A Systematic Review of Duloxetine for Osteoarthritic Pain: What is the Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed?

Abstract

Duloxetine appears efficacious and tolerable for the treatment of chronic pain associated with OA. The NNT and NNH can be used to quantify efficacy and tolerability outcomes and help place duloxetine into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and patient the trade-offs between obtaining potential benefits versus harms. Head-to-head comparisons of duloxetine with other interventions for OA, as well as controlled trials of duloxetine in combination with other therapies, would be desirable.

Antidepressants and the relief of osteoarthritic pain - Findings from a study examining adjunctive duloxetine

“…The published report provides the percentage of patients with each adverse event: nausea (duloxetine, 15.5% vs. placebo, 4.6%; NNH 10), dry mouth (9.5% vs. 2.7%; NNH 15), constipation (8.7% vs. 3.1%; NNH 18), dizziness (6.4% vs. 2.7%; NNH 27), fatigue (6.8% vs. 1.5%; NNH 19) and decreased appetite (5.7% vs. 0.4%; NNH 19). These are consistent with the monotherapy trials; however, nausea, dry mouth and decreased appetite were more frequently encountered in the combination trial (4). Bleeding‐related adverse events occurred in four patients in the duloxetine group (epistaxis, haematochezia, decreased haematocrit, easy bruising) vs. one patient in the placebo group (haematoma), with no bleeding adverse event classified as serious.…”

“…We recently published elsewhere a systematic review of duloxetine monotherapy for osteoarthritic pain (4). We quantified the clinical relevance of the statistically significant results from the 13‐week duloxetine studies using number needed to treat (NNT) and found that the NNT for duloxetine vs. placebo for treatment relief using a composite measure was six (95% CI 4–10), which overlaps with the 95% CI observed with the NNT for response for other treatments, such as etodolac after 4 weeks (NNT 5, 95% CI 3–25) and tenoxicam after 8 weeks (NNT 4, 94% CI 3–8), as calculated in systematic reviews for OA (5).…”

“…Although the duloxetine monotherapy trials included path analyses to demonstrate duloxetine’s direct analgesic effect rather than it being dependent on improvement in depression or anxiety symptoms (4), there is no mention of this being done for the data collected in the adjunctive duloxetine study (6).…”

OARSI guidelines for the non-surgical management of knee osteoarthritis

“…A 2012 SR and a 2011 RCT comparing duloxetine with oral placebo found duloxetine efficacious and tolerable for chronic pain associated with OA 50,51 . Pooled analysis found that 16.3% of the patients who received duloxetine withdrew due to adverse events compared with 5.6% of those receiving placebo 50 . The most commonly reported adverse events included nausea, dry mouth, somnolence, fatigue, constipation, decreased appetite, and hyperhidrosis.…”

Obesity is Associated with an Increased Prevalence of Glenohumeral Osteoarthritis and Arthroplasty

“…As Evidence exists for treating OA pain as, at least in part, neuropathically mediated, with serotonin-norepinephrine reuptake inhibitors, primarily [42][43][44][45] , but also venlafaxine 46 , both showing effect. Indeed, the strength of evidence for duloxetine's pain-reducing effect was sufficient enough that it is now FDA-approved for this indication 47 . Similarly, two other neuromodulators in gabapentin 48 and lacosamide 49,50 have been successfully used to treat the pain of OA.…”