Most antidepressants are ineffective for pain relief – or evidence to support their use is inconclusive, according to new analysis published last night.
Antidepressant use doubled in OECD countries from 2000 to 2015 and their off-label use to treat common pain conditions such as fibromyalgia, persistent headaches and osteoarthritis is thought to be part of this increase.
A team of researchers at the University of Sydney, Australia, carried out an overview of the effectiveness, safety, and tolerability of antidepressants for pain according to condition.
The team, led by Giovanni Ferreira, searched databases for systematic reviews that compared any antidepressant with placebo for any pain condition in adults. They found 26 eligible evidence reviews published between 2012 and 2022 involving 156 separate trials and more than 25,000 participants.
These reviews reported on the effectiveness of eight classes of antidepressant covering 22 pain conditions, totalling 42 distinct antidepressant compared to placebo comparisons. Almost half (45%) of the trials had ties to industry.
The researchers estimated relative risks of pain or average differences in pain between groups on a 0 to 100 point scale, taking account of dose, treatment duration, and number of trials and participants.
They also assessed safety and tolerability, certainty of evidence, and risk of bias. Findings were classified from each comparison as effective, not effective, or inconclusive.
No review provided high certainty evidence on the effectiveness of antidepressants for pain for any condition, while nine provided evidence that some antidepressants were effective compared with placebo for nine conditions in 11 distinct comparisons.
These reviews included moderate certainty evidence to suggest serotonin-norepinephrine reuptake inhibitors (SNRIs) were effective for back pain, postoperative pain, fibromyalgia, and neuropathic pain.
Evidence suggesting SNRIs were effective for pain linked to breast cancer treatment, depression, knee osteoarthritis and pain related to other underlying conditions was “low certainty”, they report.
There was also low certainty evidence that selective serotonin reuptake inhibitors (SSRIs) were effective for people with depression and pain related to other conditions; and that tricyclic antidepressants (TCAs) were effective for irritable bowel syndrome, neuropathic pain, and chronic tension-type headache.
For the other 31 comparisons, antidepressants were either not effective or the evidence was inconclusive.
The authors say while their research was well designed, most comparisons had a limited number of trials, and results may not apply to antidepressants prescribed for symptoms linked to pain conditions, such as fatigue or sleep disturbance.
They also urge caution when interpreting their findings because 45% of the trials had ties to industry.
“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.,” they conclude.
Ferreira G, Abdel-Shaheed C, Underwood M et al. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews *BMJ* 1 February 2023
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