Which antipsychotic is listed as treatment for treatment-resistant major depressive disorder?

• A. Ziprasidone
• B. Risperidone
• C. Quetiapine
• D. Olanzapine

Answer: (A)

Treating treatment-resistant major depressive disorder often involves augmenting an antidepressant with a second-generation antipsychotic to boost the antidepressant response. Ziprasidone is listed as an augmentation option because clinical trials have shown that adding it to an ongoing antidepressant can produce additional improvement in depressive symptoms compared with antidepressant therapy alone. Its action on multiple neurotransmitter systems—antagonism at serotonin 5-HT2A and dopamine D2 receptors, with some 5-HT1A activity—helps modulate mood pathways that may not be fully engaged by antidepressants alone. While other antipsychotics like quetiapine, olanzapine, and risperidone also have evidence for augmentation, ziprasidone is notable for a relatively favorable metabolic profile, though it requires caution for QT interval prolongation. In choosing among them, clinicians weigh efficacy data alongside patient-specific risks such as weight gain, diabetes risk, prolactin elevation, and cardiac effects.