Switching to Duloxetine Remits Ziprasidone – Associated Urinary Incontinence and Improves Neuropsychiatric Behavior in Dementia: Possible Relationship of Incontinence to 5HT2 Receptor Blockade

Objectives: Urinary incontinence arising in dementia lowers patient quality of life, predicts caregiver burden and nursing home placement, and predisposes to adding additional medicines that can further impair cognition, behavior, and function. An understanding of incontinence pharmacology can help the clinician predict and manage this adverse event in treating patients with dementia. Experimental Design: Case report. Principal Observations: We encountered a patient with Alzheimer’s disease and vascular dementia who developed urinary incontinence and parkinsonism when ziprasidone was added to the regimen for behavioral concerns. When he was switched to duloxetine, the incontinence and parkinsonism resolved whereas improvements in perseveration, irritability, paranoia, and agitation persisted. Conclusions: While a pharmacokinetic explanation is unlikely, the best evidence suggests that ziprasidone-mediated serotonin 5HT2 receptor blockade may explain the reversible incontinence, with an adrenergic alpha-1 receptor mechanism considered to be less likely. Patients on 5HT2 antagonist drugs, including atypical antipsychotics, should be observed for incontinence. In the event of incontinence developing in the context of these agents, duloxetine may represent a potential pharmacological alternative in some cases. Duloxetine may improve neuropsychiatric symptoms in dementia through its effects on serotonin, norepinephrine, and frontal dopamine. Psychopharmacology Bulletin. 2009;42(3):99–105.