1 Carseview centre, 4 Tom McDonald Avenue, Dundee, UK. DD2 1NH

2 Professor of Psychiatry and Psychotherapy, University of Bonn, Germany


Clozapine is an effective antipsychotic medication licenced for the management of treatment resistant schizophrenia. Due to its non-selective pharmacology, it has a broad range of side effects. Nocturnal enuresis secondary to the use of clozapine has been documented in the literature but may be overlooked, the link between drug and symptom being clinically unnoticed. Patients may not mention urinary symptoms due to supervening psychosis, co-existing symptomatology, embarrassment or shame. By raising awareness of the phenomenon, early recognition and patient support may improve compliance with clozapine medication, and consecutively, overall mental health. Consequently, this systematic review investigates the prevalence of nocturnal enuresis secondary to clozapine use.

A literature search on clozapine and nocturnal enuresis was used to identify the relevant papers. Papers providing the prevalence data on Clozapine associated nocturnal enuresis were selected for data extraction.

47 papers were initially identified. Eight papers focused on the prevalence of clozapine associated nocturnal enuresis (CANE). Point prevalence (nocturnal enuresis at the time of assessment), 1-month prevalence and episode prevalence (nocturnal enuresis since beginning of clozapine) were given. Papers included patients with schizophrenia, schizoaffective disorder, bipolar affective disorder and psychotic depression, taking clozapine medication. The prevalence of CANE ranged from 10–42%. Point prevalence was 21–27%, 1-month prevalence was 10–39% and episode prevalence was 15–42%. Clozapine was more likely to cause nocturnal enuresis compared to other psychotropic medication.

The prevalence of CANE may be greater than previously thought. However, in order to determine an accurate prevalence of clozapine associated nocturnal enuresis, larger studies with strict inclusion criteria, common definition of diagnosis and prevalence are required. By establishing an accurate prevalence, physician awareness can be improved, and patients can becounselled on the risk of developing the side effect, thus improving early identification and reducing discontinuation rates.