Most antidepressants ineffective for common pain conditions, review finds

The systematic review found no high-certainty evidence supporting the effectiveness of antidepressants for pain, and the only moderate-certainty evidence was for serotonin-norepinephrine reuptake inhibitors to treat back pain, postoperative pain, neuropathic pain, and fibromyalgia.

While some antidepressant drugs were found to be effective for some pain conditions, most are either ineffective or the evidence is inconclusive, a systematic review concluded.

Researchers conducted a systematic review of any study comparing any antidepressant with placebo for any pain condition in adults. They found 26 evidence reviews published between 2012 and 2022, involving 156 separate trials and more than 25,000 participants. The studies reported on the effectiveness of eight classes of antidepressants used for 22 pain conditions (42 comparisons of antidepressants vs. placebo). Almost half of the trials (45%) had industry ties. The review authors estimated relative risks of pain or average differences in pain between groups on a scale from 0 to 100, taking dose, treatment duration, and number of trials and participants into account. They also assessed safety and tolerability (withdrawals due to adverse events), certainty of evidence, and risk of bias. Results were published Feb. 1 by The BMJ.

None of the reviews provided high-certainty evidence on the effectiveness of antidepressants for pain for any condition, the review found. Antidepressants showed efficacy in 11 comparisons (nine conditions), four with moderate-certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for 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 (risk ratio, 1.4; 95% CI, 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious in five cases or the evidence was inconclusive in 26 cases.

The authors cautioned that safety of antidepressants for several conditions is still uncertain because most safety and tolerability data were imprecise. They wrote, “Some antidepressants were efficacious for some pain conditions; however, efficacy appears to depend on the condition and class of antidepressant. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain.”

An accompanying editorial observed that antidepressant treatment will be disappointing for most adults living with chronic pain. Clinicians likely continue to prescribe medicines for which the evidence is poor because they see that some people respond to them, the editorialists noted, adding that exercise and support with mobility and social isolation can also help people to live well with pain.

“For people with pain, compassionate and consistent relationships with clinicians remain the foundations of successful care,” the editorial stated. “Research shows that what people want most is a strong, empathic relationship with their care provider. They want time to discuss what matters to them and they want easy access to support.”