Bethanechol and Aripiprazole for the management of refractory urinary incontinence in a patient on Clozapine

To the Editor

Urinary incontinence (UI) frequently complicates Clozapine therapy (Fuller et al., 1996). We present the complex case of a 47-year-old woman with treatment-resistant schizophrenia. Her medical history included Hepatitis C, HIV, fatty liver disease, obesity, epilepsy (grand-mal type with no seizures in the past 10 years), polypharmacy, nulliparity, cigarette smoking and a recent episode of medication-induced acute renal failure. Schizophrenia was diagnosed at the age of 22, characterised by disorganisation, delusions and auditory hallucinations with commands to harm herself, resulting in serious self-harm and suicide attempts. Previous unsuccessful medication trials included Olanzapine, Quetiapine, Ziprasidone and Lithium. Clozapine was commenced in 2010, and she was eventually stabilised on a regimen of Clozapine 200 mg nightly (serum level 290 ug/L) and Risperidone 2 mg twice daily. This regimen had resulted in complete resolution of her delusions and hallucinations, and modest improvements in disorganisation. Un-fortunately, since starting Clozapine, she developed UI with frequent large volume daytime and nocturnal episodes. She was not experiencing constipation or seizures. Urodynamic studies were requested and these indicated a stable bladder with no evidence of overactivity. The patient was distressed by the UI, but preferred to continue the Clozapine due to its efficacy.

Non-pharmacological measures were unhelpful, despite assistance from a support worker. The anticholinergic drug Oxybutynin was then introduced, without success. After case discussion, her urologist suggested a trial of Bethanechol, a cholinergic agent, at 10 mg three times a day. Both daytime and nocturnal UI subsequently fell in volume and frequency. Bethanechol was well tolerated, with no change in her sialorrhoea. Subsequently, the Risperidone was cross-titrated to Aripiprazole 20 mg daily to address her adverse metabolic parameters and abulia. At this point, her UI improved markedly, with only one or two reported episodes monthly. The patient then stopped taking Bethanechol for some weeks as part of her disorganised behaviour. Her UI returned, and then resolved upon re-commencement.

Clozapine-induced UI is likely to be multifactorial (Barnes et al., 2012; Fuller et al., 1996; Lee and Kim, 2010), and both anticholinergic and cholinomimetic effects have been implicated. Hence, the cholinergic agent Bethanechol could have a useful place in management. Lee and Kim (2010) have suggested that Aripiprazole may also be of benefit due to its partial dopamine agonist activity. We suggest that both Bethanechol and Aripiprazole may be effective pharmacological measures to consider in the management of persistent Clozapine-induced UI after non-pharmacological measures have failed.