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

Gammon, Dara; Cheng, Catherine; Volkovinskaia, Anna; Baker, Glen B.; Dursun, Serdar

doi:10.3390/biom11071030

Cited by 41 publications

(32 citation statements)

References 151 publications

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“…Some patients with BD, including those who respond poorly to mood stabilizers and typical antipsychotic agents or who exhibit rapid cycling, may benefit from the use of clozapine [314,322]. Especially among older adults, clozapine may be beneficial in the treatment of BD and psychotic disorders [323].…”

Section: Clozapinementioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

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Section: Clozapinementioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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“…Clozapine affects multiple glutamate/GABA signal transduction receptors, transporters, and enzymes, drawing attention to the interaction between SNP gene variations and clozapine sensitivity in these pathways ( Daskalakis and George, 2009 ; Gammon et al, 2021 ). However, there are no ideal positive results on the relationship between the variation of genes in this system and clozapine response.…”

Section: Peripheral Biomarkers Of Trs With Clozapine Treatmentmentioning

confidence: 99%

Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives

2022

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Treatment-resistant schizophrenia (TRS) often results in severe disability and functional impairment. Currently, the diagnosis of TRS is largely exclusionary and emphasizes the improvement of symptoms that may not be detected early and treated according to TRS guideline. As the gold standard, clozapine is the most prescribed selection for TRS. Therefore, how to predict TRS in advance is critical for forming subsequent treatment strategy especially clozapine is used during the early stage of TRS. Although mounting studies have identified certain clinical factors and neuroimaging characteristics associated with treatment response in schizophrenia, the predictors for TRS remain to be explored. Biomarkers, particularly for peripheral biomarkers, show great potential in predicting TRS in view of their predictive validity, noninvasiveness, ease of testing and low cost that would enable their widespread use. Recent evidence supports that the pathogenesis of TRS may be involved in abnormal neurotransmitter systems, inflammation and stress. Due to the heterogeneity of TRS and the lack of consensus in diagnostic criteria, it is difficult to compare extensive results among different studies. Based on the reported neurobiological mechanisms that may be associated with TRS, this paper narratively reviews the updates of peripheral biomarkers of TRS, from genetic and other related perspectives. Although current evidence regarding biomarkers in TRS remains fragmentary, when taken together, it can help to better understand the neurobiological interface of clinical phenotypes and psychiatric symptoms, which will enable individualized prediction and therapy for TRS in the long run.

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“…Other neurological conditions for which clozapine has been reported to be helpful include refractory rest tremor in Parkinson’s disease (PD), 5,9–13 levodopa ( l -DOPA)–induced dyskinesias (LIDs) in PD, 14,15 tardive movement disorders, 16–20 and dystonia 21,22 and also for the treatment of primary psychotic symptoms in patients who require but fail to tolerate other antipsychotics because of parkinsonism or other movement disorders, including tardive syndromes 2,23 . This includes people with schizophrenia, 24 bipolar disorder, 25 schizoaffective disorder, and other primary psychotic disorders who develop idiopathic PD 26 …”

Section: Ethical Compliance Statementmentioning

confidence: 99%

Clozapine Use in a Movement Disorder Clinic

Friedman

Hershkowitz

2022

Clin Neuropharm

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BackgroundClozapine is an effective antipsychotic for Parkinson’s disease (PD) that does not worsen motor function and can improve tremor. It is approved for PD psychosis in Europe and Australia.ObjectiveThe aim of this study was to report on the use of clozapine in a movement disorder clinic.MethodsWe report on patients monitored during the COVID-19 pandemic in clinic over a 7-month period.ResultsSixty-five patients were seen, of whom 50 had PD. Thirty-one were treated for psychosis, 18 for refractory tremor and 1 for levodopa dyskinesias. The remainder had psychotic symptoms with dementia with Lewy bodies (n = 2) or other movement disorders. Four had clozapine discontinued because of sedation and 1 for agranulocytosis. Three had clozapine temporarily halted because of granulocytopenia but were rechallenged successfully.ConclusionsWhen comparing clozapine use in this clinic as compared with others, we deduce that clozapine is likely significantly underutilized in the United States.

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

Cited by 41 publications

References 151 publications

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives

Clozapine Use in a Movement Disorder Clinic

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