Duloxetine

Duloxetine is a prescription drug for treatment of anxiety, depression, fibromyalgia, and diabetic neuropathy. It was approved in 2002, and is marketed as the active ingredient in specially-designed capsules under the trade names Cymbalta and Xeristar by Eli Lilly and Company.

Uses

Duloxetine is approved for the treatment of major depressive disorder (MDD), peripheral neuropathic pain caused by diabetes, generalized anxiety disorder (GAD), and (in the US), fibromyalgia. The drug is not approved for fibromyalgia in Europe, however.^[1]

How Duloxetine is Taken

Duloxetine is sold in tablet form as Cymbalta with 20, 30, or 60 mg dosage strengths. The capsules are designed to resist degradation by stomach acid and release the active ingredient once they reach the intestines. Capsules are usually taken once a day.

Major Depressive Disorder (MDD)

For MDD, duloxetine is taken at a total dose of 40 mg daily (given as 20 mg twice daily) to 60 mg maximum daily (either 60 mg once daily or 30 mg twice daily). Treatment of MDD remains a challenge, and a recent study has shown that many recently-approved antidepressants (bupropion, duloxetine, mirtazapine, and venlafaxine) offer comparable success rates.^[2]

Diabetic Peripheral Neuropathic Pain

For diabetic peripheral neuropathic pain, duloxetine is taken at a total dose of 60 mg daily given once a day. The drug does not appear to prevent nerve damage; rather, its effects seem to be based on its activity at serotonin and norepinephrine receptors in mediating pain. It tends to increase blood glucose to a small extent, but also tends to improve patients' reported quality of life.^[3]

Generalized Anxiety Disorder (GAD)

For GAD, duloxetine is taken at a total dose of 60 mg once daily. Duloxetine offers improvements in GAD symptoms as well as improvements in reported well-being and quality of life.^[4]

How Duloxetine Works

Duloxetine belongs to a family of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs). Other members of this family include venlafaxine (Effexor XR, Effexor) and sibutramine (Meridia, Reductil). Although the exact mechanism of duloxetine is not precisely known, its actions are believed to be related to its effect on the levels of the neurotransmitters serotonin and norepinephrine in the central nervous system.^[5]

Lab studies have shown that duloxetine is a strong inhibitor of serotonin and norepinephrine reuptake by brain cells. This action would theoretically raise levels of serotonin and norepinephrine in the spaces between brain cells (called "synapses"). Increased levels of serotonin and norepinephrine in the synapses is believed to alleviate the symptoms of depression and anxiety.

How the Body Affects Duloxetine

Duloxetine is well absorbed with peak circulating levels occurring at 6 hours post-dosing (on an empty stomach).

The liver enzymes CYP2D6 and CYP1A2 metabolize duloxetine into its primary metabolites: 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate.

Approximately 70% of the original dose is excreted in the urine as metabolites. About 20% is excreted in the feces.

Side Effects

The most common side effects observed with duloxetine use are:

• Nausea
• Vomiting
• Constipation
• Diarrhea
• Dry mouth
• Dyspepsia (indigestion)
• Loose stools
• Fatigue
• Asthenia (feelings of weakness)
• Fever
• Nasopharyngitis (common cold symptoms)
• Decreased appetite
• Anorexia (loss of appetite)
• Muscle cramp
• Myalgia (muscle aches)
• Somnolence (sleepiness)
• Headache
• Dizziness
• Tremor
• Insomnia
• Frequent daytime urination (pollakiuria)
• Erectile Dysfunction
• Cough
• Sore throat
• Increased sweating

Risks and Precautions

As with many other antidepressants, persons taking duloxetine may develop suicidal thoughts, especially when the drug is first started or when the dose is changed.^[6]

Drug Interactions

Since the liver enzymes CYP1A2 and CYP2D6 are responsible for duloxetine metabolism, concurrent use of CYP1A2 inhibitors (such as fluvoxamine and quinolone antibiotics) and CYP2D6 inhibitors (such as paroxetine, fluoxetine, and quinidine) with duloxetine is to be avoided.

Duloxetine must not to be used with any MAO inhibitors (MAOIs) nor with any anti-migraine medications called triptans.

Effectiveness

Dr. Sidney Kennedy, Psychiatrist-in-Chief at the University Health Network in Toronto said in a statement regarding a study of duloxetine in depression:^[7]

"Remission is the gold standard for anti-depressant treatment... Over 80% of patients in this study who responded to Cymbalta were still taking it after one year and were virtually free of symptoms..."

References

1. ↑ Scrip World Pharmaceutical News: CHMP delivers negative opinion on duloxetine in fibromyalgia
2. ↑ Hansen RA, Gartlehner G, Lohr KN, Gaynes BN, Carey TS. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005 Sep 20;143(6):415-26. Abstract | PDF
3. ↑ Smith T, Nicholson RA. Review of duloxetine in the management of diabetic peripheral neuropathic pain. Vasc Health Risk Manag. 2007;3(6):833-44. Abstract | Full Text | PDF
4. ↑ Müller N, Schennach R, Riedel M, Möller HJ. Duloxetine in the treatment of major psychiatric and neuropathic disorders. Expert Rev Neurother. 2008 Apr;8(4):527-36. Abstract
5. ↑ Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ. Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol. 2008 May;23(3):161-9. Abstract
6. ↑ Salem BA, Karam EG. Duloxetine and suicide attempts: a possible relation. Clin Pract Epidemol Ment Health. 2008 Jun 11;4:18. Abstract | Full Text | PDF
7. ↑ Boehringer Ingelheim news release: Sidney Kennedy interview

External Links

• Drug Digest
• FDA: Patient Information Sheet
• Drugs.com
• Rx List