Correlates of Anticholinergic Activity in Patients With Dementia and Psychosis Treated With Risperidone or Olanzapine

Benoit H. Mulsant, M.D.; Georges M. Gharabawi, M.D.; Cynthia A. Bossie, Ph.D.; Lian Mao, M.S.; Rick A. Martinez, M.D.; Larry E. Tune, M.D.; Andrew J. Greenspan, M.D.; Jeni N. Bastean, Pharm.D.; and Bruce G. Pollock, M.D., Ph.D.

Background: Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade.

Study Design: This was a 6-week multisite, randomized clinical trial. Subjects: Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone. Assessments: Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales.

Results: There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior.

Implications: Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

(J Clin Psychiatry 2004;65:1708-1714)

Received May 19, 2004; accepted Sept. 14, 2004. From Western Psychiatric Institute and Clinic, Department of Psychiatry, Division of Geriatric Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pa. (Drs. Mulsant and Pollock); Janssen Medical Affairs, L.L.C., Titusville, N.J. (Drs. Gharabawi, Bossie, Greenspan, and Bastean and Mr. Mao); Geriatric Research, Education, and Clinical Center, Pittsburgh Veterans Administration Health System, Pittsburgh, Pa. (Dr. Mulsant); Janssen Research Foundation, Titusville, N.J. (Dr. Martinez); and Wesley Woods Health Center of Emory University, Atlanta, Ga. (Dr. Tune).

This research was funded by Janssen Medical Affairs, L.L.C.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Benoit H. Mulsant, M.D., Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213(e-mail: mulsantbh@upmc.edu).