Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review

Tanzer, Timothy; Warren, Nicola; McMahon, Laura; Barras, Michael; Kisely, Steve; Brooks, Emily; Wong, Emily; Siskind, Dan

doi:10.1017/s1092852922000050

Cited by 9 publications

(9 citation statements)

References 70 publications

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“…Several countries require enrolment in clozapine patient-monitoring registries. Other side effects like nocturnal enuresis or incontinence can be troubling to the patient, and have major consequences if their burden leads to nonadherence and psychotic relapse [ 108 ].…”

Section: Side Effect Monitoring and Managementmentioning

confidence: 99%

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

et al. 2022

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Section: Side Effect Monitoring and Managementmentioning

confidence: 99%

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

et al. 2022

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“… 91 In addition, clozapine’s antagonistic properties at adrenergic receptors have been linked to nocturnal enuresis, hypotension, and hypersalivation. 92 , 93 …”

Section: Pharmacodynamicsmentioning

confidence: 99%

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Qubad

Bittner

2023

Therapeutic Advances in Psychopharmacology

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Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.

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“…Other clinically relevant side effects: hepatitis, nephritis, pancreatitis 419,420 , delirium*, enuresis, NMS 90,91,146,298,421,422 , DRESS syndrome 392,423 , venous thromboembolism 148,162 , diabetic ketoacidosis, hyperosmolar coma 148,251  Clinical assessment, laboratory parameter 424  Cave: delirium associated with high clozapine doses and with abrupt clozapine discontinuation 274,424  NMS: rare (clozapine drug of first choice after NMS) 298,422,425  Pancreatitis: screen for signs of exocrine and endocrine pancreas insufficiency  DRESS syndrome: assess laboratory parameter frequently (especially eosinophils, lymphocytes) 392,423 ; risk factor: combination with lithium, anticonvulsants (incl. valproate)…”

Section: Fridericia) 137mentioning

confidence: 99%

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

Qubad¹,

Bittner²

2022

Preprint

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Despite its continued relevance as the single most effective and important evidence-based treatment for schizophrenia, the degree of underutilization of clozapine across health systems remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to use clozapine due to its relatively large side-effect burden and its comparatively complex dosing and monitoring requirements. This underscores the necessity for continued education of clinicians in the intricacies of clozapine use and in the still growing case in favor of this vital treatment option. Consequently, this narrative review provides a comprehensive outline of all lines of evidence, which support clozapine’s wide-ranging superior efficacy, and of the current knowledge regarding the prevalence and diagnosis of treatment resistance. The distinct neurobiological and clinical characteristics of this condition makes the swift initiation of clozapine indispensable. Moreover, we review the extensive literature regarding clozapine’s side effect profile and current recommendations for optimal treatment and monitoring algorithms including for particularly vulnerable populations such as elderly patients and pregnant women and for potential re-challenges after myocarditis and neutropenia. We also discuss established approaches to increase treatment response as well as augmentation strategies for patients with partial or full clozapine resistance. We argue for a clear focus on early and consistent detection and management of side effects, which can ensure patient safety and reduce permanent all-cause discontinuation. This strategy needs to be combined with a long-term approach acknowledging the late onset of clozapine’s full advantageous effects, which – in cases like reduced mortality rates – even then may not be easily discernible. Our aim is to encourage a safer, more frequent, and timely use of clozapine to maximize patients’ short- and long-term benefits. Even now, the extent of these benefits as well as patient’s satisfaction with treatment still clearly set clozapine apart from all other available treatment options.

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Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review

Cited by 9 publications

References 70 publications

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Second to None – Rationale, Timing, and Clinical Management of Clozapine Use in Schizophrenia

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