David R P Guay1. 1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA. guayx001@umn.edu
Abstract
OBJECTIVE: The aim of this article was to review data regarding the efficacy and tolerability of duloxetine, a selective serotonin (5-HT)-norepinephrine (NE) reuptake inhibitor that has received US Food and Drug Administration marketing approval for the treatment of major depressive disorder and painful diabetic neuropathy, and that has been investigated as a treatment for stress urinary incontinence. METHODS: A MEDLINE/PubMed search was conducted to identify English-language study reports. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts (search terms included duloxetine, thiophenes, serotonin uptake inhibitors, adrenergic uptake inhibitors, and stress urinary incontinence). Additional references were obtained from the bibliographies of these sources. Data for the period from 1986 through January 2005 were reviewed. RESULTS: All in vitro and in vivo studies of duloxetine were included. Because both 5-HT and NE are involved in the maintenance of urinary continence, duloxetine may have a role in the treatment of urinary incontinence. Duloxetine is primarily eliminated via metabolism, with < 1% of the parent compound excreted via urine. Duloxetine QD or BID has been found to be significantly superior to placebo in reducing incontinence episode frequency (P < 0.001 to P < 0.05), increasing the interval between micturitions (P < 0.001 to P = 0.004), and improving the condition as measured by patient self-report (P < 0.001 to P = 0.028) and incontinence quality-of-life scores (P = 0.002 to P = 0.03). The most problematic adverse events are nausea, dry mouth, constipation, dizziness, and insomnia. CONCLUSIONS: Although statistically superior to placebo in efficacy trials, the clinical effects of duloxetine therapy on incontinence are small, suggesting that any benefits to the patient would be modest and must be weighed against the drug's adverse event profile. No comparative efficacy/tolerability data with alpha-receptor agonists (eg, pseudoephedrine) are available. On the basis of available data, duloxetine is a modest, but welcome, advance in the pharmacotherapeutic management of stress urinary incontinence.
OBJECTIVE: The aim of this article was to review data regarding the efficacy and tolerability of duloxetine, a selective serotonin (5-HT)-norepinephrine (NE) reuptake inhibitor that has received US Food and Drug Administration marketing approval for the treatment of major depressive disorder and painful diabetic neuropathy, and that has been investigated as a treatment for stress urinary incontinence. METHODS: A MEDLINE/PubMed search was conducted to identify English-language study reports. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts (search terms included duloxetine, thiophenes, serotonin uptake inhibitors, adrenergic uptake inhibitors, and stress urinary incontinence). Additional references were obtained from the bibliographies of these sources. Data for the period from 1986 through January 2005 were reviewed. RESULTS: All in vitro and in vivo studies of duloxetine were included. Because both 5-HT and NE are involved in the maintenance of urinary continence, duloxetine may have a role in the treatment of urinary incontinence. Duloxetine is primarily eliminated via metabolism, with < 1% of the parent compound excreted via urine. Duloxetine QD or BID has been found to be significantly superior to placebo in reducing incontinence episode frequency (P < 0.001 to P < 0.05), increasing the interval between micturitions (P < 0.001 to P = 0.004), and improving the condition as measured by patient self-report (P < 0.001 to P = 0.028) and incontinence quality-of-life scores (P = 0.002 to P = 0.03). The most problematic adverse events are nausea, dry mouth, constipation, dizziness, and insomnia. CONCLUSIONS: Although statistically superior to placebo in efficacy trials, the clinical effects of duloxetine therapy on incontinence are small, suggesting that any benefits to the patient would be modest and must be weighed against the drug's adverse event profile. No comparative efficacy/tolerability data with alpha-receptor agonists (eg, pseudoephedrine) are available. On the basis of available data, duloxetine is a modest, but welcome, advance in the pharmacotherapeutic management of stress urinary incontinence.
Authors: Xuan Qin; John M Hakenjos; Kevin R MacKenzie; Mercedes Barzi; Hemantkumar Chavan; Pranavanand Nyshadham; Jin Wang; Sung Yun Jung; Joie Z Guner; Si Chen; Lei Guo; Partha Krishnamurthy; Karl-Dimiter Bissig; Stephen Palmer; Martin M Matzuk; Feng Li Journal: Drug Metab Dispos Date: 2021-11-16 Impact factor: 3.922