by Jeanne Hambleton © 2008
NFA Leader Against Pain-Advocate
It is great news from the USA with a second fibromyalgia drug now approved by the FDA (Food & Drugs Administration).
The news released by PRNewswire reveals the new drug called Cymbalta (R) (duloxetine HCl), manufactured by Eli Lilly & Company (NYSE: LLY), a leading worldwide pharmaceutical company, has been approved by the FDA as the first serotonin-norepinephrine reuptake inhibitor with proven efficacy for reducing pain in patients with fibromyalgia.
Patients suffering with osteoarthritis, who have taken the new drug, have already reported a reduction in the pain severity in their knees.
Madelaine Wohlreich, MD, and medical advisor and research physician at Lilly said, “The approval of Cymbalta is important because it provides physicians and patients with a new treatment option shown to help reduce pain and improve functioning in this difficult-to-treat disorder.”
While the cause of fibromyalgia remains unknown, scientists believe it may be related to some combination of changes in brain and spinal cord chemistry (i); or genetics (ii); and possible stress (iii). Many researchers claim fibromyalgia is a disorder of increased sensitivity to pain.
How Cymbalta works for people is not fully known, but medical experts believe it increases the activity of two naturally occurring substances called serotonin and norepinephrine. These substances help communication in various areas of the brain and spinal cord that affect emotion. Research also suggests that these substances are part of the body’s natural pain-suppressing system.
Lynne Matallana, president of the National Fibromyalgia Association who suffers with fibromyalgia, is reported to have said, “The FDA approval of Cymbalta for the management of fibromyalgia is another important step in the efforts to ensure that people with fibromyalgia will have the availability of effective medications to help reduce the chronic, widespread pain of this life-altering disorder.”
In the USA it is estimated that approximately 5 million people (2% of the US population) suffer with fibromyalgia. The victims are mainly women (iv), (v). There is no known cure for this condition, which causes widespread pain, chronic fatigue, insomnia, cognitive disorders, and many other problems.
Daniel Clauw, MD, professor of medicine in the University of Michigan’s Division of Rheumatology and director of the Chronic Pain and Fatigue Research Centre at the University of Michigan said, “In fibromyalgia, there is no one-size-fits-all approach to managing the disorder.”
Cymbalta has received four approvals from the FDA for different complaints. These include fibromyalgia, the management of diabetic peripheral neuropathic pain (DPNP); the treatment of major depressive disorder; and generalised anxiety disorder, for adults aged 18 years and older.
Lilly established the efficacy of Cymbalta in two pivotal three-month clinical trials involving 874 patients with fibromyalgia. In both studies, Cymbalta reduced pain at study end point compared with placebo as measured by the Brief Pain Inventory (BPI) 24-hour average pain scale. (vi),(vii). The BPI is a scale that measures the severity of pain.
Significant improvement in pain for Cymbalta vs. placebo was observed in the first week of each study. Fifty-one percent and 55 percent of patients on Cymbalta had a 30 percent improvement on the BPI at end point (clinically meaningful relief is considered at least 30 percent pain reduction (viii)).
In addition, 65 percent and 66 percent of patients taking Cymbalta, 60mg daily, reported feeling better at end point as measured by the Patient Global Impression of Improvement (PGI-I). The PGI-I is a patient-rated scale that evaluates how much improvement has occurred since beginning treatment.
Cymbalta 60 mg was superior to placebo on the Fibromyalgia Impact Questionnaire (FIQ) Total Score. The FIQ is a scale that is used to assess and evaluate the impact of fibromyalgia on aspects of health and functioning believed to be most affected by the disorder.
In four pooled studies, the most commonly observed adverse events in Cymbalta-treated patients with fibromyalgia (greater than or equal to 5 percent and at least twice placebo) were nausea (29 percent), dry mouth (18 percent), constipation (15 percent), decreased appetite (11 percent), sleepiness (11 percent), increased sweating (7 percent) and agitation (6 percent). In the placebo-controlled clinical trials, the overall discontinuation rates due to adverse events for Cymbalta vs. placebo were 20 percent and 12 percent, respectively. (ix)
Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate core mood symptoms and help regulate the perception of pain. Based on preclinical studies, Cymbalta is a balanced and potent reuptake inhibitor of serotonin and norepinephrine that is believed to potentate the activity of these chemicals in the central nervous system (brain and spinal cord). Scientists believe its effects on depression and anxiety symptoms, as well as its effect on pain perception, may be due to increasing the activity of serotonin and norepinephrine in the central nervous system.
In the important safety information, the company warns that anti depression medicines can increase suicidal thoughts. Patients are urged to contact their doctor in the event of any worsening depression symptoms or unusual changes.
Doctors and patients are warned that Cymbalta ‘is not for everyone’. Patients should talk to their doctors about other medical conditions to avoid complications. Patients taking Cymbalta may suffer with dizziness or feel faint when standing. The most common side effects of Cymbalta include nausea, dry mouth, sleepiness, and constipation. This is not a complete list of side effects. For full Patient Information, visit http://www.cymbalta.com. It is recommended that patients should consult their doctor before taking Cymbalta.
A six months trial under the heading ‘Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial’ was carried out at the University of Texas Health Science Center, San Antonio, TX, USA.
An abstract published by PubMed (NCBI) from the trial carried out by Russell IJ, Mease PJ, Smith TR, Kajdasz DK, Wohlreich MM, Detke MJ, Walker DJ, Chappell AS, Arnold LM (http://www.ncbi.nlm.nih.gov/pubmed/18395345), states the study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia. The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day).
The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, P<0.001] and PGI-I [2.89 vs 3.39, P=0.004]) and at 6 months (change in BPI [-2.26 vs -1.43, P=0.003] and PGI-I [2.93 vs 3.37, P=0.012]). Compared with placebo, treatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without a major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures.
PMID: 18395345 [PubMed – in process]
(i) Leventhal, LJ. “Management of fibromyalgia.” Annals of Internal Medicine. 1999; 131: 850-858. (ii) Arnold, L, et al. “Family Study of Fibromyalgia.” Arthritis & Rheumatism. 2004; 50(3): 944-952. (iii) Bennett, Robert M., et al. “An Internet Survey of 2,596 People with Fibromyalgia.” BMC Musculoskeletal Disorders. March 9, 2007. 8:27. (iv) Lawrence, et al. “Estimates of the Prevalence of Arthritis and Other Rheumatic Conditions in the United States.” Arthritis and Rheumatism.