Atypical antipsychotics and delirium in critical care

Wan and colleagues (Critical Care 15:R159) recently reported a case series of patients with refractory delirium successfully treated with the atypical antipsychotic drug quetiapine. This class of medication is used infrequently by critical care physicians at present and offers a potentially useful treatment for a group of patients who are clinically challenging to manage. However, larger studies are required to evaluate both efficacy and adverse events in a critically ill population.

Wan and colleagues recently reported a case series of patients with refractory delirium successfully treated with the atypical antipsychotic drug quetiapine. Th is class of medication is used infrequently by critical care physicians at present and off ers a potentially useful treatment for a group of patients who are clinically challenging to manage. However, larger studies are required to evaluate both effi cacy and adverse events in a critically ill population.
Wan and colleagues reported a case series of 17 patients with refractory delirium treated with the atypical anti psychotic quetiapine [1]. A reduction in the concomitant use of other medications and resolution of delirium was observed. A contemporary survey of UK physicians found haloperidol was the treatment of choice for fi rst-line (74%) and second-line (34%) management of hyper active delirium [2]. Atypical antipsychotics were rarely used for fi rst-line treatment of hyperactive delirium and were used by just over 10% of physicians as second-line treatment [2].
Treating patients with delirium is challenging and atypical antipsychotic drugs have fewer extrapyramidal side eff ects than haloperidol. Wan and colleagues ob served increased somnolence and transient hypo tension associated with quetiapine administration [1]. However, larger studies are required to adequately assess both effi cacy and adverse eff ects in critically ill patients. Most adverse event data originate in patients with psychiatric disease and include agitation, tachycardia, hypotension (especially in the elderly), QT prolongation, tardive dyskinesia, malignant neuroleptic syndrome, extra pyra midal eff ects, hepatitis, hyperglycaemia, hyponatraemia, dyslipdaemia, thromboembolism, pneumonia, and increased mortality in elderly patients with dementia-asso ciated psychosis. Th ese side eff ects may be more signifi cant in critically ill patients with limited physio logical reserve. Moreover, as atypical antipsychotics are extensively metabolised by cytochrome P-450, the potential for drug interactions increases, leading to either toxic or subtherapeutic levels [3]. Paradoxical agitation may be observed during initiation and rapid dose escala tion with quetiapine [4]. Th is phenomenon is well des cribed with benzodiazepines [5], which are used fre quently for the second-line management of hyperactive agitation [2], and requires further characterisation in the critically ill.

Cathrine A McKenzie, Ruth YY Wan and Nicholas A Barrett
We thank Dr Wise and colleagues for their insightful comments. We agree that our retrospective case series provides useful research-generating data. We look forward to participating in future randomised controlled studies of atypical antipsychotics in the critically ill.
With regards to their comments on side eff ects, only limited sedation and transient hypotension were observed in the reported case series. Paradoxical agita tion was not observed in the 17 patients described, and indeed has not been noted in further restricted use of quetiapine within the critically ill at Guy's and St Th omas' NHS Foundation Trust. Whether this is because of the low doses of quetiapine used, the inherent bias that exists in retrospective observational studies or the small number of patients studied is diffi cult to fully establish. A single case of QT prolongation was described in the series and this was in association with the potential interacting agent fl uconazole [1]. As with all prescriptions for agents where there is a risk of an interaction that can result in prolongation of QT, careful prescription assessment by the multidisciplinary team and regular 12-lead electrocardiograms may help minimise risk of drug-drug interactions and potential patient harm [6,7].