{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:59:43Z","timestamp":1792144783219,"version":"4.4.0"},"reference-count":76,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Spectr."],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S1092852922000050_sec1\"><jats:title>Background<\/jats:title><jats:p>Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852922000050_sec2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852922000050_sec3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.<\/jats:p><\/jats:sec><jats:sec id=\"S1092852922000050_sec4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s1092852922000050","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T08:53:31Z","timestamp":1643360011000},"page":"133-144","source":"Crossref","is-referenced-by-count":15,"title":["Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review"],"prefix":"10.1017","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-3320","authenticated-orcid":false,"given":"Timothy","family":"Tanzer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Warren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"McMahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Barras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Kisely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Siskind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"S1092852922000050_r64","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00612-8"},{"key":"S1092852922000050_r57","doi-asserted-by":"publisher","DOI":"10.1177\/1756287213502116"},{"key":"S1092852922000050_r12","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.110.087478"},{"key":"S1092852922000050_r35","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000001283"},{"key":"S1092852922000050_r59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002930"},{"key":"S1092852922000050_r40","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.19l02530"},{"key":"S1092852922000050_r48","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05746-y"},{"key":"S1092852922000050_r55","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2015.11.006"},{"key":"S1092852922000050_r75","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.17l02161"},{"key":"S1092852922000050_r17","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.149.2.224"},{"key":"S1092852922000050_r3","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby052"},{"key":"S1092852922000050_r46","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.6.975"},{"key":"S1092852922000050_r69","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198938010-00003"},{"key":"S1092852922000050_r7","doi-asserted-by":"publisher","DOI":"10.2478\/gp-2018-0007"},{"key":"S1092852922000050_r16","doi-asserted-by":"publisher","DOI":"10.1097\/00004714-198410000-00003"},{"key":"S1092852922000050_r22","doi-asserted-by":"publisher","DOI":"10.1177\/0004867415583878"},{"key":"S1092852922000050_r1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.115.177261"},{"key":"S1092852922000050_r50","doi-asserted-by":"publisher","DOI":"10.1177\/0004867418772351"},{"key":"S1092852922000050_r4","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12898"},{"key":"S1092852922000050_r32","doi-asserted-by":"publisher","DOI":"10.1016\/0924-9338(96)80348-8"},{"key":"S1092852922000050_r36","first-page":"280","article-title":"Clozapine induced urinary incontinence during sleep","volume":"46","author":"Bhirud","year":"2004","journal-title":"Indian J Psychiatry."},{"key":"S1092852922000050_r14","doi-asserted-by":"publisher","DOI":"10.1192\/pb.25.6.232"},{"key":"S1092852922000050_r31","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2010.25.2.333"},{"key":"S1092852922000050_r25","first-page":"234","article-title":"Clozapine induced enuresis treated with amitriptyline: a case report","volume":"8","author":"Demirkol","year":"2017","journal-title":"J Clin Anal Med."},{"key":"S1092852922000050_r63","doi-asserted-by":"publisher","DOI":"10.1592\/phco.19.4.267.30943"},{"key":"S1092852922000050_r54","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e31819cc8e6"},{"key":"S1092852922000050_r60","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.03.095"},{"key":"S1092852922000050_r19","unstructured":"19. 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