Evidence ‘Insufficient’ to Support Antidepressant Use for Chronic Pain

Antidepressants are often prescribed for treating chronic pain. However, there is insufficient evidence attesting to their efficacy for pain relief, according to a Cochrane review published earlier this year. After conducting a meta-analysis of 176 studies involving 28,664 patients, the Cochrane researchers concluded that only duloxetine was moderately effective for the treatment of chronic pain.

“What became evident was the poor quality of much of the evidence. Trials were often very small, reports of adverse events were scarce, and there were almost no long-term follow-ups beyond the end of the interventions,” senior author Tamar Pincus, Ph.D., M.Phil., M.Sc., told Psychiatric News. She is the dean of faculty of environmental and life sciences and a professor of health psychology at the University of Southampton in the United Kingdom. “Several antidepressants were very commonly used and were recommended by several guidelines, but the evidence for their effectiveness was very poor.”

The meta-analysis included randomized, controlled trials with an average length of 10 weeks. Eighty-three of the studies were placebo-controlled, and 141 of the studies were parallel-armed.

The most common pain conditions examined were fibromyalgia; neuropathic pain; and musculoskeletal pain, such as osteoarthritis or back pain. The most common antidepressant classes investigated were serotonin-noradrenaline reuptake inhibitors, tricyclic antidepressants, and selective serotonin reuptake inhibitors. The most common antidepressants investigated were amitriptyline, duloxetine, and milnacipran. Of the 146 studies that reported where their funding came from, pharmaceutical companies funded 72 studies. Overall, most of the studies excluded patients who had low mood, depression, or other mental health conditions.

The standard dose of duloxetine, 60 mg, showed a small to moderate effect for substantial pain relief. The researchers noted that for every 1,000 people taking the standard dose, 435 will experience 50% pain relief compared with 287 who will experience 50% pain relief taking placebo.

“We did find moderate but consistent evidence for the efficacy of duloxetine in reducing pain and improving well-being across three large groups of chronic pain—fibromyalgia, musculoskeletal pain including osteoarthritis, and neuropathic pain,” Pincus said. She added that it would “make sense” for health professionals who are seeking to improve outcomes in patients with these conditions to prioritize duloxetine when they consider prescribing an antidepressant.

The researchers wrote that the standard 100 mg dose of milnacipran showed a “small effect” for pain intensity. However, they added that they were “not as confident in this result as [with] duloxetine because there were fewer studies with fewer people involved.”

The results of the meta-analysis suggest that 30 mg of mirtazapine had a moderate effect on mood, and duloxetine showed a small effect on mood, with the caveat that most studies excluded participants with mental health conditions and average anxiety and depression scores tended to be in the normal or subclinical range at baseline. Furthermore, excluding people with depression from most studies meant that there was no way for the Cochrane researchers to ascertain how effective antidepressants are for people with both chronic pain and depression.

“We remain in urgent need of large, methodologically sound, randomized, controlled trials on almost all antidepressants. These should have reasonable follow-up and include careful consideration of withdrawal monitoring,” Pincus said.

This meta-analysis was supported by the National Institute for Health and Care Research. ■