Duloxetine for Stress Urinary Incontinence
Mechanism of action
Duloxetine is a serotonin and noradrenaline reuptake inhibitor (SSRI), which leads at the urinary tract to an increase in bladder capacity and to an increase in muscle tone of the striated sphincter muscle of the bladder (Thor and Donatucci, 2004).
Urological Indications for Duloxetine:
Duloxetine is most commonly used for the treatment of depressive disorders and generalized anxiety disorders. Duloxetine is in addition approved in Europe for the treatment of stress urinary incontinence of women, while it failed approval in the United States due to security concerns (see side effects). Duloxetine may achieve a reduction of incontinence episodes by 50–60% vs. 20–40% in the placebo group (Mariappan et al, 2007). The combination of duloxetine and pelvic floor exercises leads to improved results. Duloxetine is not approved for the treatment of male stress urinary incontinence, but it is somehow effective and sometimes used as off-label treatment (Cornu et al, 2004).
Pharmacokinetics of duloxetine:
Hepatic inactivation and renal excretion of inactive metabolites. Half life time is 12 hours. Liver insufficiency prohibits the administration of duloxetine. In renal insufficiency, dosage adjustment is necessary below a GFR of 30 ml/min.
Side Effects of Duloxetine
Nausea, fatigue, insomnia, dry mouth, constipation, diarrhea, dizziness, headache, blurred vision, restlessness, hyponatremia, liver toxicity, increased risk of suicide. The risk of severe liver toxicity or suicide is debatable.
Interactions of Duloxetine:
Do not combine Duloxetine with MAO inhibitors or SSRI (serotonin reuptake inhibitors), there is a relevant risk for a serotonin syndrome. Do not combine duloxetine with ciprofloxacin, enoxacin or other inhibitors of CYP1A2.
Contraindications for Duloxetine:
- Hepatic insufficiency
- Severe renal insufficiency
- Uncontrolled hypertension
- Therapy with MAO inhibitors or SSRI.
- Pregnant and nursing women, children, men.
- Caution in patients with mania, bipolar disorder, epilepsy, glaucoma, anticoagulation or platelet function disorders.
- Caution during concomitant administration of sedatives, alcohol, opiates.
Dosage of duloxetine:
20 mg p.o. twice a day (1-0-1). After 2 weeks, increase the dosage to 40 mg 1-0-1. If the medication with duloxetine is to be stopped, the dosage should be decreased slowly over two weeks.
Brand names of duloxetine:
Duloxetine is sold under various brand names like Cymbalta, Ariclaim, Xeristar, Yentreve and Duzela.
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- Thor, K. B. & Donatucci, C.
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system control of the lower urinary tract: new pharmacological approaches
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- Duloxetine, a serotonin and noradrenaline reuptake inhibitor
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Eur Urol, 2007, 51, 67-74.