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