piperidines and Urinary-Incontinence--Urge

To investigate the safety and efficacy of litoxetine, a serotonin reuptake inhibitor, in treating urinary incontinence (UI) and mixed urinary incontinence (MUI).. Two randomized, double-blind, placebo-controlled clinical trials (RCT1 and RCT2) were conducted. RCT1, which included 196 women aged 18-75 with MUI randomized 1:1:1:1 to receive 10, 20, or 40 mg litoxetine or placebo orally twice daily (BID) for 12 weeks, investigated the efficacy (including changes in patient reported outcomes) and safety of litoxetine compared to placebo. RCT2, which included 82 men and women aged 18-70 with any UI type randomly assigned 2:1 to receive 30 mg litoxetine or placebo orally BID for 8 weeks including a 2 week dose titration period, investigated the safety (including psychiatric safety) and efficacy of litoxetine compared to placebo. Efficacy was measured as the change in number of incontinence episodes per week and assessed using an analysis of covariance with missing data imputed by Predictive Mean Matching. Safety was assessed by adverse events (AEs) and physical examinations and analyzed using descriptive statistics.. The 30-mg and placebo groups in RCT2 showed no difference in frequency of AEs, and litoxetine reduced the number of incontinence episodes per week compared to placebo. Although RCT1 suffered an unexpectedly high placebo response, and therefore did not meet the primary efficacy endpoint, 71% of participants receiving 40 mg litoxetine reported a clinically meaningful improvement in the King's Health Questionnaire.. Litoxetine may be a safe, effective and well-tolerated treatment for patients with UI.

Topics: Double-Blind Method; Female; Humans; Male; Piperidines; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Urge

Mixed mood states in bipolar disorder are difficult to treat and when present indicate worse illness trajectories. Several medications are US Food and Drug Administration approved to treat mixed episodes; however, the clinical trials have been short term and rarely reported depression response.. We conducted a 5-month open-label trial examining the tolerability and efficacy of iloperidone for bipolar disorder mixed episodes.. Mania and depression scores significantly improved over the course of the study for study completers (ie, 60%-68% improvement for manic symptoms and 41%-49% for depression symptoms). Improvements were observed early in the trial and after adjusting for concomitant medication effects. The average daily dose in completers was 15 mg. Thirty-nine percent (12/31) of the eligible sample discontinued early because of adverse effects. The adverse events most commonly associated with withdrawal were increased heart rate/palpitations (n = 5 of 12) and urinary incontinence/intense urge to urinate (n = 3 of 12).. In a subset of patients, iloperidone provides relief for classic manic, depression, and irritability symptoms associated with mixed episodes in a long-term trial. Adverse effect profiles are likely to be a major factor contributing to individualized medication use.

Topics: Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Bipolar Disorder; Female; Humans; Isoxazoles; Male; Piperidines; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Urge; Young Adult