VAS-COG: Sertraline Shows Promise for Improving Executive Function in Dementia

SAN ANTONIO, July 16 -- High-dose therapy with the selective serotonin reuptake inhibitor (SSRI) sertraline resulted in statistically and clinically significant improvement in isolated impaired executive function in older patients.

Among 37 patients treated, 23 (62.1%) had clinically meaningful improvement, defined as a decrease of more than three points on the EXIT25 measure of executive function. Thirteen patients met EXIT25 criteria for clinical remission, according to results of a small retrospective study reported here at the International Society for Vascular Behavioral and Cognitive Disorders meeting.

"Our mean improvement [on the EXIT25] is almost six points, which is the difference between two levels of care in a retirement community," said Donald R. Royall, M.D., of the University of Texas Health Science Center at San Antonio.

The patients were treated as part of a therapy evaluation program for patients with impairment involving the frontal lobe. Dr. Royall and colleagues used the Mini-Mental State Exam and the EXIT25 to distinguish patients who have dementia with no cortical involvement from those with cortical dementia, who receive usual care.

Patients selected for the program are treated with drugs that work on the three neurotransmitters that regulate frontal-lobe function: GABA, glutamate, and dopamine.

Starting with monotherapy, patients progress through "systematic iteration of all possible permutations of those three drugs," said Dr. Royall. After a year of evaluation, the best-performing drug is removed for clinical trials; the worst is eliminated from the program; and two new drugs are added to replace the ones removed.

Among antidepressants, sertraline has the most potent inhibition of dopamine reuptake, Dr. Royall said. Because it is predominately a serotonin reuptake inhibitor, however, higher doses are required to boost dopamine levels compared with doses used to treat depression.

Over the course of approximately six weeks, patients were titrated to a sertraline dose of 150 mg/d. Patients who did not achieve remission, defined as an EXIT25 score of less than 15, continued treatment at 200 mg/d.

The 30 patients included in the study had a mean age of 78.8. Their baseline EXIT25 score averaged 23.1, which declined to a best mean of 17.3 (irrespective of dose or treatment duration). The maximum tolerated dose of sertraline averaged 135.6 mg/d.

The most common adverse effects were sleep disturbance and motor symptoms. Two patients reported auditory hallucinations, and two had gastrointestinal effects. Side effects resolved with sertraline dose reduction or discontinuation.