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Cognitive and Behavioral Effects of a Range of Doses

Pierre N. Tariot, MD; Trey Sunderland, MD; Herbert Weingartner, PhD; Dennis L. Murphy, MD; Martin R. Cohen, MD; Robert M. Cohen, MD, PhD

Arch Gen Psychiatry. 1986;43(8):727-732.

Abstract
• There have been conflicting reports on the effects of naloxone hydrochloride in patients with dementia of the Alzheimer type (DAT). In addition, none of the naloxone studies in DAT used doses of 2.0 mg/kg or more, the amount necessary to produce reliable cognitive and behavioral changes in young normal subjects. In a randomized, double-blind, placebocontrolled study, 12 patients with DAT were administered naloxone hydrochloride in doses of 5 µg/kg, 0.1 mg/kg, and 2.0 mg/kg, with detailed evaluation of its behavioral and cognitive effects using measures selected for their potential relevance to DAT and the known effects of blockade of endogenous opiate systems. None of the measures of motor performance, attention, memory, learning, or recognition showed improvement with naloxone. Increased inappropriate verbal productions were noted after 0.1 mg/kg of naloxone hydrochloride. Patients became irritably activated after this dose, which may account for the altered verbal behavior in this study and also for some of the changes suggesting cognitive improvement in prior studies. Differences in the sensitivity and dose dependency of the behavioral effects in patients with DAT compared with prior studies in young normal subjects merit further investigation.

Author Affiliations
From the Section on Clinical Neuropharmacology, Laboratory of Clinical Science (Drs Tariot, Sunderland, and Murphy), Laboratory of Psychology and Psychopathology (Dr Weingartner), and Section on Clinical Brain Imaging, Laboratory of Cerebral Metabolism (Dr R. Cohen), National Institute of Mental Health, Bethesda, Md; and the Ensor Foundation Research Laboratory, William S. Hall Psychiatric Institute, and Department of Neuropsychiatry and Behavioral Science, School of Medicine, University of South Carolina, Columbia (Dr M. Cohen).

Footnotes
Accepted for publication Sept 6, 1985.

Read in part before the annual meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, Dec 14, 1984.

Reprint requests to Section on Clinical Neuropharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bldg 10, Room 3D/41, Bethesda, MD 20205 (Dr Tariot).

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