Cymbalta (Duloxetine)

Cymbalta (Duloxetine) is a new antidepressant, indicated for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD) (approved in February 2007), and for the management of diabetic peripheral neuropathic pain (DPNP). Cymbalta offers relief from both the emotional and painful physical symptoms associated with depression.

On June 2008, Cymbalta was approved for the management of fibromyalgia. And recently, on November 2010, Cymbalta was licensed for chronic musculoskeletal pain.

Cymbalta comes in capsules and can be taken once a day. The target daily dose is 60 mg. It is not recommended for those under 18. Controlled studies indicate a high degree of efficacy, tolerability, and safety for duloxetine in the treatment of major depressive disorder.

Cymbalta side effects
The most common side effects associated with Cymbalta are nausea, dry mouth, constipation, insomnia, dizziness, decreased appetite, fatigue, somnolence, and increased sweating 2. Nausea usually resolves after about 7 days 4. However, insomnia may be persistent 13.

How long does Cymbalta take to work?
For depression, response may vary from person to person. Several weeks are often required for duloxetine to reach its maximum effectiveness. However, improvement in anxious symptoms may occur after 1-2 weeks 15.

• Absorption: Well absorbed. Steady state reached after 3 days.
• Metabolism: Hepatic metabolism by CYP1A2 and CYP2D6 to numerous metabolites.
• Elimination half-life: 12 hours
• Excretion: 70% of duloxetine is eliminated in the urine as metabolites and 20% is excreted in the feces.

• reduces painful physical symptoms of depression 7
• relatively fast onset of antidepressant effect - improvements may be noticed after 2 weeks 8
• lower rate of sexual side effects than the SSRIs 5
• short-term treatment is not associated with weight gain, and may cause weight loss 14
• convenience of once-daily dosing
• low risk of duloxetine emergent hypomania or mania 12

• risk of cardiovascular side effects (increased heart rate and blood pressure, changes in electrocardiogram)3
• high rate of insomnia, which may be a persistant13
• risk of weight gain with long-term use14
• risk of severe withdrawal symptoms1, though you should not change the dosage or stop taking duloxetine without your doctor's approval
• risk of serotonin syndrome when used with serotonergic agents (triptans and some other prescription drugs)
• high cost

• Stress urinary incontinence 6
• Chronic fatigue syndrome

Cymbalta for Fibromyalgia
Fibromyalgia is a perplexing and often disabling disorder, characterized by chronic musculoskeletal pain and tenderness.

Cymbalta was approved by the FDA for the management of fibromyalgia in June 2008. It improves most fibromyalgia symptoms in about 60% of patients 9.

Evidence of the efficacy of duloxetine in fibromyalgia was demonstrated in good-quality randomized multicenter controlled trial, in which duloxetine (60 mg twice daily for 12 weeks) was associated with moderate reductions in the total score on the Fibromyalgia Impact Questionnaire and improvements in quality of life and disability scores. However, significant improvement with duloxetine occurred in the overall population and females only, whereas a benefit was not shown in men 10.

In another randomized placebo-controlled trial more than half of patients treated with Cymbalta (60 mg once or twice daily), responded to treatment after 12 weeks, compared with 33% of those taking a placebo 11. Patients treated with Cymbalta had functional improvements on the Sheehan Disability Scale which measures disability at work, in family life and in social life, that were significantly greater than those of patients taking placebo. Cymbalta 60 mg once or twice daily directly reduced pain (75.7 and 87.5 percent, respectively) more than the indirect effect attributed to improvement in depressive symptoms (24.4 percent and 12.5 percent, respectively). Cymbalta also relieved the pain associated with tender points often associated with fibromyalgia.

Duloxetine is a potent and selective serotonin and norepinephrine reuptake inhibitor, that lacks significant affinity for muscarinic, histamine1, alpha1-adrenergic, dopamine, opiate receptors, and ion channels including Na+ channels.

If you plan to buy Cymbalta or generic Duloxetine you might wish to learn experience of other people using it.

• Cymbalta (Duloxetine) Reviews, Ratings by Patients on DrugLib.com
• Cymbalta user reviews on Drugs.com
• Cymbalta Reviews and success rate on DailyStrength.org
• Askapatient database: Cymbalta (Duloxetine) ratings
• Cymbalta ratings (recommended by 58% of reviewers) on PsychCentral.com
• Cymbalta official website

• 1. Petition to Cymbalta manufacturer, Eli Lilly and Company. PetitionOnline
• 2. Hudson JI, Perahia DG, Gilaberte I, Wang F, Watkin JG, Detke MJ. Duloxetine for depression. BMC Psychiatry. 2007 Aug 28;7(1):43. PubMed
• 3. Wernicke J, Lledo' A, Raskin J, Kajdasz DK, Wang F. An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies. Drug Saf. 2007;30(5):437-55.
• 4. Greist J, McNamara RK, Mallinckrodt CH, Rayamajhi JN, Raskin J. Incidence and duration of antidepressant-induced nausea. Clin Ther. 2004 Sep;26(9):1446-55. PubMed
• 5. Schweitzer I, Maguire K, Ng C. Sexual dysfunction of contemporary antidepressants. Aust N Z J Psychiatry. 2009 Sep;43(9):795-808. PubMed
• 6. van Kerrebroeck P, Abrams P, Lange R, Slack M, Wyndaele JJ, Yalcin I, Bump RC. Duloxetine versus placebo for the European and Canadian women with stress urinary incontinence. BJOG. 2004 Mar;111(3):249-57. PubMed
• 7. Brannan SK, Mallinckrodt CH, Brown EB, Wohlreich MM, Watkin JG, Schatzberg AF. J Psychiatr Res. 2005 Jan;39(1):43-53. PubMed
• 8. Brannan SK, Mallinckrodt CH, Detke MJ, Watkin JG, Tollefson GD. Duloxetine onset of action. J Psychiatr Res. 2005 Mar;39(2):161-72. PubMed
• 9. Littlejohn GO, Guymer EK. Fibromyalgia syndrome: which antidepressant should we choose. Curr Pharm Des. 2006;12(1):3-9. PubMed
• 10. Arnold LM, Lu Y, Crofford LJ et al. A double-blind, multicenter trial comparing duloxetine with placebo in fibromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004;50:2974-84 PubMed
• 11. Arnold LM, Rosen A, Pritchett YL, D'Souza DN, Goldstein DJ, Iyengar S, Wernicke JF. A randomized, double-blind, placebo-controlled trial of duloxetine in women with fibromyalgia with or without major depressive disorder. 2005 Dec 15;119(1-3):5-15. PubMed
• 12. Dunner DL, D'Souza DN, Kajdasz DK, Detke MJ, Russell JM. Is treatment-associated hypomania rare with duloxetine: secondary analysis of controlled trials in non-bipolar depression. J Affect Disord. 2005 Jul;87(1):115-9. PubMed
• 13. Wohlreich MM, Mallinckrodt CH, Prakash A, Watkin JG, Carter WP. Duloxetine for the major depressive disorder. Depress Anxiety. 2007;24(1):41-52. PubMed
• 14. Wise TN, Perahia DG, Pangallo BA, Losin WG, Wiltse CG. Prim Care Companion J Clin Psychiatry. 2006;8(5):269-78. PubMed
• 15. Hirschfeld RM, Mallinckrodt C, Lee TC, Detke MJ. Time course of depression-symptom improvement with duloxetine. Depress Anxiety. 2005;21(4):170-7. PubMed

Last modified: January, 2012