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?

Objective: To describe the efficacy, safety, and tolerability of duloxetine for the treatment ofosteoarthritic pain. Data sources: Systematic review of all published double-blind randomizedcontrolled trials of duloxetine for osteoarthritic pain, supplemented by information in clinicaltrial registries, product labeling, and regulatory documents. Study selection: All availablereports of studies were identified. Data extraction: Descriptions of the principal results andcalculation of number needed to treat (NNT) for pain relief and other efficacy outcomes andnumber needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted.Likelihood to be helped or harmed (LHH) was subsequently calculated. Data synthesis: USFood and Drug Administration approval for duloxetine for chronic pain associated with osteoarthritis(OA) was based on 2 randomized, double-blind, placebo-controlled clinical trials of13 weeks' duration testing duloxetine 60 to 120 mg/d versus placebo. When study results werepooled, 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, orsubjective 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 duloxetineversus placebo was 7. The most commonly observed adverse reactions in duloxetine-treatedpatients 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 of16, 17, and 19, respectively. The LHH was consistently > 1. Conclusions: Duloxetine appearsefficacious and tolerable for the treatment of chronic pain associated with OA. The NNT andNNH can be used to quantify efficacy and tolerability outcomes and help place duloxetine intoclinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and patientthe trade-offs between obtaining potential benefits versus harms. Head-to-head comparisons ofduloxetine with other interventions for OA, as well as controlled trials of duloxetine in combinationwith other therapies, would be desirable. © Postgraduate Medicine.