Clozapine-induced urinary incontinence: incidence and treatment with ephedrine

Treatment with the atypical antipsychotic drug clozapine appears to be associated with an increased incidence of urinary incontinence (UI). We posited that the potent anti-alpha-adrenergic effects of clozapine were involved, and hence that an alpha-adrenergic agonist would reduce UI. We tested this hypothesis by using ephedrine, an approved alpha-adrenergic agonist.

Fifty-seven inpatients with schizophrenia or schizoaffective disorder (DSM-IV) who met the Kane criteria for being treatment refractory were treated with clozapine (75-900 mg/day). Patients who developed UI were then openly treated with ephedrine in increasing doses until UI was attenuated or a dose of 150 mg/day was attained.

Seventeen patients developed UI as evidenced by either urine-stained sheets/clothing or direct patient reports. In 2 cases, the UI was sufficiently severe that adult diapers had to be used. Comparison of patients who developed UI and those who did not showed that UI was associated with female gender and with concomitant treatment with typical antipsychotic drugs. One patient was treated with a behavioral program, but the remaining 16 patients were treated with ephedrine. Ephedrine treatment was very effective, with 15/16 patients showing improvement within 24 hours after reaching maximum ephedrine dosage. Twelve of 16 (including the 2 most severe) eventually had a complete remission of their UI. In the remaining 4 patients, 3 had a reduction in the frequency of UI and 1 showed no response. These benefits have been maintained over the course of 12 months of subsequent treatment for several patients. There were no side effects associated with the use of ephedrine nor were there any changes in neuropsychiatric status.

Ephedrine appears to be a safe and effective treatment clozapine-associated UI. By inference, it is likely that clozapine may cause UI via its anti-alpha-adrenergic properties.