Opioids unlikely to provide clinically meaningful reduction in chronic non-cancer pain

1. In this systematic review and meta-analysis of patients with chronic non-cancer pain, though opioids showed small improvements in pain, physical functioning, and sleep quality, these differences did not meet minimally important standards and diminished with longer follow-up.

2. There was no difference in pain or physical functioning for opioids compared to NSAIDs or tricyclic antidepressants

Evidence Rating Level: 1 (Excellent)

Study Rundown: Though opioids are an important treatment for acute and extreme pain, especially post-surgically, their use in treating chronic pain has fallen under scrutiny. As the dangers of opioid overprescribing are increasingly being realized, understanding when opioids are likely to be effective is essential. In this systematic review and meta-analysis of patients with chronic non-cancer pain, opioids were associated with small improvements in pain, physical functioning, and sleep quality compared to placebo. However, these differences did not meet minimally important standards, and there were no differences in emotional, social, or role functioning. Importantly, opioids did not improve pain or physical functioning compared to NSAIDs or tricyclic antidepressants. Opioids were associated with a higher rate of side effects, especially vomiting.

This study suggests that opioids are of minimal benefit for chronic pain, likely diminish in effectiveness with prescription length, and do not outperform safer options for non-cancer chronic pain treatment. Though the evidence in this study was well-compiled and analyzed, there remains some limitations. Most notably, this study was restricted to patients without co-morbid substance use or mental health disorders, making generalizability to an average clinical population difficult. In addition, the longest follow-up of surveyed studies was 6 months, and so the longer-term effects of opioid use for chronic pain are still unclear.

Click to read the study in JAMA

Relevant Reading: The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

In-Depth [systematic review and meta-analysis]: 96 trials including 26,169 patients were included after meeting eligibility criteria, consisting of patients with chronic non-cancer pain, randomized to opioid versus non-opioid control, and follow-up for at least 4 weeks. Pain intensity was converted to the 10 cm Visual Analog Scale (VAS) for pain, sleep quality to the 100mm VAS for sleep, and physical, emotional, and social functioning to the 100-point 36-item short form survey (SF-36). The median age was 58 years (IQR 51-61 years), 61% female, with a mean pain score of 6.54 cm on the VAS. While all trials were at risk for bias, 51% had adequate randomization, 50% appropriately concealed allocation, and >85% blinded study participants and clinicians. Though opioids were found in improve pain (weighted mean difference -0.79 cm; CI₉₅ -0.90 to -0.68 cm), physical functioning (weighted mean difference 2.04 points; CI₉₅ 1.41 to 2.68 points), and sleep quality (weighted mean difference 4.56 mm; CI₉₅ 2.88 to 6.24 mm), they did not reach the minimally important differences. In addition, studies with longer follow-up had less pain relief (p = 0.04 for interaction). There were no statistical differences found for emotional, social, or role functioning (p > 0.05). Opioids did not show differences in pain improvement compared to NSAIDs and tricyclic antidepressants (p > 0.05), though they did show a small difference compared to anticonvulsants (weighted mean difference -0.90 cm; CI₉₅ -1.65 to -0.14 cm).

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