Abstract
Abstract
The patient was a 57-year-old woman with malignant pleural mesothelioma. She had a past history of anxiety neurosis but not had any history of otological diseases. On admission to our hospice (day 1), she complained of dyspnea and wheezing associated with the progression of her underlying disease. After we started oral betamethasone (2 mg/d), dyspnea was alleviated and the frequency of wheezing was reduced. On day 3, she began to experience musical hallucinations that were manifested in opera/piano concert music and a child's voice. The episodes of musical hallucinations occurred approximately 10 times a day and disappeared spontaneously within several minutes. She had not experienced these symptoms before. We reduced the dose of betamethasone to 1 mg/d, but the musical hallucinations continued. Then on day 11, we switched betamethasone (1 mg/d) to prednisolone (10 mg/d) and we then gradually tapered off prednisolone. The frequency of musical hallucinations decreased and she ceased to experience musical hallucinations on day 29. However, on day 40, her dyspnea was aggravated again, so we started treatment with prednisolone (5 mg/d). Dyspnea was alleviated and no musical hallucinations occurred. On Day 51, dyspnea was worsened and we switched prednisolone to betamethasone (4 mg/d), which she hoped to use. The betamethasone alleviated the dyspnea but she developed musical hallucinations that were similar to the previous episodes. The musical hallucinations disappeared spontaneously 4–5 days later without changing the betamethasone. Musical hallucinations never occurred thereafter. She later died due to the exacerbation of disease.
Introduction
Case Report
The patient was a 57-year-old woman who had been a piano instructor for many years. She had no prior history of any psychiatric illness or symptoms. At approximately the age of 40, she experienced physical and psychological stress related to caring for her husband's elderly mother. Her relationship with her son was strained because of difficulties related to his university admission and she suffered from psychological stress due to her husband's transfer to another office. As a result, she began to repeatedly develop symptoms such as hyperventilation, numbness of the fingertips, and trembling. She was diagnosed with anxiety neurosis at a psychiatric clinic and was treated with medication. She was so depressed that she had to be hospitalized some time. During the course of the treatment, she had mood swings that indicated the presence of bipolar disorder. Olanzapine was prescribed for this condition. She did not report hallucination or delusions at that time. She had no history of otorhinological disease or hearing loss.
She was noted to have a small effusion on the right side of her chest in 2005 but the cause was not identified. In 2006, a biopsy was performed, which was read as showing reactive mesothelial cell proliferation. She was followed closely, receiving thoracic drainage at intervals of every 2 or 3 months. Another biopsy was performed, with the pathology now showing malignant pleural mesothelioma in February 2008. A thoracoabdominal shunt was inserted on her right chest to manage her pleural effusion. Because of the intractable pleural effusion, she underwent bilateral pleurodesis (pleural adhesion). Chemotherapy was administered, but with poor response. A pericardial effusion was revealed by echocardiography but drainage was not thought to be indicated. She developed precordial pain, facial edema, wheezing, and dyspnea. She was then admitted to our hospice in February 2009.
On admission, she complained of dyspnea and wheezing. Oxygen (4 L/min) was transnasally administered and percutaneous oxygen saturation was 95% (SpO2). Dry rales were heard at the end of expiration. The chest computed tomography (CT) revealed tracheal compression and small amounts of bilateral pleural effusions. Attacks of wheezing occurred sporadically every 2–3 days and they subsided after intravenous infusion of diprophylline (150 mg) and hydrocortisone sodium succinate (300 mg). She received a fentanyl patch (25 μg/hr), diclofenac (75 mg/d), olanzapine (25 mg/d), paroxetine (20 mg/d), trazodone (25 mg/d), bromazepam (1 mg/d), furosemide (20 mg/d), carbocysteine (150 mg/d), famotidine (40 mg/d), and teprenone (150 mg/d).
On the second day, oral betamethasone (2 mg/d) was started to alleviate her dyspnea and wheezing. However on the third day, she began to experience auditory hallucinations that manifested in the form of opera/piano concert music, chorus of male voices, and female singing voices. The episodes of musical hallucinations occurred about 10 times per day and disappeared spontaneously within several minutes. She also had tactile hallucinations as if someone had tapped on her shoulder. Her cognition and mood was normal at that time. She had not experienced these symptoms before and her previous physician reported that no hallucinations had been observed before. She was not distressed by these hallucinations. Her dyspnea subsided and her wheezing disappeared. Therefore, we reduced the dose of betamethasone to 1 mg/d on the seventh day. However, the musical hallucinations continued to occur. On the eleventh day, we switched the betamethasone (1 mg/d) to prednisolone (10 mg/d). The episodes of musical hallucinations decreased gradually. On the fifteent day, we reduced the prednisolone to 5 mg/d. From the eighteenth day on, the voices and sensation of someone tapping on her shoulder were no longer reported and the music was the only component of musical hallucinations. On the twenty-fourth day, prednisolone was discontinued. She ceased to experience musical hallucinations from the twenty-ninth day onwards.
Thereafter, her respiratory symptoms remained stable, but her dyspnea worsened on the thirty-ninth day. We discussed the risk of relapse of musical hallucinations with her before commencing retreatment with corticosteroids. She preferred alleviation of dyspnea to avoidance of musical hallucinations. On the fortieth day, we resumed treatment with prednisolone (5 mg/d). No musical hallucinations occurred and dyspnea was relieved for a moment. However dyspnea worsened on the fifty-first day and we switched the prednisolone to betamethasone (4 mg/d). The betamethasone treatment alleviated the dyspnea but she again developed musical hallucinations with voices. They occurred approximately 10 times per day and disappeared spontaneously within several minutes. She reported that the musical hallucinations were less uncomfortable than before. The musical hallucinations disappeared spontaneously 4–5 days later without drug change (Fig. 1). Musical hallucinations never occurred thereafter. Her condition deteriorated gradually and she died peacefully with palliative sedation later.
Clinical course.
Discussion
We believe this is the first reported case of steroid-induced musical hallucinations, which were relieved by “steroid switching.” Musical hallucinations are described as the perception of melodies including harmony, rhythm, and tone in the absence of actual external acoustic stimuli. They are manifested in the form of childhood, religious, patriotic, or operatic tunes that had been heard during childhood.5–7 In a large survey at a general hospital, the prevalence rate of musical hallucinations was 0.16%. 8 However the prevalence varies according to the previous reports. For example, a study in an audiological clinic reported a 2.5% prevalence of musical hallucinations among nonpsychiatric patients. 9
The cause of musical hallucinations remains unclear. According to recent studies using single-photon emission computed tomography (SPECT) or positron emission tomography (PET), patients experiencing musical hallucinations showed increased metabolism in the superior temporal cortex, parasagittal occipital cortex, thalamus, or bilateral basal ganglia 10 ; increased blood flow through the right superior temporal and the right inferior frontal gyri 11 ; increased activities of the right basal ganglia, right frontal operculum, posterior temporal lobes (especially right), both lobes of cerebellum, left deep sylvian cortex or left frontal lobe 12 ; and increased blood flow through the left temporal regions or left angular gyrus. 13 However, these studies demonstrated that subjects have varied features to their hallucinations and therefore the results do not suggest a consistent relationship between any particular brain region and musical hallucinations.
The risk factors for musical hallucinations include (1) advanced age, (2) female gender, (3) auditory disorders (tinnitus, hyperacusis, etc.), (4) neurologic disease (parkinsonism, epilepsy, cerebral infarction, cerebral aneurysm, infection of the central nervous system, local lesions affecting the dorsal side of pons, temporal lobe or frontal lobe, etc.), (5) psychiatric diseases (obsessive-compulsive disorder, depression, bipolar disorder, and anxiety disorder, delirium, dementia, etc.) and (6) medication (antidepressants, salicylates, benzodiazepines, triazolam, pentoxifylline, propranolol, amphetamine, quinine, phenothiazines, carbamazepine, marijuana, paracetamol, phenytoin, procaine, alcohol, general anesthesia, etc.), and (7) affinity for music.14,15 Evers et al. 16 classified the previously reported 132 cases of musical hallucinations according to their causes: hypacusis (52 cases), psychiatric disorder (31 cases), focal brain lesion (21 cases), epilepsy (15 cases), and intoxication (13 cases).
In this case, the first episodes of musical hallucinations appeared the day after the start of betamethasone and disappeared after the discontinuation of prednisolone. Subsequently the second episodes occurred after prednisolone was switched to betamethasone to alleviate the aggravation of dyspnea. Thus, in this case betamethasone usage was closely correlated with the occurrence of musical hallucinations. It is interesting to note that the type of steroid may influence the occurrence of musical hallucinations, given that in this case they were provoked by betamethasone but not by prednisolone. Theoretically the difference between chemical structures of the steroids leads to differences in steroid receptor affinities, resulting in differences in efficacy. Absorption and metabolism of steroids vary among individuals. For these reasons, the manner in which steroids manifest their therapeutic and adverse effects may differ even between 2 types of steroids having theoretically equivalent potency. The reason the musical hallucinations spontaneously disappeared, despite the continued use of betamethasone the second time it was used remains unclear.
The patient was not elderly and was free of auditory disorders. However she had multiple risk factors for musical hallucinations including (1) female gender, (2) psychiatric disease (anxiety neurosis and bipolar disorder), (3) multiple medications affecting the central nervous system (steroids, opioids, antipsychotics, antidepressants, benzodiazepines etc.) and (4) an affinity for music. Reported causes of drug-induced musical hallucinations include tricyclic antidepressants, carbamazepine, cannabinoids, paracetamol, phenytoin, baclofen, ketamine, and opioids (tramadol and oxycodone) which are often used in palliative care.17–21 Treatment with steroid-taper should be considered for steroid-induced psychiatric symptoms. 3 There is a report of the effectiveness of “steroid switching” in sterioid induced psychosis. 22
According to some case reports, musical hallucinations are seen in patients who are very familiar with music (e.g., musicians). 23 The patient worked as a piano instructor for many years and she had a high affinity for music. Other investigators reported that the levels of musical education did not correlate with the onset of musical hallucinations. 24 However an overwhelming majority of musical hallucinations involve perception of “very familiar melody or tone” rather a “melody or tone never heard before.”
In conclusion, in this case musical hallucinations were closely correlated with betamethasone usage and “steroid switching” was effective in treatment. We should not overlook musical hallucinations and their causes in psychiatric and palliative care settings.