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Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics

Overview of attention for article published in Pharmacogenomics and Personalized Medicine, November 2016
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Title
Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics
Published in
Pharmacogenomics and Personalized Medicine, November 2016
DOI 10.2147/pgpm.s115741
Pubmed ID
Authors

John Lally, Fiona Gaughran, Philip Timms, Sarah R Curran

Abstract

Up to 30% of people with schizophrenia do not respond to two (or more) trials of dopaminergic antipsychotics. They are said to have treatment-resistant schizophrenia (TRS). Clozapine is still the only effective treatment for TRS, although it is underused in clinical practice. Initial use is delayed, it can be hard for patients to tolerate, and clinicians can be uncertain as to when to use it. What if, at the start of treatment, we could identify those patients likely to respond to clozapine - and those likely to suffer adverse effects? It is likely that clinicians would feel less inhibited about using it, allowing clozapine to be used earlier and more appropriately. Genetic testing holds out the tantalizing possibility of being able to do just this, and hence the vital importance of pharmacogenomic studies. These can potentially identify genetic markers for both tolerance of and vulnerability to clozapine. We aim to summarize progress so far, possible clinical applications, limitations to the evidence, and problems in applying these findings to the management of TRS. Pharmacogenomic studies of clozapine response and tolerability have produced conflicting results. These are due, at least in part, to significant differences in the patient groups studied. The use of clinical pharmacogenomic testing - to personalize clozapine treatment and identify patients at high risk of treatment failure or of adverse events - has moved closer over the last 20 years. However, to develop such testing that could be used clinically will require larger, multicenter, prospective studies.

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Geographical breakdown

Country Count As %
Unknown 344 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 63 18%
Student > Master 42 12%
Researcher 36 10%
Student > Ph. D. Student 31 9%
Student > Postgraduate 27 8%
Other 56 16%
Unknown 89 26%
Readers by discipline Count As %
Medicine and Dentistry 81 24%
Neuroscience 34 10%
Pharmacology, Toxicology and Pharmaceutical Science 27 8%
Biochemistry, Genetics and Molecular Biology 21 6%
Psychology 21 6%
Other 55 16%
Unknown 105 31%