Related to the New Topics Transient Amantadine-Induced Musical Hallucinations in a Patient with Parkinson ’ s Disease

Musical hallucinations are complex auditory hallucinations characterized by repetitive and usually uncontrollable musical patterns, unrelated to external stimuli. They are rare and can be induced by medications. Patients with Parkinson’s disease (PD) can experience different types of hallucinations, mostly visual, which can be related to the therapy or not. We report a patient with PD who developed musical hallucinations immediately after started taking amantadine. Part of this description has been reported in abstract form elsewhere. A 77-year-old woman presented with mild bradykinesia and left-side resting tremor, slowly progressive over 6 months. Neurological examination revealed normal, symmetric deep tendon reflexes, mild bradykinesia on finger tapping, rest tremor in the left hand, and a Mini Mental Status Exam score of 27/30. A head CT revealed mild atrophy. Early PD was diagnosed, but she refused to start medications. Three months later, after tremor worsening, she was started on pramipexole 0.125 mg BID, but developed gastric discomfort and vomiting, and was started on levodopa (100 mg) 1 benserazide (25 mg) TID. She had good control during 1 year, but experienced slight clinical worsening and was started on amantadine 100 mg TID. Two days later, she started to hear a sequence of four musical pieces (The Brazilian National Anthem, ‘‘Silent Night,’’ ‘‘Boi-da-Cara-Preta’’—an old Brazilian lullaby song, and ‘‘Olhos Verdes’’—a popular Brazilian musical piece from the mid XX Century). She denied psychiatric disease and previous episode of visual or auditory hallucination. She suffered from presbyacusis with occasional use of a hearing aid. She constantly heard this sequence of four musical pieces day and night, except during sleep. The Brazilian National Anthem and two other musical pieces were sung but she does not recall whether ‘‘Silent Night’’ was sung or played on an instrument. She was fully aware of the hallucinatory nature of the events and informed her family. She reported that the music was being played ‘‘inside her head,’’ not coming from the right or left ear. She could not interrupt the musical pieces by voluntary will or distraction. She did not try to interrupt the ongoing musical sequence by concentrating on another tune. One day after the hallucination onset, she quit amantadine. She continued to hear the same musical sequence for 3 days until spontaneous disappearance. A few days later, a follow-up EEG was normal. Amantadine was initially used in the treatment of respiratory infections caused by influenza A virus. It was subsequently found to exhibit antiparkinsonian effects. There is evidence that amantadine can rarely cause visual hallucinations and confusional state in elderly patients. To our knowledge, this is the first description of short-lived, transient, isolated musical hallucinations induced by amantadine. We observed a clear temporal relationship between the onset and disappearance of the hallucinations and amantadine administration. Although she was also taking levodopa, she was kept on the same dose for almost 1 year, without side effects. Although one cannot exclude a synergetic effect of levodopa 1 amantadine, the clinical course of the musical hallucinations (starting 2 days after amantadine initiation and disappearing 3 days after discontinuation) favors the hypothesis of amantadine induction. At any given time, about 25% of the patients with PD at different disease stages experience some form of auditory or visual hallucination, predominantly the latter. Most commonly, they are side effects of the antiparkinsonian treatment. However, musical hallucinations are much rarer than visual or pure auditory hallucinations in patients with PD. The etiology of musical hallucinations is unclear and different mechanisms are involved. Some medications are known triggers: benzodiazepines, propanolol, amphetamine, carbamazepine, salicylates, general anesthesia. There are several other risk factors reported: female gender, hearing impairment, advanced age, psychiatric conditions, cognitive disorders, and neurological conditions (e.g., seizure disorders, stroke, tumor, central nervous systems infections, and brain lesions in the dorsal pons, temporal lobes, and frontal lobes). Therefore, in addition to PD, our patient had other potential risk factors for musical hallucinations: presbyacusis, older age, female gender. Similar to other patients from the literature, the type of music heard during the hallucinations was patriotic or lyrical, and may be related to her childhood experiences. In summary, our findings suggest that musical hallucinations can be transiently induced by amantadine treatment in PD.