Methylphenidate Treats Apathy in Parkinson's Disease

SIR: The word apathy derives from the Greek word pathos or passions.¹ A lack of interest or emotion is thus termed apathy. The usage of this term has come to include not just a lack of emotion but also a lack of motivation.² Apathy has been differentiated from major depressive disorder (MDD), another very common problem in Parkinson's disease (PD).³ Levy et al.⁴ demonstrated that apathy and depression did not covary in patients with various neurodegenerative disorders, including a subsample with PD. Aarsland⁵ examined the range of neuropsychiatric disturbances in PD, using the Neuropsychiatric Inventory, and concluded that 16.5% of 139 patients had apathy. Apathy has not been successfully treated with the use of conventional antidepressants and remains a particularly vexing problem.

Methylphenidate (MPH), a stimulant chemically related to amphetamine, works by inhibiting dopamine uptake.⁶ Its mode of action is not completely understood, but presumably it activates the brainstem arousal system and cerebral cortex to produce its stimulant effect. It has been used as an adjunct for depression and apathy in various medical illnesses.^7,8 MPH has also been shown to increase the motor effect of levodopa in PD.⁹ It has a short duration of action and is usually given every 4 hours. It begins to act almost immediately, and its effects should be evident within the first couple of days.⁷ We report a patient with Parkinson's disease and apathy who did not respond to antidepressant treatment but was successfully treated with MPH.

Case Report

An 82-year-old right-handed man was evaluated at our center for a history of shuffling gait and freezing when walking for the past 2 years. Initially diagnosed as having normal-pressure hydrocephalus because of this gait difficulty, mild memory impairment, and dilated ventricles, he received a ventriculoperitoneal shunt with improvement. He later developed symptoms suggestive of Parkinson's disease, including bradykinesia, hypomimia, and balance problems. His cognitive decline continued, and he developed depression and apathy. The depression was treated successfully with paroxetine 20 mg/day, but the apathy remained a problem. His wife and family described him as having little or no motivation and wanting to sit around in the house all day. He would take frequent naps. Formerly a researcher by profession, he was known to be an avid reader and premorbidly had taken part in conversations and discussions. All this had changed since the illness, and his family complained that he would not read books or newspapers anymore and almost never asked any questions or took part in family conversations. He would answer most questions with “I don't know” and seemed unable to “articulate his thoughts.” He was started on methylphenidate 5 mg twice daily after a baseline ECG revealed no abnormalities or tachycardia. Within a week, his wife and family reported a marked change in his behavior. He was described as being more alert, falling asleep less often, and expressing much more interest in people around him. He began to read the New York Times again after a hiatus of several years. He resumed extended conversations about what he read and would articulate his opinion about the news. He smiled more, was more pleasant, and his wife and children felt he was more easy to be around. He complained of no side effects to the medication and tolerated it well. His score on the motivation/initiative item of the mentation subsection in the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 3 to 0 (0=none; 4=complete loss of motivation). No sleep disturbance or loss of appetite was reported.

Comment

Although methylphenidate has been used successfully in the treatment of apathy in various neuropsychiatric illnesses, its use has not been described previously in Parkinson's disease. The effectiveness of MPH in our patient is unlikely to be simply a euphoriant effect, since such effect may be blunted in PD patients.¹⁰

The etiopathogenesis of apathy in Parkinson's disease is a matter of some debate. Mayeux et al.¹¹ have described a correlation between norepinephrine metabolites and cognitive measures of bradyphrenia, which suggests that apathy may be related to deficiencies in catecholaminergic pathways and the locus ceruleus. This may be the mechanism by which methylphenidate is effective in treating the symptoms of this syndrome. However, Bhatia and Marsden¹² found in their review that abulia or apathy was common in 28% of patients with caudate lesions that spared the lentiform nucleus and in 27% of patients with lesions of the globus pallidus that spared the putamen. Cummings¹³ has described a syndrome of apathy related to damage to the anterior cingulate circuit. Thus, the pathology of this complex syndrome is far from being understood, and further studies are needed both to elucidate this pathology and to delineate useful treatments.