Is pain effectively treated with antidepressants?

While some antidepressant medications were effective for some pain conditions, many were either ineffective or the evidence was inconclusive, a review found.

Evidence for the effectiveness of antidepressants for pain was found 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, the evidence was of moderate certainty. They included serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain, postoperative pain, fibromyalgia, and neuropathic pain, they wrote. BMJ.

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

Recent data suggest that chronic pain is the most common condition leading to new antidepressant use among older adults in the US, UK, Canada and Taiwan – even more so than depression, the researchers noted.

“Prescribing a list of antidepressants without carefully considering the evidence for each of those antidepressants for different pain conditions can mislead physicians and patients into thinking that all antidepressants have equal efficacy for pain conditions,” Ferreira said in a statement. “We have shown that this is not the case.”

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

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

Cathy Stannard, MBChB, and Colin Wilkinson, a lay member, from the Gloucestershire Integrated Care Board, National Health Service (NHS) Gloucester, England, said the findings suggest that for most adults living with chronic pain, antidepressant treatment is frustrating. of the Pain Consortium at the University of Bath, England.

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

“For people in pain, a compassionate and ongoing relationship with physicians is the foundation of successful care,” they point out.

“Research shows that what people want is a strong, empathetic relationship with their care provider,” the editors continued. “They want time to discuss what’s important 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 spanning 156 trials and 25,000 participants between 2012 and 2022.

Those reviews reported on eight classes of antidepressants covering 22 pain conditions, including 42 antidepressant versus placebo comparisons. Industry ties were present in 45% of 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 the continuous results to a scale of 0 (no pain) to 100 (worst pain) and presented the findings as mean differences. Dichotomous outcomes were presented as risk ratios (RR).

No review has provided highly definitive evidence about the effectiveness of antidepressants for pain for any condition.

Four reviews reported moderate certainty 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) showed evidence. -6.8, 95% CI -8.7 to -4.8), and fibromyalgia (RR 1.4, 95% CI 1.3-1.6).

Less definitive evidence suggested that SNRIs were effective for pain associated with breast cancer treatment, knee osteoarthritis, and comorbid pain with depression. Less certain evidence also suggested that selective serotonin reuptake inhibitors (SSRIs) were effective for depression and comorbid pain, and 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 significance of the observed effects for each condition because commonly used thresholds, such as a 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,” noted Ferreira and colleagues.

“Given the challenges of making judgment calls about the clinical relevance of treatment effects, we encourage clinicians to first evaluate the overall evidence, including an assessment of effect size, the certainty of available evidence, and trade-offs between the benefits and harms of each antidepressant, and then have these discussions with patients. To include,” they added.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. to follow


Ferreira and two co-authors disclose support from National Health and Medical Research Council (NHMRC) fellowships. Co-authors disclose affiliations with industry and non-profit groups.

Stannard disclosed that he serves as a member of the NICE guidelines for pain and pain medication guidelines in the UK Wilkinson as a top advisor for clinical leadership and the National Institute for Health and Care Excellence (NICE).

primary source


Source Reference: Ferreira GE, et al “Efficacy, safety, and tolerability of antidepressants for pain in adults: an overview of systematic reviews” BMJ 2023; DOI: 10.1136/bmj-2022-072415.

secondary source


Source Reference: Stannard C and Wilkinson C “Rethinking the use of drugs for chronic pain” BMJ 2023; DOI: 10.1136/bmj.p170.

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