Which combination requires monitoring for orthostatic hypotension?

• A. Clozapine and Olanzapine
• B. Quetiapine and Ziprasidone
• C. Aripiprazole and Paliperidone
• D. Iloperidone and Risperidone

Answer: (D)

Orthostatic hypotension stems from alpha-1 adrenergic blockade by certain antipsychotics, which causes blood pressure to drop when moving to an upright position. When two drugs with strong alpha-1 blocking effects are used together, the risk becomes additive, making monitoring essential.

Iloperidone and risperidone both have notable alpha-1 antagonism, and this risk is particularly pronounced during initiation or rapid dose changes. Using them in combination increases the potential for dizziness, lightheadedness, or fainting upon standing, so careful blood pressure monitoring and patient education are important, especially at the start and with titration. This is why this pairing requires monitoring for orthostatic hypotension.

Other options include agents with lower or less predictable effects on orthostatic blood pressure, so the emphasis on close monitoring is greatest with a combination of two medications known for strong alpha-1 blockade.