Some antidepressants are effective in treating chronic pain, but most lack evidence

Most antidepressants were either ineffective or lacked evidence for effectiveness when used for the treatment of certain chronic pain conditions, suggesting “a more nuanced approach is needed,” researchers wrote in BMJ.

According to Giovanni E. Ferreira, PhD, a research fellow at the University of Sydney’s Institute of Musculoskeletal Health, and colleagues, antidepressant use has increased in multiple countries for the treatment of chronic pain conditions, where management is often “suboptimal.”

“Among older people, recent data from Canada, the United States, the United Kingdom, and Taiwan suggest that chronic pain was the most common condition leading to an antidepressant prescription — even more so than for depression,” they wrote.

The researchers conducted an overview of systematic reviews to determine the safety, tolerability and effectiveness of several antidepressant treatment regimens for pain.

“Given the heterogeneity in the types of pain conditions for which the efficacy of antidepressants has been documented by existing systematic reviews, we chose to conduct an overview of systematic reviews to appraise efficacy estimates for each condition individually,” they wrote.

The researchers examined 26 reviews, which covered 22 chronic pain conditions and represented 42 distinct antidepressant vs. placebo comparisons. There were five reviews on fibromyalgia and two each for neuropathic pain and chronic tension-type headache. All other conditions were covered by a single review.

A total of 11 comparisons, consisting of nine conditions, found antidepressants to be effective, though with varying evidence of certainty. Moderate certainty of evidence was found for only four conditions treated with serotonin-norepinephrine reuptake inhibitors (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).

There was low-certainty evidence that SNRI treatment was effective for aromatase inhibitor therapy-induced pain in breast cancer, depression and comorbid chronic pain and knee osteoarthritis. In addition, there was low-certainty evidence that selective serotonin reuptake inhibitor treatment was effective for depression and comorbid chronic pain, and that tricyclic antidepressants were effective for irritable bowel syndrome, neuropathic pain and chronic-tension headache.

For the remaining comparisons, five were not effective and 26 were ruled as inconclusive.

Meanwhile, safety and tolerability were found to be indefinite for most treatments.

The researchers wrote that caution should be taken when interpreting the results “because 45% of the trials forming the body of evidence for this review had ties to industry.”

“This is particularly relevant for the evidence on the efficacy of SNRIs, where 68% of trials were identified as having industry ties,” they wrote.

Future reviews, they added, should use sensitivity analyses when considering industry funding.

Additionally, Ferreira and colleagues wrote that for comparisons which did find efficacy, the clinical relevancy was still unknown.

For back pain, postoperative pain and neuropathic pain, “the reduction of pain compared with placebo was smaller than 10 points on a 0-100 scale,” they wrote. “For fibromyalgia, where outcomes were measured as the proportion of participants with at least a 50% reduction in pain, 31% of people receiving an SNRI improved, which translates to an absolute risk reduction of 9%.”

Due to the uncertainty of the findings, Ferreira and colleagues encouraged clinicians to hold “holistic assessments” 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.”