Should You Start Clozapine After Only One Failed Antipsychotic?

<jats:p>In this first-episode psychosis trial, clozapine outperformed olanzapine and amisulpride in patients who failed one antipsychotic. Most treatment-resistant schizophrenia is present from the first episode, so a second dopamine blocker may add little after one clear failure. There are still reasons to try a second antipsychotic first, including a long-acting injectable for partial adherence or replacing a poorly tolerated agent. Focus on time lost to ineffective treatment, not the number of antipsychotics tried; consider clozapine early, after three to four months of inadequate response.</jats:p>