A 63-year-old man with Parkinson disease, hypertension, and a history of depression comes to the office with his wife for follow-up. Medications include amantadine and carbidopa-levodopa; the patient has responded well to the latter, in contrast to his insufficient response to previous medications prescribed for Parkinson disease. During his last visit, his dosage of carbidopa-levodopa was increased to target continued shuffling gait, rigidity, and frequent falls. The patient's wife says that he initially did very well afterward; they participated in more social activities, dined out, and visited with friends, and falls became far less frequent. However, over the past week, she has become increasingly concerned about the patient's behavior. He has become more withdrawn and started to avoid his friends. The patient falsely accused her of infidelity and suddenly refused to see his son, saying, "All he wants is to get his hands on my money." He also called the police on several occasions because he reported seeing strangers in his bedroom. The patient is afebrile; blood pressure is 114/76 mm Hg and pulse is 64/min. Physical examination shows mild rigidity and tremor, which have improved since his last visit. The remainder of the examination is unremarkable. He shows no signs of dementia, delirium, or infection. Which of the following medication adjustments would be most appropriate in management of this patient?
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Most medications for Parkinson disease (PD) increase dopamine activity through direct receptor stimulation (eg, dopamine agonists, carbidopa-levodopa), decreased dopamine breakdown (eg, monoamine oxidase type B [MAO-B] inhibitors), increased dopamine release (eg, amantadine), or a prolonged levodopa effect (eg, catechol-O-methyltransferase [COMT] inhibitors). Anticholinergics are also used to reduce acetylcholine's action in relation to the reduction in dopamine. Any medication that increases dopamine activity can cause psychotic symptoms, as seen in this patient with paranoid delusions and hallucinations following a dosage increase in carbidopa-levodopa.
In patients with PD and psychotic symptoms (not attributable to other causes such as infection or delirium), the least potent, least effective medications should be reduced or discontinued first to preserve therapeutic effect, in the following order:
Although dosage reduction or discontinuation of carbidopa-levodopa is an option, it is not an appropriate initial step because this medication has significantly improved the patient's motor symptoms and quality of life. Dosage modification is done by balancing tolerability of psychotic symptoms with control of motor symptoms.
(Choice A) Although this patient has a history of depression, the timing of his behavioral change and social withdrawal more likely results from psychosis than depression.
(Choice B) In situations in which psychosis remains despite adequate work-up and reduction of antiparkinson medications, antipsychotics with minimal D2 dopamine receptor antagonism (eg, quetiapine, clozapine, pimavanserin) may be indicated. In contrast, antipsychotics with more potent D2 antagonism (eg, risperidone) should be avoided due to the risk of worsening motor impairments.
(Choice C) When the etiology of psychosis is unclear, a stepwise de-escalation of antiparkinson medications is recommended to preserve therapeutic benefit as much as possible. Rapid reduction or withdrawal of dopaminergic therapy may cause unbearable rebound symptoms and can precipitate symptoms resembling neuroleptic malignant syndrome (eg, hyperthermia, muscular rigidity, altered consciousness, autonomic instability).
Educational objective:
Antiparkinson medications can cause psychosis due to their dopaminergic effects and should be withdrawn in order, starting with the least potent, least effective agent. If psychosis continues despite adjustments of dopaminergic medications, quetiapine, clozapine, or pimavanserin can be considered.