DULOXETINE FOR NEUROPATHETIC PAIN

Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy: A Randomized Clinical Trial

Smith EM, Pang H, Cirrincione C, et al

JAMA. 2013;309:1359-1367

Study Summary

There are no evidence-based effective treatments for painful chemotherapy-induced neuropathy. In this randomized, double-blind, placebo-controlled crossover trial, 231 patients were randomly assigned to receive duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to National Cancer Institute Criteria for Adverse Events and at least average chemotherapy-induced pain -- quantified as at least a 4 on a scale of 0 to 10 -- after paclitaxel, other taxane, or oxaliplatin treatment.
Individuals who received duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). Fifty-nine percent of those who initially received duloxetine vs 38% of those who initially received placebo reported decreased pain of any amount. An exploratory analysis suggested that patients who received platinums (oxaliplatin) experienced more benefit from duloxetine than those who received taxanes, but this finding was not statistically significant (P = .13). The dropout rate related to adverse events in the duloxetine-first group was 11% vs 1% in the placebo-first group (P <.001).

Viewpoint

Approximately one third of patients who receive neurotoxic agents such as taxanes, platinums, vinca alkaloids, or bortezomib can develop painful neuropathy that significantly interferes with quality of life and function. Agents such as duloxetine have been shown to be helpful in other painful neuropathy syndromes such as diabetic neuropathy. This is the first large phase 3 study to evaluate the benefit of duloxetine in chemotherapy-induced painful neuropathy.
The magnitude of the clinical effect is comparable to that achieved by duloxetine in other situations, such as diabetic neuropathy, and therefore appears clinically meaningful. However, the high dropout rate resulting from adverse effects is concerning. In addition, clinicians should be aware of potential drug-drug interactions, including cytochrome P450 inhibition, inhibition of metabolic conversion of tamoxifen, and increased bleeding risk with warfarin.