Response to clozapine in a clinically identifiable subtype ofschizophrenia

BackgroundGenetic testing in psychiatry promises to improve patient care throughadvances in personalised medicine. However, there are few clinicallyrelevant examples.AimsTo determine whether patients with a well-established genetic subtype ofschizophrenia show a different response profile to the antipsychoticclozapine than those with idiopathic schizophrenia.MethodWe retrospectively studied the long-term safety and efficacy of clozapinein 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DSgroup) and half matched for age and clinical severity but molecularlyconfirmed to have no pathogenic copy number variant (idiopathicgroup).ResultsBoth groups showed similar clinical improvement and significantreductions in hospitalisations, achieved at a lower median dose for thosein the 22q11.2DS group. Most common side-effects were similarly prevalentbetween the two groups, however, half of the 22q11.2DS group experiencedat least one rare serious adverse event compared with none of theidiopathic group. Many were successfully retried on clozapine.ConclusionsIndividuals with 22q11.2DS-schizophrenia respond as well to clozapinetreatment as those with other forms of schizophrenia, but may represent adisproportionate number of those with serious adverse events, primarilyseizures. Lower doses and prophylactic (for example anticonvulsant)management strategies can help ameliorate side-effect risks. This firstsystematic evaluation of antipsychotic response in a genetic subtype ofschizophrenia provides a proof-of-principle for personalised medicine andsupports the utility of clinical genetic testing in schizophrenia.