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Am Fam Physician. 2004;69(3):631-633

Alzheimer's disease is a progressive disorder with a substantial impact on patients and their families. Approximately 90 percent of patients with Alzheimer's disease have some form of neuropsychiatric disorder, most commonly depression. Approximately 20 to 25 percent of patients with Alzheimer's disease have major depression, and another 20 to 30 percent have other depressive syndromes. In patients with Alzheimer's disease, depression can have a substantially negative impact on quality of life and ability to perform activities of daily living (ADLs), and can increase the likelihood of physical aggression, being discharged from assisted-living facilities, entering nursing homes at earlier stages, and greater caregiver burden. Current studies on the benefit of treating depression in patients with Alzheimer's disease are limited by the small numbers treated and short follow-up periods. Lyketsos and associates studied the safety and effectiveness of sertraline in the treatment of major depression in patients with Alzheimer's disease. They also evaluated the secondary benefits of depression reduction in this treatment regimen.

Patients who had a diagnosis of probable Alzheimer's disease based on established criteria and a score of 10 or more on the Mini-Mental State Examination were enrolled in this randomized, placebo-controlled, parallel, 12-week trial. They also had to meet the diagnosis of major depressive disorder based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., and be in stable physical health. Before initiation of the study, each participant's depression was rated using the Hamilton Depression Rating Scale. Patients were assigned randomly to receive placebo or sertraline starting at 25 mg per day and titrating up to a maximum dosage of 150 mg per day or the highest tolerated dosage. Follow-up evaluation was performed every three weeks during the study, and adverse effects and events were recorded at each follow-up encounter. Main outcome measures included the response rate to treatment and changes in the various scales performed at baseline.

Among the patients taking sertraline, 38 percent (nine patients) had a complete response, and 46 percent (11 patients) had a partial response. The response rates were significant when compared with the response rates of patients in the placebo group. There were no significant differences in Mini-Mental State Examination scores between the two groups at the end of the study. Full or partial responders in the sertraline treatment group had significantly better ratings on ADLs, behavior disturbances, and caregiver stress when compared with the placebo group. Few patients in the sertraline treatment group dropped out of the study because of adverse effects, and there were no significant differences in the rate of adverse events between patients taking sertraline and those taking placebo.

The authors conclude that sertraline is superior to placebo in the treatment of major depression in patients with Alzheimer's disease. Reduction of depression in this group is associated with a reduction in behavior disturbances, improvement in the ability to perform ADLs, and reduction of caregiver stress. Treatment of depression with sertraline does not improve cognitive function.

editor's note: In the tradition of mind-body interaction in all medical illnesses, Lyketsos and associates found that treating depression in patients with Alzheimer's disease can have a significant impact on the well-being of these patients. They also found that treatment of depression can reduce caregiver stress. This reduction in stress can improve quality of life in those who provide care for patients with Alzheimer's disease. Caregiver issues related to patients who have Alzheimer's disease can be overwhelming. This study suggests a way to reduce this stress by treating the underlying depression of patients with Alzheimer's disease.—K.E.M.

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