Antidepressants offer slight benefit for back pain, osteoarthritis

Serotonin-noradrenaline reuptake inhibitors (SNRIs) provide a small influence on pain and disability scores and appear to have no clinically significant benefit for back pain, as shown by moderate certainty evidence from a systematic review and meta-analysis. However, such effect cannot be ignored for osteoarthritis (OA). Moreover, tricyclic antidepressants (TCAs) and SNRIs may benefit patients with sciatica, but the certainty of evidence is low to very low.

“Although the observed effect of SNRIs in reducing back pain and related disability was statistically significant, the magnitude of such effects was too small to be considered clinically important,” the researchers said.

The databases of Medline, Embase, Cochrane Central Register of Controlled Trials, Cinahl, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to 15 November 2020. Randomized controlled trials comparing the efficacy or safety, or both, of any antidepressant drug with placebo in participants with low back or neck pain, sciatica, or hip or knee OA were included.

Two independent reviewers extracted data. Weighted mean differences and 95 percent confidence intervals (CIs) were calculated using a random effects model. Finally, the researchers assessed risk of bias using the Cochrane Collaboration’s tool and certainty of evidence with the grading of recommendations assessment, development, and evaluation (GRADE) framework.

Thirty-three trials, comprising 5,318 participants, met the eligibility criteria. At 3–13 weeks, SNRIs reduced back pain (mean difference [MD], –5.30, 95 percent CI, –7.31 to –3.30) based on moderate certainty evidence and reduced OA pain (MD, –9.72, 95 percent CI, –12.75 to –6.69) on low certainty evidence. [BMJ 2021;372:m4825]

Very low certainty evidence demonstrated the effectiveness of SNRIs in reducing sciatica at 2 weeks or less (MD, –18.60, 95 percent CI, –31.87 to –5.33) but not at 3–13 weeks (MD, –17.50, 95 percent CI, –42.90 to 7.89). TCAs, on the other hand, did not reduce sciatica at 2 weeks or less (MD, –7.55, 95 percent CI, –18.25 to 3.15) but did at 3–13 weeks (MD, –15.95, 95 percent CI, –31.52 to –0.39) and 3–12 months (MD, –27.0, 95 percent CI, –36.11 to –17.89) based on low to very low certainty evidence.

Furthermore, moderate certainty evidence showed that SNRIs effectively reduced disability from back pain at 3–13 weeks (MD, –3.55, 95 percent CI, –5.22 to –1.88) and disability due to OA at 2 weeks or less (MD, –5.10, 95 percent CI, –7.31 to –2.89), with low certainty evidence at 3–13 weeks (MD, –6.07, 95 percent CI, –8.13 to –4.02). TCAs and other antidepressants, however, failed to reduce pain or disability from back pain.

Of note, recommendations provided by the UK and US guidelines on the use of SNRIs for back pain are inconsistent. [Ann Intern Med 2017;166:514-530; https://pubmed.ncbi.nlm.nih.gov/27929617/]

“Our review shows that although these medicines are effective, the effect is small and unlikely to be considered clinically important by most patients. Our review also showed that about two-thirds of patients using SNRIs experience adverse events,” the researchers said.

“We would encourage clinicians to share all this information about SNRIs with patients to allow them to make an informed decision,” they added.