A 31-year-old man is brought to the office by his father due to behaving bizarrely and hearing voices. Over the past month, the patient has locked his bedroom door at night and has refused to drink the tea that his mother prepared. He believes that she has been replaced by an imposter and is trying to poison him. When interviewed alone, the patient says, "People are trying to control me through a chip that was implanted in my brain." The patient was hospitalized for an acute psychotic episode at age 27. He was successfully treated with haloperidol, but he discontinued the medication after experiencing muscle spasms in his neck, restlessness, and difficulty sitting still. Medical issues include type 2 diabetes mellitus and seasonal allergies. Physical examination is unremarkable and urine drug screening is negative. Which of the following is the most appropriate pharmacotherapy for this patient?
This patient is acutely psychotic and requires prompt treatment with antipsychotic medication. Although he responded to haloperidol during his previous episode, he experienced major tolerability issues due to extrapyramidal symptoms (EPS) (eg, acute dystonic reaction, akathisia), which likely contributed to his subsequent nonadherence. EPS are more common with high-potency, first-generation antipsychotics such as haloperidol due to their potent dopamine D2 antagonism in the nigrostriatal pathway.
The best approach in this patient would be to treat with a second-generation antipsychotic (eg, ziprasidone) as it reduces the risk of EPS. Among the second-generation antipsychotics, ziprasidone has a low metabolic risk profile, whereas olanzapine is associated with the highest risk of weight gain and metabolic side effects (eg, insulin resistance, hyperlipidemia) and should be avoided in this patient due to his history of type 2 diabetes (Choice D). Other second-generation antipsychotics with lower metabolic risk include aripiprazole and lurasidone.
(Choice A) Although clozapine causes virtually no EPS, it is reserved for patients who have failed at least 2 antipsychotic trials due to the risk of agranulocytosis. It is also associated with significant risk of weight gain and metabolic side effects.
(Choice B) Switching to another high-potency, first-generation antipsychotic such as fluphenazine may result in similar side effects (ie, EPS) and again lead to nonadherence.
(Choice C) Switching to the long-acting injectable form of haloperidol would be indicated if the patient were nonadherent and had no tolerability issues on oral haloperidol.
Educational objective:
Compared with first-generation antipsychotics, second-generation antipsychotics cause fewer extrapyramidal symptoms but are associated with metabolic effects to varying degrees. Clozapine and olanzapine carry a high risk of metabolic side effects, whereas ziprasidone, aripiprazole, and lurasidone are associated with the lowest risk.