Response to clozapine in a clinically identifiable subtype of schizophrenia
Identifieur interne : 000549 ( Main/Exploration ); précédent : 000548; suivant : 000550Response to clozapine in a clinically identifiable subtype of schizophrenia
Auteurs : Nancy J. Butcher ; Wai Lun Alan Fung ; Laura Fitzpatrick ; Alina Guna ; Danielle M. Andrade ; Anthony E. Lang ; Eva W. C. Chow ; Anne S. BassettSource :
- The British journal of psychiatry : the journal of mental science [ 0007-1250 ] ; 2015.
Abstract
Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples.
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.
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).
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.
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.
Url:
DOI: 10.1192/bjp.bp.114.151837
PubMed: 25745132
PubMed Central: 4459828
Affiliations:
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Genetic testing in psychiatry promises to improve patient care through advances in personalised medicine. However, there are few clinically relevant examples.</p>
</sec>
<sec id="S2"><title>Aims</title>
<p id="P2">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.</p>
</sec>
<sec id="S3"><title>Method</title>
<p id="P3">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).</p>
</sec>
<sec id="S4"><title>Results</title>
<p id="P4">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.</p>
</sec>
<sec id="S5"><title>Conclusions</title>
<p id="P5">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.</p>
</sec>
</div>
</front>
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<name sortKey="Butcher, Nancy J" sort="Butcher, Nancy J" uniqKey="Butcher N" first="Nancy J." last="Butcher">Nancy J. Butcher</name>
<name sortKey="Chow, Eva W C" sort="Chow, Eva W C" uniqKey="Chow E" first="Eva W. C." last="Chow">Eva W. C. Chow</name>
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<name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name>
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