Which antipsychotic has the highest risk of weight gain among common second-generation agents?

Which antipsychotic has the highest risk of weight gain among common second-generation agents?

• A. Olanzapine
• B. Ziprasidone
• C. Aripiprazole
• D. Lurasidone

Answer: (A)

Weight gain risk with second-generation antipsychotics is closely tied to how strongly a drug blocks certain receptors that regulate appetite and metabolism. Olanzapine has particularly potent blockade of histamine H1 and serotonin 5-HT2C receptors, which increases appetite and promotes weight gain and metabolic changes. This combination makes it the antipsychotic with the highest weight-gain risk among common SGAs. The other options—ziprasidone, aripiprazole, and lurasidone—tend to have more favorable metabolic profiles: ziprasidone is often weight-neutral or may even cause weight loss, aripiprazole is typically weight-neutral, and lurasidone shows only modest weight gain. In practice, if weight gain is a major concern, clinicians may prefer agents with lower metabolic risk and should monitor weight, glucose, and lipids regularly. Clozapine can have even greater weight gain, but it isn’t in this list.

Weight gain risk with second-generation antipsychotics is closely tied to how strongly a drug blocks certain receptors that regulate appetite and metabolism. Olanzapine has particularly potent blockade of histamine H1 and serotonin 5-HT2C receptors, which increases appetite and promotes weight gain and metabolic changes. This combination makes it the antipsychotic with the highest weight-gain risk among common SGAs. The other options—ziprasidone, aripiprazole, and lurasidone—tend to have more favorable metabolic profiles: ziprasidone is often weight-neutral or may even cause weight loss, aripiprazole is typically weight-neutral, and lurasidone shows only modest weight gain. In practice, if weight gain is a major concern, clinicians may prefer agents with lower metabolic risk and should monitor weight, glucose, and lipids regularly. Clozapine can have even greater weight gain, but it isn’t in this list.