Duloxetine (sold under the brand names Cymbalta, Ariclaim, Xeristar, Yentreve, Duzela, Dulane) is a serotonin-norepinephrine reuptake inhibitor (SNRI) manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and generalized anxiety disorder (GAD). Duloxetine has approval for use in osteoarthiritis and musculoskeletal pain. Duloxetine failed the US approval for stress urinary incontinence amidst concerns over liver toxicity and suicidal events; however, it was approved for this indication in Europe, where it is recommended as an add-on medication in instead of surgery. It can also relieve the symptoms of painful peripheral neuropathy, particularly diabetic neuropathy, and it is used to control the symptoms of fibromyalgia.
The main uses of duloxetine are in major depressive disorder, general anxiety disorder, stress urinary incontinence, painful peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain associated with osteoarthritis and chronic . It is being studied for various other indications.
Major depressive disorder
Duloxetine has demonstrated efficacy for the treatment of major depressive disorder. In a small, clinical study supported by the manufacturer, duloxetine was also shown to be effective in elderly patients with recurrent major where it improved cognition, depression, and some pain measures.
Stress urinary incontinence
Duloxetine was first reported to improve outcomes in stress urinary incontinence (SUI) in 1998. Systematic reviews with meta-analysis, conducted in 2005 by Cochrane Collaboration and in 2008 by University of Minnesota, concluded that duloxetine failed to cure SUI better than placebo. According to the Cochrane review, some studies showed that episodes of incontinence were reduced by about 50%. This was associated with an improvement in quality of life measurements.
According to the University of Minnesota review, duloxetine performed worse than oxybutynin (Ditropan) or tolterodine (Detrol) that cured 18% of the cases, or than pelvic floor muscle training + bladder training, which cured 13% of the cases. In terms of "improvement", that is incomplete cure, duloxetine showed improvement in 11% of patients while pelvic floor muscle training + bladder training showed improvement in 36% of the cases. Significant side effects were common with duloxetine; they were reported as acceptable and about a fifth had to discontinue the medication because of poor tolerance.
In addition, the full report prepared by Minnesota Evidence-based Practice Center for the U.S. government, on which the University of Minnesota review is based, notes that weight reduction would result in improved SUI in 990 adults per 1,000 treated. In the light of the cited data, the report does not mention duloxetine in its policy recommendations. The only recommended interventions are early behavioral changes in weight, physical activity, and pelvic floor muscle training.
The only clinical trial, which directly compared duloxetine with the gold standard of the SUI treatment pelvic floor muscle training (PFMT) was conducted by Eli Lilly and gave mixed results. The incontinence episode frequency in duloxetine group decreased by 57% vs. 35% in the PFMT group. However, the differences in the pad use and quality of life were not statistically significant. To the contrary, 65% patients doing PFMT reported feeling better vs 54% of the patients on duloxetine. 31% of the patients on duloxetine discontinued the trial due to the side effects during the first 12 weeks. In the continuation of this trial more than 91% of the patients on duloxetine experienced side effects.
Summing up the existing evidence, a review in Prescrire International recommends pelvic floor exercises, which are "risk-free and effective in two-thirds to three-quarters of cases", as the first line treatment of SUI. Duloxetine use reduced the frequency of stress incontinence by one episode a day as compared with placebo. "The tangible effect of duloxetine on the quality of life is doubtful, with a maximum gain of five points on a 100-point scale." The review notes that, at best, duloxetine efficacy is "modest and transient, while its adverse effects are numerous and potentially severe."