation is due to centralized pain and that an underlying disease, such as fibromyalgia or lupus, could be a root cause.

The results were presented here at the American Academy of Pain Medicine (AAPM) 29th Annual Meeting.

Intractable Pain

The study included 40 patients, aged 30 to 65 years, 60% female, who had been receiving high doses of opioids ( > 100 mg equivalence of morphine a day) for 10 years or longer. Some patients were taking much higher doses, as high as 1000 mg a day, said Dr. Tennant, who has been treating pain patients since the 1970s.

Dr. Forest Tennant

Tests have revealed that about 85% of these patients have a genetic metabolic defect in opioid metabolism, added Dr. Tennant. "These people are totally tolerant."

Patients all met the California definition of intractable pain, which is "incurable by any known means." All had tried multiple nonopioid therapies before opioid treatment, and all had constant, debilitating pain with severe insomnia.

About 65% of the patients have a spine-related condition, either cervical or lumbar. Most of the other third had such conditions as head trauma, rare genetic disorders, and autoimmune inflammatory diseases, said Dr. Tennant.

Patients completed a questionnaire on physiologic functions and another on depression, hopelessness, and quality of life. Dr. Tennant tested serum cortisol, pregnenolone, corticotropin (adrenocorticotropin-releasing hormone), testosterone, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).

All 40 patients reported sustained pain control on a stable opioid dosage. All also reported improvements in depression, hopelessness, and quality of life and in one or more physiologic functions, such as reading (42.5%), hearing (25.0%), concentration (67.5%), walking (62.5%), appetite (50.0%), sleeping (62.5%), movement (77.5%), and libido (40.0%).

But hormonal suppression was a significant complication in 20.0% of the patients. These included deficiencies in ACTH (5.0%), cortisol (7.5%), testosterone (5.0%), and pregnenolone (10.0%).

Dr. Tennant believes the endocrine deficiencies were even higher than those captured in the study. "I'm going to guess that about half of these subjects have endocrine suppression and half don't, but in the poster it only showed up at about 20% because we didn't take a good history on how many people were taking estrogen," he noted, or obtaining it from other products from health food stores or other sources.

As well, researchers found 1 or more serum elevations of a hormone in 7.5% of patients: ACTH (2.5%), cortisol (5.0%), and pregnenolone (2.5%). Also, 22.5% of the patients had an elevated CRP level or ESR.

Dr. Tennant is convinced that some of those patients could have underlying lupus or fibromyalgia or some other condition. "What this shows is that these people are being symptomatically cared for, but we're not curing some of them."

"Feverish Debate" on Opioid Use

According to Dr. Tennant, these long-term opioid users have gotten something of a bad rap recently with the "feverish" debate over cracking down on prescription opioid misuse. Diabetes patients taking insulin or heart patients taking digitalis don't get the same scrutiny. "There is not a single person in this group who wants to take these drugs," he said.

He's keen to defend these opioid users, stressing that they have tried "everything else," were once bed bound or house bound and totally debilitated, and now can function. "Centralized pain is not curable," he said. "People die from this type of intractable and centralized pain if they don't get help, and if they're functioning and they're doing well, is there a problem here?"

Dr. Tennant now plans to perform the same evaluation on patients who have been receiving opioids even longer — 20 and 30 years — and may add other measures, such as liver function testing and blood counts. Asked to comment on this study, Lynn Webster, MD, medical director, CRI Lifetree, Salt Lake City, Utah, and new president of the AAPM, said the study goes a long way toward filling the gap of missing long-term efficacy data on opioid use.

"There's very little out there that investigates long-term opioid use," said Dr. Webster. "Long term is what, anything more than 12 weeks or a year? This is 10 years and 10 years is a long time and if people can maintain efficacy for 10 years then it is addressing that question of whether chronic opioid therapy can be effective."

He noted that the study uncovered potential endocrine adverse effects, which are well known in this population. "But despite that, after 10 years of therapy people maintain reasonable efficacy from the opioids."

The authors have disclose no relevant financial relationships.

American Academy of Pain Medicine (AAPM) 29th Annual Meeting. Poster 135. Presented April 11, 2013.