Objective: To describe the efficacy, safety, and tolerability of duloxetine for the treatment of osteoarthritic pain.
Data sources: Systematic review of all published double-blind randomized controlled trials of duloxetine for osteoarthritic pain, supplemented by information in clinical trial registries, product labeling, and regulatory documents.
Study selection: All available reports of studies were identified.
Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) for pain relief and other efficacy outcomes and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.
Data synthesis: US Food and Drug Administration approval for duloxetine for chronic pain associated with osteoarthritis (OA) was based on 2 randomized, double-blind, placebo-controlled clinical trials of 13 weeks' duration testing duloxetine 60 to 120 mg/d versus placebo. When study results were pooled, the proportion of patients experiencing clinically meaningful outcomes at study endpoint, such as a ≥ 30% or ≥ 50% reduction in pain scores, improvement in physical functioning, or subjective improvement, ranged from 42% to 67% for duloxetine, compared with 26% to 50% for placebo, depending on the specific measure; the NNT for these measures for duloxetine versus placebo was 7. The most commonly observed adverse reactions in duloxetine-treated patients were nausea (8.4% vs 2.0% for duloxetine and placebo, respectively), fatigue (6.7% vs 0.8%, respectively), and constipation (6.3% vs 0.8%, respectively), yielding NNH values of 16, 17, and 19, respectively. The LHH was consistently > 1.
Conclusions: 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.