Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: Chronic use of opioids for management of back pain is controversial and hotly debated. This randomized trial showed no benefit of opioids over multimodality non-opioid treatments, consistent with many other observational studies.

SOURCE: Krebs EE, Gravely M, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain. JAMA 2018;319:872-882.

Traditionally, chronic low back pain is treated with nonsteroidal anti-inflammatory agents, tricyclic antidepressants, antiepileptic drugs, and serotonin/
norepinephrine reuptake inhibitors. Epidural steroid injections also may be offered, but long-term benefit, lasting six months or longer, is not appreciated. Opioids are often administered, but no randomized trials comparing opioids to placebo are available to evaluate opioid long-term effectiveness or safety. Are long-term opioids better than non-opioid medications in the management of moderate to severe chronic back pain?

To address this question, a 12-month, randomized trial with masked outcome assessment, the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial, was performed through 62 Minneapolis Veteran Affairs primary clinics from June 2013 to December 2016. Patients who, despite analgesic use, experienced chronic back pain or hip or knee osteoarthritic pain were included if they had moderate to severe pain nearly every day for at least six months or more, with moderate to severe pain defined as a score of ≥ 5 on the three-item pain intensity, interference with enjoyment of life, and interference with general activity (PEG) scale (range, 0 to 10). Patients already on long-term opioid therapy, or whose life expectancy was less than 12 months, were excluded. Both opioid and non-opioid medication groups followed a treatment strategy to improve pain and function in three steps. Immediate-release (IR) opioids were administered to the opioid group, starting with morphine IR, hydrocodone/acetaminophen, or oxycodone IR. Step 2 offered morphine sustained-action (SA) or oxycodone SA, and Step 3, transdermal fentanyl. For the non-opioid group, acetaminophen or a nonsteroidal anti-inflammatory drug was the first step, with adjuvant oral medications added as Step 2, including nortriptyline, amitriptyline, gabapentin, or topical analgesics (i.e., capsaicin, lidocaine), and Step 3 included drugs requiring prior VA clinic authorization, such as pregabalin, duloxetine, or tramadol. Medications in both groups were adjusted per individual patient response.

Pain-related function was the primary outcome measure, as measured by the seven-item Brief Pain Inventory (BPI) interference scale, whereas secondary outcome measures comprised several questionnaires, including, among others, the Veterans RAND 12-item Health Survey quality-of-life measure, the 11-item Roland-Morris Disability Questionnaire measure of pain-related physical function, and the eight-Item Patient Health Questionnaire depression measure. Statistical analysis comprised the two-sided t tests and χ2 tests, with a P value < 0.05 considered statistically significant.

Among 275 patients enrolled, 240 were randomized, with excellent follow-up rates, 92% at three months, 97% at six months, 90% at nine months, and 98% at 12 months. Mean age was 58.3 years, 65% (n = 156) had back pain, 35% had hip or knee osteoarthritis pain, and 13% were women. No significant difference in pain-related function or health-related quality of life was found between the two groups over 12 months, whereas pain intensity was significantly better in the non-opioid group, and the opioid group had significantly more medication-related symptoms. Opioids are not superior to non-opioids for moderate to severe chronic back pain and their use cannot be supported.

COMMENTARY

Based on the National Health Statistics Report from the Centers for Disease Control and Prevention, low back pain is the most common condition for which patients seek complementary and alternative medicine care — and for good reason. Despite a 629% increase in Medicare expenditures for epidural steroid injections, a 423% increase in expenditures for opioids for back pain, a 307% increase in the number of lumbar magnetic resonance images among Medicare beneficiaries, and a 220% increase in spinal fusion surgery rates, no population-level improvements in patient outcomes, disability rates, or reduction in morbidity of low back pain have been appreciated. Alternative methods of alleviating chronic low back pain are needed, and limiting, if not eliminating, opioid use would seem to be a step in the right direction.