&lt;p&gt;Clozapine As Transformative Treatment In Bipolar Patients&lt;/p&gt;

Wilkowska, Aleksandra; Cubała, Wiesław Jerzy

doi:10.2147/ndt.s227196

Cited by 17 publications

(15 citation statements)

References 50 publications

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“…However, in a recent review of literature, clozapine was shown as an effective and safe treatment in resistant BD, with lower severe adverse effects reported than those reported in the published schizophrenia literature, with just 0.3% of agranulocytosis (61). Therefore, and considering its unique properties (including its antisuicidal effects and by extrapolation from its likely superiority in treating psychosis (62)), it is becoming more used and seen by many as a useful treatment in resistant BD (63, 64).…”

Section: Resultsmentioning

confidence: 99%

How to treat mania

Pacchiarotti

Anmella

Colomer

et al. 2020

Acta Psychiatr Scand

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Objective In this paper, we aimed at reviewing evidence‐based treatment options for bipolar mania and proposed tentative evidence‐based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication. Method A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices. Results To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment‐refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long‐term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence. Discussion Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long‐term.

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Section: Resultsmentioning

confidence: 99%

How to treat mania

Pacchiarotti

Anmella

Colomer

et al. 2020

Acta Psychiatr Scand

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“…Early-onset schizophrenia occurs before age 18; very early-onset schizophrenia (EOS) or childhood-onset schizophrenia (COS) begins at under 13 years old and is extremely rare [ 118 ]. It is well known that EOS has a poorer prognosis and more severe symptoms, as it affects the individual before the brain and personality are fully developed.…”

Section: Resultsmentioning

confidence: 99%

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

et al. 2020

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Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

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“…Overall, CLZ has been utilized as an antipsychotic drug due to its simultaneous affinity for both dopamine and serotonin receptors [ 28 ]. Nonetheless, its complex mechanisms of action are not yet fully known, involving the modulation of norepinephrine, the regulation of the endocrine system (including pregnenolone and cortisol), the intracellular system-dependent modulation of N -methyl- d -aspartate (NMDA) receptor expression, brain-derived neurotrophic factor up-regulation, and the regulation of the arachidonic acid cascade [ 29 , 30 , 31 , 32 ]. Herein, we performed an integration of the genomic and epigenomic data of CLZ-associated phenotypes to identify genes related to the potential mechanisms of action of CLZ and possible pharmacogenomic applications.…”

Section: Discussionmentioning

confidence: 99%

Integrative Genomic–Epigenomic Analysis of Clozapine-Treated Patients with Refractory Psychosis

et al. 2021

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Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to be enriched in BD-PRS and was associated with the CLZ metabolic ratio. Such interplay supports the use of CLZ as a mood stabilizer and not just as an antipsychotic. Future studies with larger sample sizes should be pursued to confirm the findings of this study.

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<p>Clozapine As Transformative Treatment In Bipolar Patients</p>

Cited by 17 publications

References 50 publications

How to treat mania

How to treat mania

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

Integrative Genomic–Epigenomic Analysis of Clozapine-Treated Patients with Refractory Psychosis

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