Duloxetine Delayed-Release Capsules (Cymbalta®)
Pharmacology Update
Duloxetine Delayed-Release Capsules (Cymbalta®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
Duloxetine is the first serotonin norepinephrine reuptake inhibitor (SNRI) to be approved for the treatment of fibromyalgia. It joins pregabalin as one of only two drugs approved for this indication. Duloxetine was originally approved in 2004 for major depressive disorder.
Indication
In addition to approval for the management of fibromyalgia, duloxetine is also approved for major depressive disorder, generalized anxiety disorder, and diabetic peripheral neuropathy.1
Dosage
The recommended dose for fibromyalgia is 60 mg once daily. Treatment should be initiated at 30 mg daily for one week before escalating to 60 mg daily.1
Duloxetine is supplied as 20 mg, 30 mg, and 60 mg delayed-release capsules.
Potential Advantages
Duloxetine appears to be effective in fibromyalgia with or without major depressive disorder.2,3 It also shows an improvement in Hamilton Depression Rating Scale compared to placebo.
Potential Disadvantages
Most common adverse events include nausea, dry mouth, constipation, anorexia, diarrhea, sleepiness, nervousness, increased sweating, and agitation.1 Duloxetine, as with other antidepressants, may increase the risk of suicidal thinking and behavior. Hepatic failure, sometimes fatal, and risk of bleeding events have been reported.1
Comments
In clinical trials, duloxetine, has shown efficacy in patients (predominately women) meeting American College of Rheumatology criteria for fibromyalgia. Primary efficacy was assessed as reduction of the Brief Pain Inventory. About 40% of patients achieved a 50% reduction compared to about 20% for placebo.1,3 The degree of pain reduction may be greater in patients with major depressive disorder. However the improvement in pain is independent of the drug's effect on depression. Secondary endpoints such as sleep and quality of life were generally improved. There was no efficacy difference between 60 mg daily compared to 60 mg twice daily but more adverse events were associated with the higher dose. There are currently no comparative trials between duloxetine and pregabalin or other agents (eg, tricyclic antidepressants). In a similar study, about 30% of patients on pregabalin (450 mg/day) showed a 50% pain reduction compared to 13% for placebo.5 While sleep and quality of life were improved, depression scores were not improved with pregabalin. Pregabalin has a different adverse event profile than with duloxetine with dizziness, somnolence, headache, dry mouth, and peripheral edema most common.
Clinical Implications
Fibromyalgia is a chronic condition characterized by pain, stiffness, sleep disturbance, and muscle fatigue. These patients appear to be more sensitive to peripheral stimuli (ie, hyperalgesia and allodynia).4 It is also associated with anxiety, cognitive disturbance, and depression. The overall prevalence is about 2% and more common in women. Pharmacotherapy has included a variety of drugs from different pharmacological classes such antidepressants (eg, tricyclic antidepressants, SNRIs), anticonvulsants (eg, gabapentin, pregabalin), dopamine receptor agonists (eg, pramipexole), and analgesics (eg, tramadol).4,6 Duloxetine offers a new option for the treatment of fibromyalgia and accompanying depression.
References
1. Cymbalta Product Information. Eli Lilly and Company. June 2008.
2. Arnold LM, et al. Arthritis Rheum. 2004;50:2974-84.
3. Arnold LM, et al. Pain. 2005;119:5-15.
4. Staud R. Exper Opin Pharmacother. 2007;8:1629-1642.
5. Crofford LJ, et al. Arthritis Rheum. 2005;52:1264-1273.
6. Rooks DS. Curr Opin Rheumatol. 2007;19:111-1117.
Duloxetine is the first serotonin norepinephrine reuptake inhibitor (SNRI) to be approved for the treatment of fibromyalgia.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.