Lorazepam-Induced Toxicity in the Aged

Long-Term Lorazepam Use and Acute Toxicity in the Aged

This study will compare the effects of an acute dose of lorazepam to a placebo in elderly patients with generalized anxiety disorder (GAD).

GAD is among the most common anxiety disorders in the elderly population. The drug lorazepam is widely utilized in the treatment of elderly individuals with GAD. However, single doses of lorazepam have been associated with cognitive toxicity that is typically evident between 1 and 2.5 hours after the drug is administered. The toxic effects include decreased memory and increased swaying, which has been associated with greater risk for falls.

Patients have 4 study visits. A psychiatric evaluation and a memory test are given at the first visit. During the second study visit, patients have a physical exam, an electrocardiogram (ECG), a neuropsychological assessment, an optional magnetic resonance imaging (MRI) brain scan, and other laboratory tests. On the third and fourth visits, patients are randomized to receive either their highest daily dose of lorazepam or placebo. Performance effects and postural sway are determined before drug administration and at 1, 2.5, and 5 hours after the drug is given. Blood samples for the determination of drug levels are also obtained.

Inclusion Criteria:

• Lorazepam treatment for at least 3 months
• Cognitively intact

Note: Individuals who are unable or unwilling to have an MRI may be included

Exclusion Criteria:

• Major psychiatric disorder other than GAD
• Significant medical illness which may increase the likelihood of adverse reactions to lorazepam
• Severe loss of hearing or vision
• Current or past history of alcohol dependence
• Substance abuse within the past 6 months
• MRI evidence of infection, infarction, or other lesions suggestive of intervening neurological disease
• Clinical symptoms that suggest neurological disease
• Dementia or other mental syndromes or disorders