Abstract
Anti-psychotic medications are commonly used in aged psychiatry. Elderly patients are more sensitive to adverse effects especially cardiac complications, anti-cholinergic and extra-pyramidal side effects due to changes in receptors, volume distribution and increased number of concomitant medications [1]. We describe a case where an elderly man developed marked neuroleptic sensitivity despite the use of low dose atypical antipsychotics.
A 74 year old man with a history of depression was referred to an acute psychogeriatric inpatient unit with a one month history of confusion, depressed mood, poor appetite, insomnia, delusions of poverty and agitation. His medical co-morbidity included diabetes mellitus, as well as prostate and throat cancer which were in remission. Physical examination and organic workup was unremarkable apart from neuroimaging evidence of moderate ischaemia. A provisional diagnosis of psychotic depression was entertained and 15 mg of mirtazapine and 2.5 mg olanzapine was initiated. After three days, these medications were increased to 30 mg and 2.5 mg twice daily, respectively.
The following day he developed increased agitation, confusion, bradykinesia, increased tone and tachycardia. Creatinine kinase (CK) was found to be elevated at 1739. Psychotropic medication was ceased. Following neurological review, drug-induced Parkinsonism was diagnosed with the raised CK thought to be related to the rigidity. His CK returned to normal and the Parkinsonism improved; however, his mental state continued to fluctuate with ongoing psychotic symptoms, including now, visual and auditory hallucinations.
On transfer back to the acute aged psychiatry unit, quetiapine 25 mg twice daily was commenced. However, within 48 h he developed increased confusion, rigidity and a low grade fever. The CK rose to over 3000 and we diagnosed neuroleptic malignant syndrome (NMS). Quetiapine was ceased. He was transferred to an acute medical ward where following intravenous hydration and supportive management the CK returned to normal and the pyrexia and bradykinesia improved over the next week.
Following transfer to the psychogeriatric inpatient unit, we reviewed the history, diagnosis and management. Given the marked neuroleptic sensitivity, fluctuating cognition and visual hallucinations in particular, a clinical diagnosis of dementia with Lewy bodies (DLB) was considered. Donepezil 5 mg was prescribed and regular lorazepam added to assist with management of agitation. There was global improvement. However, ten days later he complained of headache, was drowsy and more confused. A CT scan revealed a large left parietal haemorrhage. He was transferred to a medical ward and died two weeks later.
This case highlights a number of issues related to use of anti-psychotics in general and in the elderly in particular. NMS, although historically a rare but serious side effect of typical anti-psychotic medication, occurs with atypical anti-psychotics as well and manifests in a similar way, the exception being clozapine which is less likely to manifest with prominent extra pyramidal symptoms [2]. One needs to be particularly vigilant with the elderly, given their increased sensitivity to adverse effects [1]. Neuroleptic sensitivity in DLB to typical and high potency atypical anti-psychotics has been reported including the potential to alter the course of the illness [3]. Low potency atypical anti-psychotics such as quetiapine are reported as being preferable in patients with DLB [4]. In this case, although the diagnosis of DLB was unable to be supported by neuropsychological assessment or functional neuroimaging, the marked neuroleptic sensitivity even on low dose quetiapine was striking.
Another contentious issue raised is the association with risperidone and olanzapine and increased vascular risk when used to treat the behavioural symptoms of dementia. Some have concluded that there is a two-fold increase in stroke and therefore should not be used in dementia [5]. Others have found no difference in stroke between typical and atypical anti-psychotics used in the treatment of dementia [6]. This case adds to the uncertainty.
Overall our case demonstrates the need for caution and an awareness of adverse effects even when following the principle ‘start low and go slow’ in this vulnerable patient population.