{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:23:01Z","timestamp":1791260581030,"version":"4.1.0"},"reference-count":159,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine, University of Alberta, Edmonton, AB, Canada","award":["TRP-GB"],"award-info":[{"award-number":["TRP-GB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Clozapine is superior to other antipsychotics as a therapy for treatment-resistant schizophrenia and schizoaffective disorder with increased risk of suicidal behavior. This drug has also been used in the off-label treatment of bipolar disorder, major depressive disorder (MDD), and Parkinson\u2019s disease (PD). Although usually reserved for severe and treatment-refractory cases, it is interesting that electroconvulsive therapy (ECT) has also been used in the treatment of these psychiatric disorders, suggesting some common or related mechanisms. A literature review on the applications of clozapine and electroconvulsive therapy (ECT) to the disorders mentioned above was undertaken, and this narrative review was prepared. Although both treatments have multiple actions, evidence to date suggests that the ability to elicit epileptiform activity and alter EEG activity, to increase neuroplasticity and elevate brain levels of neurotrophic factors, to affect imbalances in the relationship between glutamate and \u03b3-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron\u2013glia interactions are common underlying mechanisms of these two treatments. This evidence may explain why clozapine is effective in a range of neuropsychiatric disorders. Future increased investigations into epigenetic and connectomic changes produced by clozapine and ECT should provide valuable information about these two treatments and the disorders they are used to treat.<\/jats:p>","DOI":"10.3390\/biom11071030","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T02:52:34Z","timestamp":1626317554000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?"],"prefix":"10.3390","volume":"11","author":[{"given":"Dara","family":"Gammon","sequence":"first","affiliation":[{"name":"Saba University School of Medicine, Saba, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Cheng","sequence":"additional","affiliation":[{"name":"Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Volkovinskaia","sequence":"additional","affiliation":[{"name":"Saba University School of Medicine, Saba, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen B.","family":"Baker","sequence":"additional","affiliation":[{"name":"Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada"},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-851X","authenticated-orcid":false,"given":"Serdar M.","family":"Dursun","sequence":"additional","affiliation":[{"name":"Neurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada"},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"ref_1","first-page":"22","article-title":"A historical perspective of clozapine","volume":"60","author":"Hippius","year":"1999","journal-title":"J. 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