Auditory musical hallucinations associated with extended-release pramipexole in an elderly patient with Parkinson's disease.

Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in Parkinson's disease (PD) that have been limited previously. The characteristics of AMHs in PD remain uncertain. We describe a 72-year-old woman with PD who presented with AMHs. The AMHs occurred after immediate-release pramipexole was switched to extended-release pramipexole. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. The music was unpleasant, but not objectionable, threatening, or ego-syntonic, and it did not interrupt her daily activities. AMHs in PD were non-threatening, and dopaminergic treatment may predispose patients to AMHs or be a unique possible cause of AMHs. The hallucinations can occur after immediate-release pramipexole was switched to extended-release pramipexole.

INTRODUCTION

Hallucinations, predominantly visual in nature, can occur in Parkinson disease (PD) and are often related to the antiparkinsonian drugs. Visual hallucinations are a well-recognized problem. Besides visual hallucinations, patients with PD uncommonly experience different forms of hallucinations, such as auditory hallucinations. Auditory hallucinations occur in 8% to 13% of patients with PD and are generally accompanied by visual hallucinations. Most auditory hallucinations are a repetitive human voice.[1] Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in PD that have been reported in only 8 patients.[2-6] Four patients for whom detailed information is available have been documented,[2-5] and 2 of these patients were deaf[2,4] (Table 1). In patients with AMHs caused by conditions other than PD, AMHs are characterized by repetitive and usually uncontrollable musical patterns, unrelated to external stimulation. However, the characteristics of AMHs in PD remain uncertain. We describe a patient with PD who presented with AMHs.

TABLE 1

Auditory Musical Hallucinations in Previous Patients With Parkinson Disease

CASE REPORT

In December 2005, a 72-year-old right-handed woman with no clinically significant history of disease, including epilepsy, migraines, or mental disease such as schizophrenia, noticed a tremor in her right hand. In December 2007, she noted slowness of movement, difficulty in walking in narrow spaces, and the onset of left hand tremor in addition to right hand tremor and presented at our hospital. She showed features of moderate Parkinsonism, including masked face, retropulsion, bradykinesia, and right-side-dominant rigidity and resting tremor. The scores on parts I, II, III, and IV of the unified Parkinson disease rating scale (UPDRS) were 0, 14, 24, and 0, respectively. The scores on the Mini-Mental Status Examination (MMSE) and Frontal Assessment Battery were normal (30/30) and decreased (16/18), respectively. The results of magnetic resonance imaging (MRI) of the brain were normal. She was given levodopa (250 mg/day) and immediate-release pramipexole (1.5 mg/day), and the severity of these symptoms had decreased in May 2008. In August 2008, she showed wearing-off phenomenon and had freezing of gait. The dose of levodopa was consequently increased to 500 mg/day. Subsequently, she was given entacapone (200 mg/day) in June 2010 and zonisamide (25 mg/day) in July 2011. The score on UPDRS part III was 12. The scores on the MMSE and Zung depression scale were 29 and 45, respectively. In July 2012, selegiline (5 mg/day) was started since the severity of freezing gait had intensified, and the patient frequently fell. She was then given stable doses of levodopa (500 mg/day), immediate-release pramipexole (1.5 mg/day, 3 times per day), entacapone (200 mg/day), zonisamide (25 mg/day), and selegiline (5 mg/day). Neuroleptic drugs were not used. In December 2012, we switched from immediate- to once-daily extended-release pramipexole in stable dosage because off-periods had increased. After that, she often had visual hallucinations such as animals or human hands and auditory hallucinations such as rustling sounds. In April 2013, AMHs solely occurred. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. AMHs did not occur every day, but when they did the music persisted all day while the patient was awake. She could not reproduce or stop the music. The AMHs were unrelated to visual hallucinations as well as other auditory hallucinations of children talking together. The music was unpleasant, but not objectionable, threatening or ego-syntonic, and it did not interrupt her daily activities. She had no hearing loss or history of using a hearing aid. The MMSE score was 28. Although the hallucinations persisted, she requested no further measures to suppress the hallucinations, such as the reducing the doses of anti-parkinsonian drugs or using neuroleptic agents, because the hallucinations were non-threatening and tolerable. In October 2013, zonisamide was increased to 50 mg/day because off-periods had increased. The score on part III of the UPDRS was 14. After receiving the patient's informed consent, we switched back from extended- to immediate-release pramipexole in a stable dosage in January 2014 to determine whether extended-release pramipexole was causing the AMHs. When the patient visited to our hospital 5 day after switching back to immediate-release pramipexole, she reported that recognizable subjects such as animals or persons that she previously saw clearly as visual hallucinations had disappeared, whereas some unrecognizable shadows were often evident. AMHs sometimes occurred for several hours, particularly in the early morning or evening, and other auditory hallucinations became faded. Twelve days after retuning to immediate-release pramipexole, visual hallucinations rarely occurred, and AMHs and other auditory hallucinations had disappeared.

DISCUSSION

Among the 5 patients including ours[2-5] for whom detailed information are available, AMHs in PD were non-specific incomprehensible tunes or different familiar or popular songs such as folk or lyrical songs, which were unrelated to an external stimulus. AMHs were absent during sleep and were not related to visual hallucinations. The inability of patients to interrupt AMHs might have been uncomfortable, but was not threatening.

Female sex, hearing impairment, advanced age, psychiatric conditions, cognitive disorders, alcoholism, obsessive–compulsive disorders, and neurological conditions (eg, seizure disorders, stroke, tumors, central nervous systems infections, and brain lesions in the dorsal pons, temporal lobes, and frontal lobes) were reported as risk factors for AMHs.[3] Our patient had none of these risk factors except for female sex and advanced age. In the 5 patients including ours,[2-5] neither cognitive decline nor depression was evident during AMHs, and disease severity and off-periods were apparently unrelated to AMHs. The intervals between the time of altering treatment with anti-parkinsonian drugs and the onset of AMHs were long in 2 previous patients, and the authors did not mention any relation between AMHs and anti-parkinsonian drugs.[2,3] In another patient, however, short-term AMHs were elicited by amantadine.[4] In our patient, although other preceding dopaminergic treatments such as levodopa, entacapone, and selegiline might have been prerequisite to the development of the hallucinations, the auditory and visual hallucinations occurred after immediate-release pramipexole was switched to extended-release pramipexole, and similar findings have not been reported previously. Several months after that, AMHs began. In studies of patients with advanced[7] or early PD,[8] switching from immediate- to extended-release pramipexole was safe, and the most frequently reported side effects were dyskinesia or somnolence. In healthy male volunteers, the pharmacokinetics and tolerability of a once-daily extended-release formulation of pramipexole were similar to those of an immediate-release formulation of pramipexole given 3 times daily.[9] However, 2 patients with PD in whom dopamine dysregulation syndrome developed after switching from immediate-release to extended-release pramipexole have been reported.[10] AMHs in PD were non-threatening, and dopaminergic treatment may predispose patients to AMHs or be a unique possible cause of AMHs.