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Br J Psychiatry. 2015 Jun;206(6):484-91. doi: 10.1192/bjp.bp.114.151837. Epub 2015 Mar 5.

Response to clozapine in a clinically identifiable subtype of schizophrenia.

Author information

1
Nancy J. Butcher, MSc, Clinical Genetics Research Program, Centre for Addiction and Mental Health and Institute of Medical Science, University of Toronto, Toronto; Wai Lun Alan Fung, MD, ScD, FRCPC, Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto General Research Institute, University Health Network, Toronto, The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome and Department of Psychiatry, University Health Network and Department of Psychiatry, University of Toronto, Toronto; Laura Fitzpatrick, Alina Guna, BSc, Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto; Danielle M. Andrade, MD, MSc, FRCPC, Division of Neurology, Department of Medicine, University of Toronto, Toronto; Anthony E. Lang, MD, FRCPC, Institute of Medical Science, University of Toronto, Division of Neurology, Department of Medicine, University of Toronto, Tanz Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, Toronto Western Hospital Research Institute, University Health Network and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto; Eva W. C. Chow, MD, MPH, FRCPC, Clinical Genetics Research Program, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto; Anne S. Bassett, MD, FRCPC, Clinical Genetics Research Program, Centre for Addiction and Mental Health, Institute of Medical Science, University of Toronto, Toronto General Research Institute, University Health Network, The Dalglish Family Hearts and Minds Clinic for Adults with 22q11.2 Deletion Syndrome, Department of Medicine and Department of Psychiatry, University Health Network, Department of Psychiatry, University of Toronto, Ontario, Canada.

Abstract

BACKGROUND:

Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples.

AIMS:

To determine whether patients with a well-established genetic subtype of schizophrenia show a different response profile to the antipsychotic clozapine than those with idiopathic schizophrenia.

METHOD:

We retrospectively studied the long-term safety and efficacy of clozapine in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS group) and half matched for age and clinical severity but molecularly confirmed to have no pathogenic copy number variant (idiopathic group).

RESULTS:

Both groups showed similar clinical improvement and significant reductions in hospitalisations, achieved at a lower median dose for those in the 22q11.2DS group. Most common side-effects were similarly prevalent between the two groups, however, half of the 22q11.2DS group experienced at least one rare serious adverse event compared with none of the idiopathic group. Many were successfully retried on clozapine.

CONCLUSIONS:

Individuals with 22q11.2DS-schizophrenia respond as well to clozapine treatment as those with other forms of schizophrenia, but may represent a disproportionate number of those with serious adverse events, primarily seizures. Lower doses and prophylactic (for example anticonvulsant) management strategies can help ameliorate side-effect risks. This first systematic evaluation of antipsychotic response in a genetic subtype of schizophrenia provides a proof-of-principle for personalised medicine and supports the utility of clinical genetic testing in schizophrenia.

PMID:
25745132
PMCID:
PMC4459828
DOI:
10.1192/bjp.bp.114.151837
[Indexed for MEDLINE]
Free PMC Article

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