Neuroleptic Malignant Syndrome Caused by Quetiapine in an Elderly Man with Lewy Body Dementia.

Abstract

To the Editor: Elderly adults with Lewy body dementia (LBD) commonly present with behavioral and psychological symptoms of dementia (BPSD).1 Individuals with LBD can experience neuroleptic sensitivity especially to first-generation antipsychotics such as haloperidol.2 Atypical antipsychotics, especially quetiapine, which was thought to be safer, are often used to control BPSD in individuals with LBD.2 An elderly man with neuroleptic malignant syndrome (NMS), an extreme form of neuroleptic sensitivity, due to quetiapine was subsequently diagnosed with LBD. A 69-year-old man who was a nondrinker was admitted because of bizarre behavior (throwing household items) and personality change for 6 months. He had history of hypertension, hyperlipidemia, and ischemic heart disease with percutaneous coronary intervention. On physical examination, he was afebrile and had a blood pressure of 122/72 mmHg; there was no parkinsonism or focal neurological deficit. Cardiovascular, respiratory, and abdominal examinations were unremarkable. Blood tests including complete blood count and liver and renal function tests were unremarkable. Head computed tomography was normal. He was started on oral quetiapine 25 mg twice a day for behavioral control. He developed fever (temperature 38.8°C), tremor, and dysphagia on Day 4 after commencement of quetiapine. Physical examination was repeated and revealed tachycardia (113 beats/min), myoclonus, and parkinsonism. Investigations found leukocytosis (17 × 109/L) and high creatine kinase (4,064 U/L), but urine was negative for myoglobulin. Chest X-ray, urinalysis, nasopharyngeal aspirate, and cerebrospinal fluid examination were unremarkable. NMS due to quetiapine was diagnosed based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition,3 criteria, and quetiapine was immediately stopped. The man required transient tube feeding and intravenous fluid for hydration. Fever, tremor, tachycardia, myoclonus, and leukocytosis improved over the next few days, and creatine kinase normalized. Upon review of his cognitive history, he had had impairment of short-term memory for 1.5 years, with repetitive speech and confabulation. He had had visual hallucinations of seeing young girls and talking to these imaginary people, fluctuation of consciousness, and vigorous limb movement and yelling while asleep, which were suggestive of rapid eye movement (REM) sleep behavior disorder. He also had spatial and temporal disorientation and difficulty using the telephone and banking. His Mini-Mental State Examination score was 7 out of 30. Magnetic resonance imaging of the brain and electroencephalogram showed no evidence of Creutzfeldt-Jakob disease. 18-fluorodeoxyglucose positron emission tomography showed hypometabolism over the bilateral temporoparietal and occipital lobes. He fulfilled the diagnostic criteria of probable LBD.4 Upon discharge, he was prescribed donepezil 5 mg, valproate 150 mg twice a day, citalopram 10 mg, and clonazepam 0.5 mg to control his BPSD and REM sleep behavior disorder. Valproate was subsequently tapered. LBD is an α-synucleinopathy characterized by underlying Lewy bodies and Lewy neurites in the neocortex resulting in neuronal loss.5 It is thought that the extensive damage of dopaminergic and acetylcholinergic neurons contributes to the prominent BPSD and neuroleptic sensitivity.2 Neuroleptic sensitivity, which usually manifests as sedation, immobility, rigidity, postural instability, and confusion, affects 50% of individuals with LBD.2 NMS is a severe type of neuroleptic sensitivity usually caused by first-generation antipsychotics because of their high affinity to dopamine-2 (D2) receptors.2 The lower risk of atypical antipsychotics is thought to be related to lower affinity for D2 receptors and higher affinity for serotonin-2 receptors.2 Quetiapine has been regarded as one of the safest atypical antipsychotics. In a recent systematic review, quetiapine effectively reduced delusions, hallucinations, agitation, and aggression in individuals with LBD.6 The man described herein had a Naranjo scale score of 8, which corresponds to a probable adverse drug reaction,7 illustrating that quetiapine can cause NMS in individuals with LBD. Only one other case report of quetiapine-induced NMS in an individuals with LBD was identified.8 Other atypical antipsychotics that have been reported to cause NMS in individuals with LBD include olanzapine and resperidone.9, 10 Because of the incident of NMS, this man was not given antipsychotics. In a recent metaanalysis, donepezil has been found to improve cognition, hallucinations, delusions, and activities of daily living in individuals with LBD.6 Clonazepam, apart from treating REM sleep behavior disorder, has also been found to reduce sleep disturbance.6 There is limited evidence of the utility of citalopram and valproate in controlling BPSD of individuals with LBD and one of them was stopped subsequently.6 The BPSD of this man can be effectively controlled without any antipsychotic. In summary, quetiapine can cause NMS in individuals with LBD, although it is rare. There are other treatment options, such as anti-epileptics, benzodiazepines, and acetylcholinesterase inhibitors, for individuals with LBD with neuroleptic sensitivity to atypical antipsychotics in controlling BPSD. Conflict of Interest: The authors declare no competing interests. Author Contributions: Shea: study concept and design, acquisition of subjects and data: Both authors: analysis and interpretation of data, preparation of manuscript, critical review and approval. Sponsor's Role: None.