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Related Concept Videos

Psychological and Sociocultural Causes of Schizophrenia01:29

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Schizophrenia, a complex psychiatric disorder, has been historically misunderstood. Early psychological theories attributed its origins to childhood trauma and unresponsive parenting. However, contemporary research largely rejects these notions, favoring the vulnerability-stress hypothesis. This model proposes that individuals with a genetic predisposition to schizophrenia may develop the disorder following exposure to significant environmental stressors. Notably, studies on high-risk...
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Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation.
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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
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Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
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Truncation in survival analysis refers to the exclusion of individuals or events from the dataset based on specific criteria related to the time of the event. This exclusion can happen in two primary forms: left truncation and right truncation.
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Risk factors for early-phase clozapine discontinuation: A nested case-control study.

Mariko Tsukiji1, Tsuyoshi Sasaki2, Yusuke Nakata3

  • 1Division of Pharmacy, Chiba University Hospital, Chiba, Japan.

Asian Journal of Psychiatry
|July 3, 2021
PubMed
Summary

Clozapine is effective for treatment-resistant schizophrenia (TRS) in Japan. Early clozapine discontinuation is linked to smoking history and lower prior antipsychotic doses, with valproate increasing eosinophilia risk.

Keywords:
AntipsychoticClozapineEosinophiliaSwitching strategyTreatment-resistant schizophreniaValproate

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Area of Science:

  • Psychiatry
  • Pharmacology
  • Clinical Medicine

Background:

  • Treatment-resistant schizophrenia (TRS) requires safe and effective therapeutic options.
  • Clozapine is a critical medication for managing TRS, but its introduction can be challenging.
  • Understanding early discontinuation risks is vital for optimizing clozapine therapy.

Purpose of the Study:

  • To identify risk factors associated with early clozapine discontinuation in patients with TRS.
  • To evaluate the safety and efficacy of clozapine introduction in a Japanese cohort.

Main Methods:

  • A nested case-control study was conducted across 14 psychiatric hospitals in Japan.
  • Data from 228 TRS patients were collected up to 12 weeks pre- and post-clozapine initiation.
  • Risk factors analyzed included demographics, prior/concomitant medications, and clinical assessments.

Main Results:

  • Clozapine was continued in 93.4% of patients within 12 weeks, with 14.9% showing symptom improvement.
  • Smoking history and prior antipsychotic treatment <1200 mg chlorpromazine equivalents increased discontinuation risk.
  • Eosinophilia, linked to concomitant valproate, was the primary discontinuation reason (20%).

Conclusions:

  • Clozapine is effective for TRS patients in Japan, particularly those previously on higher antipsychotic doses.
  • Clinicians must monitor for eosinophilia when initiating clozapine with valproate.
  • Early identification of risk factors can improve clozapine treatment outcomes.