Antidepressant Gets FDA Nod to Treat Fibromyalgia

Duloxetine (Cymbalta), a drug manufactured by Eli Lilly and Co., has been approved by the Food and Drug Administration (FDA) for the treatment of fibromyalgia, a syndrome of chronic, diffuse muscle and joint pain that leads to impaired functioning.

The drug is only the second approved for this indication; the first is pregabalin (Lyrica) manufactured by Pfizer. Duloxetine has previously been approved to treat major depression, anxiety disorder, and pain due to diabetic peripheral neuropathy in adults. The dosage approved for treating fibromyalgia is 60 mg once daily.

The approval was based on two phase 3, randomized, double-blind, placebo-controlled clinical trials of duloxetine involving 874 patients with fibromyalgia, according to the updated product label. About a quarter of these study patients had comorbid major depressive disorder.

Duloxetine 60 mg, taken once or twice daily, reduced the severity of pain—as assessed by the Brief Pain Inventory scale—to a larger extent than placebo at the end of three months in one trial and six months in the other trial. Patients' assessment of functioning on the Fibromyalgia Impact Questionnaire was also improved with the active treatment. The 120 mg daily dosage was not significantly more efficacious than the 60 mg daily dosage in these trials.

In all four clinical trials in fibromyalgia that the company has conducted, the most common adverse events that occurred twice as often in duloxetine-treated patients as in placebo-treated ones included nausea, dry mouth, constipation, decreased appetite, sleepiness, increased sweating, and agitation.

The mechanism of action of duloxetine, a serotonin and norepinephrine reuptake inhibitor, on fibromyalgia is unknown, in part because scientists so far know very little about the causes and physiological process of this syndrome. According to the criteria established by the American College of Rheumatology in 1990, the diagnosis of fibromyalgia is based on the following symptoms: a history of widespread pain for at least three months that involves pain on the right and left sides of the body, above and below the waist, and in the axial skeleton; and pain in at least 11 of 18 tender point sites on digital palpation.

Women make up 80 percent to 90 percent of those diagnosed with fibromyalgia, which can significantly reduce patients' functioning and quality of life. Comorbid depression and anxiety are frequently seen in these patients, and some researchers have suspected shared genetic and neurological factors between depression and fibromyalgia (Psychiatric News, September 17, 2004).

Eli Lilly is also studying the effect of duloxetine in osteoarthritis pain. Results from a 13-week study of 231 patients, presented at the annual congress of the European League Against Rheumatism in June, suggested that duloxetine treatment led to significantly greater pain reduction than did placebo in patients with arthritis of the knee.

The updated prescribing information for duloxetine is posted at<pi.lilly.com/us/cymbalta-pi.pdf>.▪