Stress urinary incontinence duloxetine

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

Guay DRP. Duloxetine for management of stress urinary incontinence. Am J Geriatr Pharmacother 2005 3 25-38. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

Geriatric Considerations - Summary Compared to placebo, duloxetine is effective for the treatent of depression and painful diabetic neuropathy Few head-to-head studies are available comparing duloxetine to other agents in the treatment of depression or painful neuropathy. Because this agent may increase urethral sphincter activity, it is now being assessed as an agent for the treatment of stress urinary incontinence. This same property may increase the risk of urinary retention, although this has not been well documented. Duloxetine has not been well studied with respect to falls. 

The SNRIs include venlafaxine, its metabolite desvenlafaxine, and duloxetine. Another SNRI, milnacipran, is in late clinical trials in the USA but has been available in Europe for several years. In addition to their use in major depression, other applications of the SNRIs include the treatment of pain disorders including neuropathies and fibromyalgia. SNRIs are also used in the treatment of generalized anxiety, stress urinary incontinence, and vasomotor symptoms of menopause. 

Zinner NR. Duloxetine a serotonin-noradrenaline re-uptake inhibitor for the treatment of stress urinary incontinence. Expert Opin Investig Drugs 2003 ... 

Duloxetine (LY-248686), (S)-(-i-)-N-methyl-3-(l-naphthyloxy)-3-(2-thienyl)propyl-amine, is expected to be not only a new potent antidepressant but also a NE (norepinephrine) reuptake inhibitor, a 5-HT (serotonin) reuptake inhibitor, and a new treatment drug for stress urinary incontinence [18]. In order to produce an enantiopure key intermediate for the synthesis of the (S)-amine, the Eli Lilly group proposed various strategies [19]. As a result, they selected the enantioseparation of racemic 3-(dimethylamino)-l-(2-thienyl)propan-l-ol with (S)-mandelic acid by diastereomeric salt formation as the most economic and suitable process for industrial-scale production with efficient supporting techniques such as the racemization of the antipode and recycling the recovered materials [20]. However, in the process of demethylation for the preparation of (S)-Duloxetine from (S)-3-(di-methylamino)-l-(2-fhienyl)propan-l-ol, there are some critical problems, such as low yield and considerable decomposition to give impurities. Thus, a direct synthesis of (S)-Duloxetine starting from (S)-3-(methylamino)-l-(2-thienyl)propan-l-ol is expected to be a new route for the production of (S)-Duloxetine. 

Trospium is a quaternary amine long used in Europe and approved recently for use in the United States for treatment of overactive bladder. It has been shown to be as effective as oxybutynin with better tolerability. Solifenacin is newly approved for overactive bladder with a favorable efficacy side effect ratio. Stress urinary incontinence has been treated with some success with duloxetine (Yentreve), which acts centrally to influence serotonin and norepinephrine levels. 

Overactive urinary bkuMer disease can be successfully treated with muscarinic antagonists, primarily tolterodine and trospium chloride, which lower intravesicular pressure, increase capacity, and reduce the frequency of contractions by antagonizing parasympathetic control of the bladder. Oxybu-tynin is used as a transdermal system (oxytrol) that delivers 3.9 mg/day and is associated with a lower incidence of side effects than the oral immediate- or extended-release formulations. Tolterodine is metabolized by CYP2D6 to a 5-hydroxymethyl metabolite since this metabolite possesses similar activity to the parent drug, variations in CYP2D6 levels do not affect the duration of drug action. Trospium is as effective as oxybutynin, with better tolerability. Solifenacin is newly approved for overactive bladder with a favorable efficacy side effect ratio. Stress urinary incontinence has been treated with some success with duloxetine (YENTREVE), which acts centrally to influence 5-HT and NE levels. 

Corynomycollc acid isolated from the cell walls of Cor-ynebacterium sp. or related organisms exhibit immunostimu-lant properties.Duloxetine is a serotonin-norepinephrine reuptake inhibitor used in major depressive disorder, general anxiety disorder, stress urinary incontinence,diabetic peripheral neuropathy, fibromyalgia,and chronic musculoskeletal pain associated with osteoarthritis and chronic lower back pain. Fluoxetine is a serotonin-uptake inhibitor used as an antidepressant and for treatment of anxiety, alcoholism, and bulimia. " ... 

Lin AT et al Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan A double-blind, randomized, placebo-controlled trial. BMC Urol 2008 8 2. [PMID 18221532]... 

Duloxetine (when approved for treatment of urinary in- continence), a-adrenergic receptor agonists, and topical (vaginal) estrogens (alone or together) are the therapies of choice in urethral underactivity (stress incontinence). 

OTHER THERAPEUTIC USES OE THESE DRUGS The various antidepressant agents have found broad utility in other disorders that may not be related psychobiologicaUy to the mood disorders. Current applications include rapid but temporary suppression of enuresis with low (e.g., 25 mg) pre-bedtime doses of tricyclic antidepressants, including imipramine and nortriptyline, by uncertain mechanisms in children and in geriatric patients, as well as a beneficial effect of duloxetine on urinary stress incontinence. Antidepressants have a growing role in attention-deficit/hyperactivity disorder in children and adults, for which imipramine, desipramine, and nortriptyline appear to be effective, even in patients responding poorly to or who are intolerant of the stimulants (e.g., methylphenidate). Newer NE selective reuptake inhibitors also may be useful in this disorder atomoxetine is approved for this application. Utility of SSRIs in this syndrome is not established, and bupropion, despite its similarity to stimulants, appears to have limited efficacy. 

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