Diabetic peripheral neuropathy
Duloxetine was approved for the pain associated with diabetic peripheral neuropathy (DPN), damage to nerves that can develop in people who have diabetes, based on the positive results of two clinical trials. The average daily pain was measured using an 11-point scale, and duloxetine treatment resulted in an additional 1–1.7 points decrease of pain as compared with placebo.At least 50% pain relief was achieved in 40–45% of the duloxetine patients vs. 20–22% of placebo patients. The pain almost completely disappeared, decreasing by more than 90%, in 9–14% of duloxetine patients vs. 2–4% of placebo patients. Most of the response was achieved in the first two weeks on the medication. Duloxetine slightly increased the fasting serum glucose; however this effect was deemed to be of "minimal clinical significance".
Duloxetine was not effective for the numbness or tingling, nor for the other complications of diabetes. It reduced the pain without treating the underlying nerve damage. Only tight glycemic control was unequivocally demonstrated to slow the progression of neuropathy. Benfotiamine, alpha-lipoic acid, and ranirestat have also shown some promise.
The comparative efficacy of duloxetine and established pain-relief medications for DPN is unclear. An independent systematic review in BMJ noted that tricyclic antidepressants (imipramine andamitriptyline), traditional anticonvulsants and opioids have better efficacy than duloxetine. Duloxetine, tricyclic antidepressants and anticonvulsants have similar tolerability while the opioids caused more side effects. A review in Drug and Therapeutic Bulletin saw no place for duloxetine in the treatment of DPN, based on its high cost and insufficient evidence of the comparative efficacy with tricyclic antidepressants. Another independent review in Prescrire International, considered the moderate pain relief achieved with duloxetine to be clinically insignificant and the results of the clinical trials—unconvincing. The reviewer saw no reason to prescribe duloxetine in practice. The comparative data collected by reviewers in BMC Neurology indicated that amitriptyline, other tricyclic antidepressants and venlafaxine may be more effective. However, the authors noted that the evidence in favor of duloxetine is much more solid.
Generalized anxiety disorder
Duloxetine is as effective as venlafaxine in the treatment of generalized anxiety disorder, excessive worry and tension that disrupts daily life and lasts for 6 months or longer, with demonstrated improvements in function and quality of life for sufferers. Long-term use of duloxetine prevents relapse of generalized anxiety disorder. Although this view was repeated in a recent independent review, the major guidelines such as Maudsley Prescribing Guidelines, Mayo Clinic Health Information and Canadian Psychiatric Association Guidelines do not mention duloxetine among the recommended treatment options.
On October 19, 2006, Eli Lilly issued a press release saying they had done trials which found that Cymbalta (duloxetine), at 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia (FM), a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep, with and without major depression, according to 12-week data presented at the annual meeting of the American College of Rheumatology. Eli Lilly has been promoting Cymbalta for FM since 2004.
Duloxetine is superior to many other medications for the treatment of fibromyalgia due to its freedom from muscarinic, histaminergic and adrenergic adverse reactions. Its effectiveness in pain relief is believed to be due to its modulation of the nociception system. A meta-analysis of clinical trials has confirmed its pain relief, fatigue reducing properties as well as its effectiveness in improving physical and mental performance.
In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study. Researchers also tested the participants for depression.
Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo. For men, who made up only 11% of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study.
However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the 12-week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time.
The Food and Drug Administration regulators approved the drug for the treatment of fibromyalgia in June 2008.