A patient with psychotic symptoms; first-line antipsychotic choice?

• A. First-generation antipsychotic (e.g., haloperidol) alone.
• B. Atypical antipsychotic monotherapy without psychosocial support.
• C. Second-generation antipsychotic (e.g., risperidone) with psychosocial support.
• D. Clozapine monotherapy.

Answer: (D)

Clozapine stands out when psychotic symptoms are treatment-resistant or when suicidality is a major concern. It has unique efficacy in patients who have not adequately responded to other antipsychotics and it, unlike other agents, is proven to reduce the risk of suicide in schizophrenia. Because of this, in a scenario where a patient’s psychosis is difficult to control with standard therapies or where there is a high suicide risk, starting or continuing clozapine can lead to significantly better outcomes. Of course, it requires careful monitoring due to the risk of agranulocytosis and other adverse effects, with regular blood counts (weekly initially, then less frequently if stable). This balancing of superior effectiveness in refractory illness against the need for strict safety monitoring is why clozapine monotherapy is the best choice in this context.