Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?

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’s diseas...

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Main Authors: Dara Gammon, Catherine Cheng, Anna Volkovinskaia, Glen B. Baker, Serdar M. Dursun
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/7/1030
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author Dara Gammon
Catherine Cheng
Anna Volkovinskaia
Glen B. Baker
Serdar M. Dursun
author_facet Dara Gammon
Catherine Cheng
Anna Volkovinskaia
Glen B. Baker
Serdar M. Dursun
author_sort Dara Gammon
collection DOAJ
description 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’s 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 γ-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron–glia 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.
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spelling doaj.art-fdfef2c6e3824356b59b111b9d9faea72023-11-22T03:19:05ZengMDPI AGBiomolecules2218-273X2021-07-01117103010.3390/biom11071030Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?Dara Gammon0Catherine Cheng1Anna Volkovinskaia2Glen B. Baker3Serdar M. Dursun4Saba University School of Medicine, Saba, The NetherlandsNeurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, CanadaSaba University School of Medicine, Saba, The NetherlandsNeurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, CanadaNeurochemical Research Unit and Bebensee Schizophrenia Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, CanadaClozapine 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’s 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 γ-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron–glia 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.https://www.mdpi.com/2218-273X/11/7/1030clozapineantipsychoticselectroconvulsive therapyschizophreniasuicidebipolar disorder
spellingShingle Dara Gammon
Catherine Cheng
Anna Volkovinskaia
Glen B. Baker
Serdar M. Dursun
Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
Biomolecules
clozapine
antipsychotics
electroconvulsive therapy
schizophrenia
suicide
bipolar disorder
title Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
title_full Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
title_fullStr Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
title_full_unstemmed Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
title_short Clozapine: Why Is It So Uniquely Effective in the Treatment of a Range of Neuropsychiatric Disorders?
title_sort clozapine why is it so uniquely effective in the treatment of a range of neuropsychiatric disorders
topic clozapine
antipsychotics
electroconvulsive therapy
schizophrenia
suicide
bipolar disorder
url https://www.mdpi.com/2218-273X/11/7/1030
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