Antidepressants: Duloxetine for patients with diabetic neuropathic pain: a six-month open label safety study

Abstract

Duloxetine is a balanced and potent reuptake inhibitor of both serotonin (5-HT) and norepinephrine (NE). Since 5-HT and NE inhibit pain via descending spinal cord pathways, duloxetine's dual reuptake inhibition activity may make it an effective agent for the treatment of diabetic neuropathic pain. In a 28-week, multicenter, open-label study, 449 patients diagnosed with diabetic neuropathic pain (DN) were randomized 3:1 to either duloxetine 60 mg BID or duloxetine 120 mg QD treatment groups. The primary study objective was to assess duloxetine's tolerability and safety in DN patients. Standard clinical tests, labs and ECGs were performed for all patients. Secondary efficacy measures included the Brief Pain Inventory (BPI) and Clinical Global Impression of Severity (CGI-S) scales. Protocol completion rates were 63.8% and 62.6% for the duloxetine 60 mg BID (n=213) and duloxetine 120 mg QD (n=72) patient groups, respectively. Both treatment groups showed improvement from baseline to endpoint on all subscales of the BPI and the CGI-S (p < .005). Adverse events were the most frequent cause of discontinuation for both treatment groups. Statistically significant but clinically unremarkable changes occurred in some cardiovascular parameters from baseline to endpoint. In both duloxetine treatment groups, heart rate increased slightly (p < .05) and systolic blood pressure (BP) was unaffected while diastolic BP decreased slightly in duloxetine 120 mg QD patients (p < .05). A sustained (3 consecutive visits) BP elevation was reported for 18 (5.5%) and 6 (5.4%) of patients receiving duloxetine 60 mg BID and duloxetine 120 mg QD, respectively. For patients with diabetic neuropathic pain, duloxetine is tolerable as demonstrated by its high percentage of patients completing the study, can be safely administered,; and was efficacious in improving the painful symptoms associated with diabetic neuropathy