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Psychoactive Medications and Risk of Delirium in Hospitalized Cancer Patients

From the Centre de Recherche en Cancérologie de L'Hôtel-Dieu de Québec; Department of Psychiatry, L'Hôtel-Dieu de Québec; Centre Hospitalier Universitaire de Québec; Faculties of Pharmacy and Medicine and Department of Psychiatry, Faculty of Medicine, Laval University; Maison Michel Sarrazin; and Centre de Recherche Université Laval Robert-Giffard, Québec City, Québec, Canada

Address reprint requests to Pierre Gagnon, MD, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, 11 Côte du Palais, Québec City, Québec, Canada G1R 2J6; e-mail: pierre.gagnon{at}crhdq.ulaval.ca

PURPOSE: Psychoactive medications are biologically plausible and potentially modifiable risk factors of delirium. To date, however, research findings are inconsistent regarding their association with delirium. The association between exposure to anticholinergics, benzodiazepines, corticosteroids, and opioids and the risk of delirium was studied.

PATIENTS AND METHODS: A total of 261 hospitalized cancer patients were followed up with repeated assessments by using the Nursing Delirium Screening Scale for up to 4 weeks for incident delirium. Detailed exposure to psychoactive medications was documented daily. Strengths of association with delirium were expressed as hazard ratios (HRs) in univariate and multivariate analyses by using Cox regression models. All medication variables were coded as time-dependent covariates. Whenever possible, exposure was computed by using cumulative daily doses in equivalents; dichotomous cutoffs were determined.

RESULTS: During follow-up (mean, 8.6 days), 43 patients became delirious (16.5%). Delirium was associated with a history of delirium and the presence of hepatic metastases at admission. Analysis of the effect of medications was performed adjusting for these factors. Patients exposed to daily doses of benzodiazepines above 2 mg (HR, 2.04; 95% CI, 1.05 to 3.97), above 15 mg of corticosteroids (HR, 2.67; 95% CI, 1.18 to 6.03), or above 90 mg of opioids (HR, 2.12; 95% CI, 1.09 to 4.13) had increases in the risks for delirium. We did not observe associations between anticholinergics and risk for delirium.

CONCLUSION: Exposure to opioids, corticosteroids, and benzodiazepines is independently associated with an increased risk of delirium in hospitalized cancer patients.

Supported by a grant from the Sociobehavioural Cancer Research Network, funded through the National Cancer Institute of Canada (NCIC) Centre for Behavioural Research and Program Evaluation, with funds from the Canadian Cancer Society. J.-D.G. is the recipient of a Fonds d'Enseignement et de Recherche Award from the Faculty of Pharmacy, Laval University, and of a Canadian Institutes of Health Research-NCIC award from the Strategic Training Program in Palliative Care Research. P.G. is a research scientist of the Canadian Cancer Society through an award from the NCIC, and M.-A.R. is a senior research scientist (Chercheur-Boursier) supported by the Fonds de la Recherche en Santé du Québec (Montreal). M.-A.R. is also the recipient of a Clinical Scientist Award from the Fonds de la Recherche en Santé du Québec.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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