Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement

Kar, Nilamadhab; Barreto, Socorro; Chandavarkar, Rahul

doi:10.9758/cpn.2016.14.4.323

Cited by 62 publications

(41 citation statements)

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“…Early detection of cardiac abnormalities is not only crucial for preventing fatalities, but will also reduce the eventual costs of health care in the long run. Every effort should be made in maximizing the therapeutic benefits of CLZ, which remains heavily underutilized in managing treatment-resistant schizophrenia (Kar et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Any therapeutic benefit from CLZ treatment, however, must take into consideration the high incidence of non-EPS side-effects associated with the drug (Andreazza et al, 2015 ; Thornton et al, 2015 ; Tse et al, 2015 ; Lee et al, 2016 ). An estimated 10–20% of eligible patients are prescribed with CLZ in the U.S., a number indicative that CLZ is vastly underutilized due to concern for its side effects (Meltzer, 2012 ; Kar et al, 2016 ). One of the most concerning side effects of CLZ is agranulocytosis, which occurs in approximately 1% of patients receiving CLZ (Alvir et al, 1993 ) and only rarely with other antipsychotics (Vila-Rodriguez et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

et al. 2018

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Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these.Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment.Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline.Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports.Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

et al. 2018

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“…Assim, observa-se que o diagnóstico menos preciso de um e de outro transtorno pode levar o curso da patologia a resultados bem distintos, conforme o tratamento adotado: na esquizofrenia, ele inclui a farmacologia, com a prescrição de antipsicóticos que inibem muito os receptores da dopamina das vias dopaminérgicas; neurolépticos, indicados para pacientes que não respondem aos antipsicóticos convencionais ou que sofrem efeitos colaterais indesejáveis. Também há indicação de psicoterapia, com a finalidade, entre outras, de interromper a perda da capacidade mental, preservando o contato com a realidade (Amato, Beasley, Hahn, & Vernon, 2016;Kar, Barreto, & Chandavarkar, 2016;Maramai et al, 2016).…”

Section: Discussionunclassified

A utilização do Método de Rorschach no diagnóstico diferencial da Esquizofrenia e Transtorno Dissociativo de Identidade

Faria

Prado

Souza

et al. 2019

Psic.: Teor. e Pesq.

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RESUMO -o objetivo deste artigo foi investigar a prevalência do Transtorno Dissociativo de Identidade (TDI) em dez pacientes diagnosticados com esquizofrenia com característica paranóide, com base no Método de Rorschach. Foram registrados indicadores ou sintomas psicológicos que caracterizaram o diagnóstico diferencial desses pacientes, analisadas diferenças clínicas específicas e verificado o enquadramento dos dados obtidos, com a aplicação da Técnica de Rorschach. Para fins de diagnóstico diferencial, observou-se que dois pacientes apresentaram sintomas diferenciais aos da esquizofrenia, sendo que um deles apresentou sintomas dissociativos, não sendo confirmada a prevalência do TDI entre os esquizofrênicos. No caso da esquizofrenia e do TDI, devido às características similares que apresentam, avaliações multidisciplinares são indicadas para se fazer o diagnóstico diferencial entre eles. PALAVRAS-CHAVE: esquizofrenia, transtorno dissociativo de identidade, trauma, rorschach ABSTRACT -The aim of this article was to investigate the prevalence of the Dissociative Identity Disorder (DID) in ten patients diagnosed with schizophrenia with paranoid characteristic, based on the Rorschach approach. Psychological symptoms that characterize the differential diagnosis of these patients were registered, specific clinical differences were analyzed and the framework of the data obtained with the application of the Rorschach approach. For purposes of differential diagnosis, it was observed that two patients had differential symptoms to schizophrenia, one of which showed dissociative symptoms, not confirmed the prevalence of DID among schizophrenics. In the case of schizophrenia and DID due to exhibit similar characteristics, multidisciplinary evaluations are set to make a differential diagnosis between them.

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“…Currently, clozapine (CLZ) is considered the most effective antipsychotic medication for schizophrenia and it is the only one whose efficacy can be predicted by a blood test . In addition, CLZ is the only antipsychotic drug currently approved for treatment‐resistant schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

“…However, this method, which measures total CLZ in blood, is unable to distinguish between the therapeutically inactive protein‐bound and the active unbound CLZ; furthermore, it requires more specialized staff and needs to be performed in commercial laboratories . Moreover, since frequent blood draws are required (at least once a week at the beginning of the treatment), to provide sufficient information about the CLZ kinetics and to devise an appropriate treatment scheme, the burden on patients is enormous. Furthermore, in cases of patients with acute psychosis, physicians require a rapid estimation (several minutes only) of CLZ blood levels to accurately adjust the administered CLZ dose, a requirement that the current gold standard tests cannot provide.…”

Section: Introductionmentioning

confidence: 99%

A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume

Shukla

Ben‐Yoav

2019

Adv Healthcare Materials

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addition, CLZ is the only antipsychotic drug currently approved for treatmentresistant schizophrenia. The FDA has recently permitted greater flexibility in deciding whether to continue or rechallenge CLZ in patients. [2] However, CLZ, although a common evidence-based treatment in the field of mental health, is underutilized. The monitoring of CLZ is burdensome and involves frequent invasive blood draws and its treatment efficacy is suboptimal due to the difficulty in titrating its dose, since over dosage results in toxicity as well as possible side effects such as weight gain, blurred vision, confusion, fever, sweating, and dizziness. [3][4][5] Since CLZ is the only antipsychotic with a defined efficacious clinical range, [6,7] analyzing CLZ blood levels in patients easily and accurately provides important information about the clinical range. For example, CLZ serum levels that are higher than 600 ng mL −1 (1.84 µmol L −1 ) have been associated with severe side effects, toxicity, seizure, and myocarditis. [8][9][10][11][12][13][14] However, psychiatrists estimate that CLZ blood levels should be higher than a 350 ng mL −1 (1.07 µmol L −1 ) threshold level to achieve effective treatment. [15,16] Therefore, clinicians have been advocating therapeutic drug monitoring (TDM) for CLZ therapy [9,17] that can be rapidly done at the point-of-care (PoC), such as at the physician's office or at home. Along the lines of the medical treatment revolution that the glucose finger-prick blood test provided for diabetes patients, in situ analysis of CLZ blood levels in microliter samples would enable rapid CLZ detection in finger-pricked blood of schizophrenia patients. Such a blood test would provide rapid assessment of CLZ treatment efficacy, which would better manage schizophrenia treatment and care.Current analytical methods for TDM of CLZ blood levels have limited capabilities to rapidly measure CLZ levels in microliter samples. [18][19][20][21][22][23][24][25][26] Liquid chromatography, followed by tandem mass spectrometry (LC-MS/MS), [23] is the gold standard and is available in commercial laboratories. A variation of the method used for venous blood has been adapted to low-volume capillary blood using dried blood spot testing. [24,25] Briefly, the sample is dehydrated on filter paper, transferred to an analytical laboratory, and rehydrated for further analysis using an LC-MS/MS. Although the LC-MS/MS method provides The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger-pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer-thick biop...

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Clozapine Monitoring in Clinical Practice: Beyond the Mandatory Requirement

Cited by 62 publications

References 58 publications

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

Clozapine-Induced Cardiovascular Side Effects and Autonomic Dysfunction: A Systematic Review

A utilização do Método de Rorschach no diagnóstico diferencial da Esquizofrenia e Transtorno Dissociativo de Identidade

A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume

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