New research shows effects of long-term use of opioid therapy

Half of patients on high-dose, long-term opioid therapy had hormonal disturbances or signs of inflammation, while 100 percent reported improved pain control and mental outlook, new research shows. The results, reported today at the 29th Annual Meeting of the American Academy of Pain Medicine, present rare data on the effects of opioids beyond 10 years. Most clinical trials that examine opioid use are of short duration, and little is known about long-term outcomes, particularly in patients who suffer from noncancer pain.

The 40 patients included in the study were evaluated between July and October 2012. Each had been taking a high dose of opioid therapy, defined as more than 100 mg equivalence of morphine a day, for 10 or more years. Each complained of constant, debilitating pain that was classified as intractable, which is defined in California as "incurable by any known means." They had tried many non-opioid methods to try to control their pain. Every patient in the study also suffered from severe insomnia.

The patients were tested for serum cortisol, pregnenolone, corticotropin (ACTH), testosterone, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
In addition, each patient took 2 written questionnaires. One measured improvements to 17 physiologic functions, including reading, hearing, concentration, memory, driving, sleep, movement, dressing and libido. The other questionnaire asked about depression, hopelessness and quality of life before and during opioid treatment.

All 40 patients reported improvements in depression, hopelessness and quality of life and sustained pain control that accompanied a stable opioid dosage. In addition, all patients reported improvements in at least 1 physiologic function. Categories in which at least 20 patients noted improvements were concentration (27 or 67.5 percent), walking (25 or 62.5 percent), appetite (20 or 50 percent) and movement (31 or 77.5 percent). Seventeen or 62.5 percent of patients reported improvements to sleeping.

Eight patients (20 percent) had hormonal suppression as follows: ACTH in 2 (5 percent), cortisol in 3 (7.5 percent), testosterone in 2 (5 percent) and pregnenolone in 4 (10 percent) of patients. Three patients (7.5 percent) had one or more serum elevations of a hormone as follows: ACTH in 1 (2.5 percent), cortisol in 2 (5 percent) and pregnenolone in 1 (2.5 percent). Nine patients (22.5 percent) had an elevated CRP or ESR.

"The high-dose opioid patients studied here greatly improved many physiologic functions and mental outlook," Forest Tennant, MD, PhD, study author and medical director of Veract Intractable Pain Clinic in West Covina, concluded, writing in a scientific poster. "Despite these improvements, 12 (30 percent) of patients had an elevated serum hormone level, an inflammatory marker, or both, suggesting the presence of an on-going painful, inflammatory process."

In addition, he wrote, the observed hormonal suppression was a significant complication.

Such findings are noteworthy as the U.S. Food and Drug Administration (FDA) and some states mull limits to opioid prescribing as a means to halt a rising tide of prescription drug abuse and overdose deaths. An FDA panel held a two-day public hearing in February to gather stakeholder testimony as it weighs labeling changes for opioid dosage, indication and treatment duration for noncancer pain.


American Academy of Pain Medicine


  1. Donna Garrett Donna Garrett United States says:

    I took hydrocodone for 20+ years for rheumatoid arthritis. This medicine made me a super women. But I began to get the ceiling effect on the medication. Now that I am not taking this medicine anymore I am a complete wreck. I can't hardly function. It has destroyed my life, my family everything. It has been 5 years since I have taken the medication. I am getting worse. I have developed sever bipolar symptoms. The medications I am on now I can't afford. I am desperate and will submit to any study anyone has on this planet. I had or have ADHD.  I am 53 years old and it's hard to see a future.

    • Russ Eiseman Russ Eiseman United States says: too, 66 year old DAV on opiate medication for 16 years and the VA took it away and i am a wreck future, about to become homeless as i cannot do the work involved living off-grid.  What can we do but try and survive?  be safe

  2. Dorsey Greene Dorsey Greene United States says:

    After a 29 year Army Career I had a lot of injuries and Sarcoidosis and 100% disability rating from the VA. I have been prescribed Opioids for pain for the last 15 years. I was started on Morphine then Fentanyl, Methadone and back to Fentanyl due to the Heart rythm elongation problem Methadone can cause. I had a Stress test done 2 years before at age 61 and results were my Heart was like a 19 year olds. I would like to get off Opioids but I don't know how I could live with the pain, I could not walk, sit or stand. I guess that I will be on Opioids till I die. If there is ever proof that Marijuana in some form would help with pain I would try it if I live in a State where it is legal.

  3. G Cavalli G Cavalli United States says:

    Thank you again Dr. Tennant for your work with pain patients.  I have a failed lumbar back fusion which caused CRPS in both my legs now, all due to military service. This was 17 years ago. I also have a fused cervical spine and an ankle with screws due to drop foot from the lumbar surgery.  I have been on opioid therapy for 17 years and I could not get out of bed without it. We thank you for continued work even through the harassment you have received by even working with us. We are so very thankful for all of your tireless efforts.
    Dr. G M. Cavalli

  4. Big K K Big K K United States says:

    So basically this article proves 100% that opioids are of HUGE benefit to those with Chronic Pain like me.  The “so called side effects” of long term use are really nothing more that side effects of the disease that said person has.  the headline for this article is 100% BS and should be changed.  The study proved nothing as far as long term issues with opioids.  I was on about 65mg a day and last bed a pretty darn normal life.  Then the FDA and CDC got their panties in a bunch and I have been put through the ringer since.  I am currently only given 40 mg a day with no extended release medication.  We all know that 12 hour opioids last 6-8 and immediate release last 2-4 not 4-6.  So my days now suck 100% and I have a 11 and 13 year old plus a great wife and I am becoming a burden because some stupid druggies ruined my life.    Leave us alone so we may be productive citizens other wise you will be paying me disability and who pays for that.  Seriously 20 to 50 dollars a month for my medication to live or you pay me 1,600 or so a month from taxpayers money.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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