Superiority of duloxetine to placebo in improving diabetic neuropathic pain: Results of a randomized controlled trial in Japan

Aims/Introduction: Duloxetine has been suggested to exert analgesic effects by activating the descending inhibitory system through inhibition of serotonin (5‐HT) and noradrenaline (NA) reuptake. This randomized controlled trial investigated the efficacy and safety of duloxetine in Japanese patients with diabetic neuropathic pain (DNP). Materials and Methods: Duloxetine 40 or 60 mg/day or placebo was given orally once daily for 12 weeks. The primary efficacy measure was weekly mean 24‐h average pain severity score on the 11‐point Numerical Rating Scale. Results: At 12 weeks vs baseline, the 24‐h average pain score (adjusted mean ± SE) was significantly improved in the combined duloxetine (−2.47 ± 0.18) and duloxetine 40 mg (−2.41 ± 0.21) and 60 mg groups (−2.53 ± 0.21) as compared with the placebo group (−1.61 ± 0.18). Duloxetine also exerted significant improvements over the placebo in nearly all secondary outcome measures including 24‐h worst pain, night pain, Brief Pain Inventory (BPI) pain scores, Patient’s Global Impression of Improvement (PGI‐I) and health outcome measures, namely, various BPI interference scores. The incidence of adverse events (AE) was higher in the duloxetine groups than in the placebo group (duloxetine overall, 84.8%; duloxetine 40 mg, 84.7%; duloxetine 60 mg, 84.9%; placebo, 73.7%). Most AE were mild or moderate in severity, and resolved or relieved. There were no clinically significant safety concerns. Conclusions: Duloxetine 40 or 60 mg/day showed superiority over the placebo at reducing pain scores in patients with DNP. Duloxetine is safe, efficacious and clinically useful in the management of DNP. This trial was registered with ClinicalTrials.gov (no. NCT‐00552175). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00073.x, 2010)