Duloxetine in the Treatment of Stress Urinary Incontinence

Abstract

This manuscript reviews the pharmacodynamics and pharmacokinetics of duloxetine and its efficacy and safety in women with stress urinary incontinence. Duloxetine is a selective inhibitor of neuronal serotonin and norepinephrine uptake which increases urethral striated muscle activity and bladder capacity. Duloxetine is readily absorbed and extensively metabolized; cytochrome P450 1A2 (CYP1A2) inhibiting drugs can markedly increase duloxetine exposure. The clinical efficacy of duloxetine has consistently been demonstrated in several randomized, double-blind studies in women with moderate-to-severe stress urinary incontinence, but the additional benefit relative to placebo was moderate. Duloxetine treatment is frequently associated with adverse events such as nausea, dry mouth, fatigue, insomnia and constipation, but serious adverse events are rare. Therefore, duloxetine appears suitable for the treatment of stress urinary incontinence.

Safety and tolerability of duloxetine in women with stress urinary incontinence

“…However, only 3 (2 men and 1 woman) of 4719 duloxetine‐treated patients discontinued treatment because of obstructive voiding symptoms in a meta‐analysis of nine studies in patients with depression and four studies in patients with SUI; acute urinary retention requiring catheterisation was not observed in any patient 18 . This is in line with the proposed mechanism of action, where duloxetine works mainly as an enhancer of endogenous glutamate effects and hence only during the storage phase of the micturition cycle 23,24 …”

“…Therefore, it can be assumed that the adverse events associated with duloxetine treatment are largely related to its mechanism of action at the molecular level, i.e. a mixed inhibition of neuronal serotonin and noradrenaline reuptake 23,24 …”

“…a mixed inhibition of neuronal serotonin and noradrenaline reuptake. 23,24 Adverse events leading to study discontinuation were observed in 15-24% of duloxetine-treated women compared with 2-5% of women on placebo. 7-10 Specific numbers for individual adverse effects are shown in Table 1.…”

Clinical pharmacology of functional disorders of the urogenital system

“…Unfortunately, there is no universal agreement what these safety standards need to be. For example, the selective serotonin/noradrenaline uptake inhibitor duloxetine [2] and the selective serotonin uptake inhibitor dapoxetine [3] have been licensed in Europe for the treatment of stress urinary incontinence and premature ejaculation, respectively, whereas the US regulatory authorities have refused such authorization based upon the benefit/risk profiles of these drugs (of note, duloxetine is registered in the US for two non‐urological indications). Apparently, the scientific and regulatory communities in various parts of the world have not yet agreed what establishes acceptable benefit/risk profiles for such drugs, indicating that the scientific basis for such statements remains too weak.…”

“…Another aspect related to preferential drug action in target tissue vs. other organ systems relates to brain penetration of drugs used in functional urology. While this may be desirable or even required with some drugs such as duloxetine [2] or dapoxetine [3], it is considered unnecessary or even undesirable for others such as α 1 ‐adrenoceptor or muscarinic receptor antagonists. One study in this volume compares factors related to brain penetration of various anti‐muscarinic OAB drugs [10].…”