Nocturnal Enuresis is an Under-recognised Side Effect of Clozapine: Results of a Systematic Review
and | Nov 12, 2018
About this article
Published Online: Nov 12, 2018
Page range: 21 - 30
Received: Aug 28, 2018
Accepted: Aug 28, 2018
DOI: https://doi.org/10.2478/gp-2018-0007
Keywords
© 2019 Niku Dhillon, Reinhard Heun. published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Figure 1
Description of studies providing episode and point prevalence of clozapine associated nocturnal enuresis
| Authors (year) | Country | Assessment of prevalence | Diagnostic tool | Sample | Diagnoses included | Gender | Mean Age | Clozapine dose | Concurrent Medications | Prevalence of CANE | Conclusion | Limitations | Bias |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Centorrino, Baldessarini, Kando et al 1994 | USA | Cross sectional | Patient interview conducted by a psycho- pharmacologist 43 item modified Systematic assessment for treatment-emergent events scale Markowitz etal. (1987] | 44 outpatients receiving weekly clozapine monitoring | Schizophrenia, schizoaffective disorder, BAD, psychotic depression | 75% male | 37 Range 18-65 | Mean 294mg/day Range: 12.5-900mg | Benzodiazepines, lithium, antidepressants | 27% point prevalence | High frequency of CANE in those taking clozapine | Did not investigate other causes of CANE. Did not investigate if NE was present prior to initiation of antipsychotic | Small sample size |
| Long, West, Siddique et al 2015 | United Kingdom | Cross sectional | Patient interview Unvalidated six-item questionnaire. Information received from case notes or from the care coordinator | 72 women in a secure psychiatric setting taking clozapine | Schizophrenia, schizoaffective depression, personality disorders, PTSD | 100% female | 35.6 Range 18-70 | Not specified | Not specified | 21% point prevalence | CANE and urinary incontinence (Ul]are prevalent amongst those taking psychotropic medication | Other causes of CANE not investigated. Did not investigate if NE was present prior to initiation of antipsychotic | Recall bias Selection bias. Limited generalisability |
| Jeong, Kim, Ann et al 2008 | Korea | Retrospective assessment of 1 month prevalence of CANE | Patient interview.
7-item International prostate symptom score questionnaire. | 101 outpatients taking a stable dose of clozapine | Schizophrenia, bipolar disorders, major depression, OCD | 60% male | 31.1 Range 17-52 | Mean dose 304.2mg | Not specified | 10% 1 month point prevalence | Lower urinary tract symptoms are prevalent in those taking clozapine. LUTS worsened by 11% over subsequent 2 years | Did not investigate if NE was present prior to initiation of antipsychotic. Did not specify if CANE changed over the 2 year period | Recall bias Participants aware of the study aims |
| Yusufi Mukherjee, Flanagan et al 2007 | United Kingdom | Retrospective assessment of 1 month prevalence of CANE | Patient interview. 35 item questionnaire using the Antipsychotic non-neurological side effects rating scale. Ohlsenetal. [2008] | 103 outpatients receiving clozapine monitoring in one trust | Schizophrenia or schizoaffective disorder | 69% male | 39.3 Range 18-65 | Mean 456mg/day | Mood stabiliser anticholinergics, antidepressant, second antipsychotic, anxiolytic or hypnotic | 39% 1 month point prevalence | Clozapine plasma levels were weakly correlated with presence and severity of side effects. Direct questioning required to illicit side effects | Did not investigate other causes of CANE. Did not investigate if NE was present prior to initiation of antipsychotic | Study design bias |
| Bhirud, Shah 2004 | India | Retrospective | Patient interview. Asked for the presence of NE since starting clozapine | 100 consecutive patients on clozapine in a hospital setting | Schizophrenia and bipolar affective disorder | Not specified | Not specified | 50-100+mg | Not specified | 15% episode prevalence since starting clozapine | CANE started within 3 weeks of clozapine initiation or when dose was increased | Did not investigate other causes of CANE. Did not investigate if NE was present prior to initiation of antipsychotic | Recall bias Reporting bias |
| Harrison-WooLrych, Skegg, Ashton et al 2011 | New Zealand | Retrospective | Patient interview conducted by medical or nursing staff Questionnaire based on the Intensive medicines monitoring programme. Harrison-Woollrych et al. [2007] | 91 patients from one urban district taking clozapine | Schizophrenia, affective disorders, neurotic disorders and other | 60% male | 39.1 Range 18-64 | Not specified | 62% of patients taking clozapine took other medications that act on the central nervous system | 20.7% of new cases of NE since starting treatment | Episode prevalence of CANE is one fifth after varying lengths of treatment | Small sample size Did not investigate other causes of CANE | Recall bias, limited generalisability |
| Lin, Bai, Chen et al 1999 | China | Retrospective | Patient interview with psychiatrist. Patients asked for the presence of NEand Ul. Medical and nursing notes reviewed | 61 inpatients from one hospital | Schizophrenia | 61% male | Mean dose 390.2mg | Benzodiazepenes, antidepressants, lithium, anticholinergics, antipsychotics, anticonvulsants | 41% episode prevalence since starting clozapine | CANE may be persistent | Did not explore other causes of CANE | Recall bias Small sample size | |
| Warner, Harvey, Barnes 1994 | United Kingdom | Retrospective | Patient interview. Patients asked for the presence of NE. Medical and nursing notes reviewed | 12 inpatients and outpatients receiving clozapine under one clinical team | Schizophrenia | 67% male | 41.5 | Mean dose 396mg Range 300-750mg | Not specified | 42% episode prevalence since starting clozapine | CANE started within three months of clozapine initiation. CANE is underreported | Did not explore other possible causes of CANE | Recall bias, Small sample size |