Objective: Duloxetine is a relatively balanced and potent reuptake inhibitor of both serotonin and norepinephrine. Because these neurotransmitters play a role in pain inhibition, duloxetine was considered a possible treatment for diabetic peripheral neuropathic pain (DPNP). This study assessed the 6-month safety and tolerability of duloxetine in patients with DPNP; evaluation of efficacy was a secondary objective.

Design: In this 28-week, open-label study, in the clinical setting, 449 patients with DPNP were randomized (3:1) to receive duloxetine 60 mg twice daily (BID) (N = 334) or duloxetine 120 mg once daily (QD) (N = 115). Comprehensive safety evaluations including laboratory analyses and electrocardiograms were performed for all patients. Efficacy measures included the Brief Pain Inventory (BPI) and Clinical Global Impression of Severity (CGI-S) scales.

Results: Protocol completion rates were 63.8% and 62.6% for the 60 mg BID and 120 mg QD groups, respectively (P = 0.823). Discontinuations were primarily due to adverse events, 20.1% for 60 mg BID and 27.0% for 120 mg QD (P = 0.149). Heart rate increased slightly in both treatment groups (P </= 0.02 in both groups). Systolic blood pressure was unaffected, while diastolic blood pressure decreased slightly in the 120 mg QD group (P = 0.04). Sustained elevation in blood pressure was reported for 18 (5.5%) patients in the 60 mg BID group and six (5.4%) in the 120 mg QD group. Duloxetine treatment was not associated with significant QTc prolongation. There was significant improvement at endpoint on all subscales of the BPI and CGI-S (P < 0.001 in both groups).

Conclusions: In this study, duloxetine 60 mg BID and 120 mg QD were safely administered and well tolerated in patients with DPNP for up to 28 weeks. There were few differences in safety or tolerability between the two dosages. At both doses, duloxetine provided clinically significant pain relief.