Question 1

A 35-year-old man with schizophrenia has been gaining weight steadily on olanzapine 20mg nightly for 2 years. He has gained 45 pounds, his fasting glucose is 118 mg/dL (pre-diabetic range), and his LDL is 165 mg/dL. He is psychiatrically stable with no psychotic symptoms. He asks if there is an antipsychotic that will not make him gain more weight. Which of the following is the most appropriate recommendation?

Accepted Answer

Answer A accepts ongoing metabolic harm without intervention; metabolic syndrome carries long-term cardiovascular morbidity and mortality. Answer C (adding metformin) is a reasonable adjunctive strategy and has some evidence, but it treats the consequence while continuing the cause; switching to a metabolically cleaner agent addresses the root problem. Answer D is incorrect: quetiapine has substantial metabolic effects (weight gain, glucose dysregulation), less severe than olanzapine but not a metabolically clean switch. The teaching point: when metabolic side effects are clinically significant and the patient is stable, a switch to a weight-neutral antipsychotic (ziprasidone, aripiprazole, lurasidone, cariprazine) addresses the problem more directly than adding metabolic medications to compensate for a metabolically harmful antipsychotic.

Question 2

A patient on ziprasidone 60mg BID presents for a routine follow-up. When asked about her medication routine, she reports taking both doses with coffee and a small granola bar (approximately 150 calories). She reports the medication "kind of works but not as well as my old medication." Ziprasidone was started 6 weeks ago after a switch from risperidone for weight gain. Psychotic symptoms have partially improved but she still hears occasional voices. What is the most likely explanation for the partial response?

Accepted Answer

This reinforces the food-absorption teaching point with a realistic clinical scenario. Answer A may ultimately be true but cannot be assessed until the medication is properly absorbed. Answer C is incorrect: 6 weeks is adequate for assessing antipsychotic response if the drug is being taken correctly. Answer D is pharmacologically nonsensical (QTc prolongation is a cardiac side effect, not an efficacy modifier). The teaching point: always verify food intake with ziprasidone before assessing efficacy. The 500-calorie requirement is a pharmacokinetic threshold, not a suggestion. A 150-calorie snack is not sufficient.

Question 3

An emergency department physician asks a consulting psychiatrist whether IM ziprasidone or IM olanzapine is safer for an acutely agitated patient who just received lorazepam 2mg IM ten minutes ago. The patient remains agitated. What is the correct recommendation?

Accepted Answer

This tests the IM olanzapine + IM benzodiazepine contraindication (also taught on the haloperidol page) and positions ziprasidone IM as a safe alternative. Answer A is dangerous because IM olanzapine after IM benzodiazepine carries a documented risk signal. Answer C may delay necessary treatment in a patient who is actively agitated and at risk of harming self or others. Answer D is incorrect because haloperidol is not the only safe option; ziprasidone IM is also safe with benzodiazepines. The teaching point: when a benzodiazepine has already been given IM and additional antipsychotic is needed, choose haloperidol or ziprasidone, not olanzapine.

Ziprasidone

Side Effects Worth Knowing

QTc prolongation: the defining label concern

Weight neutrality: the defining advantage

Sedation: mild-moderate

EPS: low but present

Orthostatic hypotension: moderate

Nausea: possibly serotonergic

Prolactin elevation: mild

Rash: uncommon but reported

See This Medication in Action

References & Further Reading