In the study, patients were treated for 4 weeks with up to 800 mg/day amisulpride orally in an open-label design (phase 1). Patients who did not meet symptomatic remission criteria at 4 weeks were randomly assigned to continue amisulpride or switch to olanzapine (≤20 mg/day) during a 6-week double-blind phase (phase 2). Patients who were not in remission at 10 weeks were given clozapine (≤900 mg/day) for an additional 12 weeks (phase 3).
According to a commentary, given the substantial risks associated with clozapine, including agranulocytosis, myocarditis, intestinal obstruction, and severe weight gain, confidence that antipsychotics with fewer risks would not be effective is necessary before a trial of clozapine should be recommended. It suggests that in clinical practice, it would be valuable to know whether treatment with a long-acting injectable antipsychotic should be offered to patients with first-episode schizophrenia before recommending clozapine, given the evidence that poor treatment response might result from non-adherence. It adds that given recent evidence that second-generation, long-acting injectable antipsychotics might substantially reduce the proportion who relapse in this patient group, and might also be associated with reduced mortality, it would be of particular interest to know how many patients benefit from these medications before being offered a trial of clozapine.