Which two drugs are most commonly associated with aplastic anemia?

• A. Chlorpromazine and trifluoperazine
• B. Clozapine and olanzapine
• C. Haloperidol and risperidone
• D. Quetiapine and ziprasidone

Answer: (A)

Aplastic anemia is a rare but serious condition where the bone marrow fails to produce enough red cells, white cells, and platelets. Among antipsychotics, older phenothiazines have the strongest historical signal for this specific bone marrow suppression. Chlorpromazine and trifluoperazine are the drugs most commonly associated with aplastic anemia because there are notable case reports and pharmacovigilance data linking them to this pancytopenic outcome. The exact mechanism isn’t fully understood, but it’s thought to involve immune-mediated injury to hematopoietic stem cells or direct marrow toxicity, leading to a drop in all cell lines.

In contrast, clozapine is best known for agranulocytosis (a severe drop in neutrophils) rather than aplastic anemia, though any drug with hematologic toxicity requires vigilance. Other antipsychotics like haloperidol, risperidone, quetiapine, and ziprasidone have much lower or less clearly documented associations with aplastic anemia, making the combination of chlorpromazine and trifluoperazine the most recognizable pair for this adverse effect. If such symptoms or abnormal CBC results occur in a patient on these drugs, urgent evaluation and discontinuation of the offending agent are essential.