Is Pain Treated Effectively With Antidepressants?

While some antidepressant drugs were effective for certain pain conditions, most were either ineffective or evidence was inconclusive, a review found.

Evidence of efficacy of antidepressants for pain emerged in 11 of 42 comparisons included in an overview of systematic reviews, reported Giovanni Ferreira, PhD, of the University of Sydney, and colleagues.

In four of these comparisons where antidepressants showed efficacy, evidence was of moderate certainty. They involved serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain, postoperative pain, fibromyalgia, and neuropathic pain, they wrote in The BMJ.

For the other 31 comparisons, antidepressants either were not efficacious or evidence was inconclusive.

Recent data have suggested that chronic pain is the most common condition leading to new antidepressant use among older adults in the U.S., U.K., Canada, and Taiwan — even more than depression, the researchers noted.

“Recommending a list of antidepressants without careful consideration of the evidence for each of those antidepressants for different pain conditions may mislead clinicians and patients into thinking that all antidepressants have the same effectiveness for pain conditions,” Ferreira said in a statement. “We showed that is not the case.”

“Some pain medicines may have a role in pain management, but they need to be considered as only part of the solution,” he added. “For some pain conditions, exercise, physiotherapy, and lifestyle changes may also help.”

Many of these lifestyle changes and treatments, including antidepressants, are recommended in the new CDC clinical practice guideline on opioids for pain.

The findings suggest that “for most adults living with chronic pain, antidepressant treatment will be disappointing,” noted Cathy Stannard, MBChB, of the National Health Service (NHS) Gloucestershire Integrated Care Board in Gloucester, England, and Colin Wilkinson, a lay member of the pain consortium at the University of Bath, England.

“This is important given emerging concerns about increases in the prescribing of antidepressants and the challenges patients describe when trying to withdraw from treatment,” Stannard and Wilkinson observed in an accompanying editorial.

“For people with pain, compassionate and consistent relationships with clinicians remain the foundations of successful care,” they pointed out.

“Research shows that what people want most is a strong, empathic relationship with their care provider,” the editorialists continued. “They want time to discuss what matters to them and they want easy access to support. Shared decisions and personalized care are fundamental to the successful support of people in today’s healthcare landscape.”

Ferreira and colleagues searched databases for systematic reviews comparing any antidepressant with placebo for any pain condition in adults. They found 26 reviews published between 2012 and 2022 spanning 156 trials and over 25,000 participants.

Those reviews reported on eight classes of antidepressants covering 22 pain conditions, with 42 antidepressant versus placebo comparisons. Industry ties were present in 45% of the reviews, absent in 29%, and unclear in 26%.

The main outcome was pain, except for headache disorders where it was headache frequency. The researchers converted continuous outcomes to a scale of 0 (no pain) to 100 (worst pain) and presented findings as mean differences. Dichotomous outcomes were presented as risk ratios (RR).

No review provided high certainty evidence about the effectiveness of antidepressants for pain for any condition.

Four reviews showed moderate certainty evidence for SNRIs including back pain (mean difference -5.3, 95% CI -7.3 to -3.3), postoperative pain (mean difference -7.3, 95% CI -12.9 to -1.7), neuropathic pain (mean difference -6.8, 95% CI -8.7 to -4.8), and fibromyalgia (RR 1.4, 95% CI 1.3-1.6).

Low certainty evidence suggested SNRIs were effective for pain linked with breast cancer treatment, knee osteoarthritis, and depression with comorbid pain. Low certainty evidence also suggested that selective serotonin reuptake inhibitors (SSRIs) were effective for depression and comorbid pain, and that tricyclic antidepressants were effective for irritable bowel syndrome, neuropathic pain, and chronic tension-type headache.

“We purposefully chose not to make judgments about the clinical importance of observed effects for each condition because commonly used thresholds, such as the 10-point reduction on a 0-100 scale commonly used in musculoskeletal pain research, are arbitrary, context specific (specific condition, treatment, comparison, and outcome), and potentially misleading if interpreted inappropriately,” Ferreira and colleagues noted.

“Given the challenges of making judgment calls about the clinical relevance of treatment effects, we encourage clinicians first to conduct a holistic assessment of the evidence, which includes an appraisal of the effect size, certainty of available evidence, and trade-offs between benefits and harms of each antidepressant, and then to involve patients in these discussions,” they added.