Response to clozapine in a clinically identifiable subtype of schizophrenia - PubMed (original) (raw)

Observational Study

Response to clozapine in a clinically identifiable subtype of schizophrenia

Nancy J Butcher et al. Br J Psychiatry. 2015 Jun.

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.

© The Royal College of Psychiatrists 2015.

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Conflict of interest statement

Declaration of interest None.

Figures

Fig. 1

Fig. 1. Patients with 22q11.2 deletion syndrome (22q11.2DS) schizophrenia are maintained on a significantly lower therapeutic dose of clozapine than patients with idiopathic schizophrenia (P = 0.002)

The two 22q11.2DS-schizophrenia patients with doses ≤150 mg had been maintained in this range for at least 1 year; one was receiving adjunct antipsychotic flupentixol (4.5 mg) treatment. Of the three patients in the idiopathic group on a clozapine dose ≤150 mg, one was maintained on this dose for 4 years; the other two discontinued within 9 and 28 weeks, respectively (the latter on adjunct antipsychotic perphenazine (48 mg) treatment) and were not titrated above this low dose range.

Fig. 2

Fig. 2. Clinical Global Impression – Improvement scale ratings for patients with 22q11.2 deletion syndrome (22q11.2DS) schizophrenia and idiopathic schizophrenia

Therapeutic response to clozapine of patients in the 22q11.2DS group is similar to those in the idiopathic group (P = 0.33). One of the two patients with no change corresponds to a patient in the idiopathic group with a clozapine dose ≤150 mg who discontinued within 28 weeks of treatment.

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