DULOXETINE FOR PERIPHERAL NEUROPATHY 

Patients treated with neurotoxic forms of chemotherapy are often left with a painful peripheral neuropathy that persists long after treatment of their cancer has concluded. A variety of drugs have been used to treat this common condition with minimal success. Duloxetine is a serotonin and norepinephrine dual reuptake inhibitor that has recently been demonstrated to be effective in patients with painful diabetic neuropathy. Lavoie Smith and colleagues (2013) examined the effect of duloxetine on patients with chemotherapy-induced painful peripheral neuropathy.

The authors designed a randomized, double-blind, placebo-controlled crossover trial. Patients who were recruited carried a diagnosis of chemotherapy-induced peripheral neuropathy and were at least 25 years of age. All eligible patients had at least grade 1 pain based on a standard scale and reported 4 of 10 average pain for 3 or more months after finishing chemotherapy with paclitaxel, oxaliplatin, docetaxel, or cisplatin. Patients were randomized to either 30 mg of duloxetine for 1 week followed by 60 mg of duloxetine for 4 weeks or placebo for 5 weeks. After a 2-week washout period, the groups crossed over for an additional 5-week period. Patient-reported weekly pain was assessed with the Brief Pain Inventory (Short Form).

A total of 231 patients were enrolled in the study, and 220 received treatment. Patient characteristics were similar in the two groups except for baseline mean pain scores, which were higher in the duloxetine group (mean score, 6.1 vs 5.6; p = .02). The dropout rate was significantly higher in the duloxetine group (11% vs 1%; p<.001), although reported adverse events were not significantly different between the groups.

The primary outcome examined, pain scores at the end of the first part of the trial, showed that there was a significantly larger decrease in average pain in the duloxetine first group compared with placebo first group (mean decrease in average pain score, 1.06 vs 0.34; p = .003; effect size, 0.513). The observed mean difference in average pain score between the groups was 0.73 (95% confidence interval, 0.26–1.20). Of the patients treated with duloxetine first, 59% reported any decrease in pain compared with 38% of patients treated with placebo first.

Secondary outcomes examined revealed improvements in daily function and pain-related quality of life with duloxetine treatment. There were also modest benefits in nonpainful symptoms, including numbness and tingling in the feet, as well as a reduction in the use of ancillary analgesics.

The benefits of duloxetine found in this study are similar to those found in trials of painful diabetic neuropathy. It is not clear if this effect would be seen with other medications from the same class. For now, clinicians caring for patients with painful chemotherapy-induced neuropathy should consider using duloxetine to reduce pain and improve quality of life.