A 63-year-old man with Parkinson disease, hypertension, and a history of depression returns to the office accompanied by his wife. His current medications include amantadine and carbidopa/levodopa, to which he has responded well, 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 initially he did very well after the recent dosage increase. They were able to partake in more social activities, dine out, and visit with friends, and the patient's falls became far less frequent. However, over the past week, she has become increasingly concerned about his 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 He has become more withdrawn and started to avoid his friends.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?

Question

A 63-year-old man with Parkinson disease, hypertension, and a history of depression returns to the office accompanied by his wife.  His current medications include amantadine and carbidopa/levodopa, to which he has responded well, 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 initially he did very well after the recent dosage increase.  They were able to partake in more social activities, dine out, and visit with friends, and the patient's falls became far less frequent.  However, over the past week, she has become increasingly concerned about his 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  He has become more withdrawn and started to avoid his friends.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?

Quizplus · Accepted Answer

Explanation: Most medications for Parkinson disease increase dopamine activity, either through direct receptor stimulation (eg, dopamine agonists, carbidopa/levodopa), decreased dopamine breakdown (eg, monoamine oxidase [MAO-B] inhibitors), or increased dopamine release (eg, amantadine). Other medications include anticholinergics (which can decrease acetylcholine effect in relation to dopamine effect) and catechol-O-methyl transferase (COMT) inhibitors, which can prolong levodopa's effect. Any medication that increases dopamine activity can cause psychotic symptoms. This patient has developed paranoid delusions and visual hallucinations following an increase in levodopa. Although dosage reduction or discontinuation of carbidopa/levodopa is an option (Choice D), this would not be the appropriate first step as this medication has significantly improved the patient's motor symptoms and quality of life. To maintain therapeutic effect, the least potent medications should be reduced or discontinued first, in the following order: anticholinergics, amantadine, MAO-B inhibitors, COMT inhibitors, dopamine agonists, and, finally, carbidopa/levodopa. The first step would be to reduce or taper off amantadine while maintaining the dosage of carbidopa/levodopa. Addition of low-dosage antipsychotics is indicated for medication-induced psychosis that persists despite adjustments to determine the minimum effective dosage of anti-parkinsonian medication. The low-potency second-generation antipsychotics quetiapine (Choice A) and clozapine have the lowest incidence of drug-induced parkinsonism and may be indicated. In contrast, potent D2 dopamine receptor antagonists such as first-generation antipsychotics and the second-generation antipsychotic risperidone (Choice B) should be avoided due to the risk of motor symptoms. Recently, pimavanserin, a serotonin 5HT-2A receptor inverse agonist, has been approved by the FDA for the treatment of psychotic symptoms in patients with Parkinson disease. (Choice C) Although this patient has a history of depression, his recent behavioral change is more consistent with psychosis than depression. His recent social withdrawal is most likely due to his increasing paranoia. Educational objective: Anti-parkinsonian medications can cause psychosis due to their dopaminergic effects. After ruling out dementia, delirium, or other medical etiologies for psychosis, the least potent medications should be withdrawn first before considering reducing carbidopa/levodopa. If psychosis continues despite adjustments of dopaminergic medications, quetiapine, clozapine, or pimavanserin should be considered. References: Psychosis in Parkinson disease: a review of etiology, phenomenology, and management. (http://www.ncbi.nlm.nih.gov/pubmed/27830568)

A 63-Year-Old Man with Parkinson Disease, Hypertension, and a History