Duloxetine for patients with diabetic peripheral neuropathic pain: a 6-month open-label safety study.
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.


METHODS
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.
Raskin
Joel
J
Lilly Research Laboratories, Eli Lilly Canada, Toronto, Canada. raskin_joel@lilly.com
Wang
Fujun
F
Pritchett
Yili Lu
YL
Goldstein
David J
DJ
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068736:Duloxetine Hydrochloride; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013610:Tachycardia / Q000139:chemically induced; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes