Clozapine

Approximately one-third of individuals with a diagnosis of schizophrenia experience persistent symptoms non-responsive to conventional treatment and are described as “treatment resistant”. Repeated relapse can lead to the development of such persistent symptoms that are progressively non-responsive to medication. All evidence based treatment guidelines for schizophrenia contain similar definitions of treatment resistance: the failure to obtain an adequate reduction in target symptoms despite the use of at least two separate trials of antipsychotic monotherapy of adequate dose and duration – at least one of the medication trials should be an atypical antipsychotic agent.

Clozapine is regarded as the gold standard in treatment-resistant cases. Beyond greater effectiveness on symptoms of psychosis, clozapine is associated with lower risk for suicide, fewer hospitalizations and fewer movement disorders than other antipsychotic agents. Regular blood monitoring must be undertaken with clozapine use because of the 1% rate of agranulocytosis.

As soon as treatment resistance is identified, a trial of clozapine should be discussed among the prescribing physician, treatment team, and the client and family.