Publications by authors named "Isabella R Willcocks"

Article Synopsis
  • Clozapine is effective for treatment-resistant schizophrenia but can cause serious side effects like neutropenia and agranulocytosis.
  • A study involving 811 clozapine users found that higher daily doses of the drug lead to increased neutrophil counts, with specific pharmacokinetic and genetic factors influencing this effect.
  • The findings suggest that monitoring these variables could help identify patients at risk for adverse reactions, allowing for tailored preventative measures.
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Background: Treatment-resistant schizophrenia affects approximately 30% of individuals with the disorder. Clozapine is the medication of choice in treatment-resistant schizophrenia, but optimizing administration and dose titration is complex. The identification of factors influencing clozapine prescription and response, including genetics, is of interest in a precision psychiatry framework.

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Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown.

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Up to one-third of those with schizophrenia fail to respond to standard antipsychotics and are considered to have treatment-resistant schizophrenia, a condition for which clozapine is the only evidence-based medication. While up to 60% of treated individuals obtain therapeutic benefits from clozapine, it is currently underprescribed worldwide, partly because of concerns related to its broad adverse effect profile. In particular, the potential effects of clozapine on the immune system have gained relevance after a recent study showed that drug plasma concentrations were inversely correlated with neutrophil counts in individuals routinely undergoing treatment.

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