Frontotemporal Dementia: Treatment Response to Serotonin Selective Reuptake Inhibitors

Background: Patients with frontotemporal dementia (FTD) present initially with primarily behavioral rather than cognitive symptoms. Decreased serotonin receptor binding has been reported in the frontal lobes, temporal lobes, and hypothalamus in autopsy-proven FTD cases. This study tests the hypothesis that many of the behavioral symptoms of FTD (including disinhibition, depressive symptoms, carbohydrate craving, and compulsions) will respond to serotonin selective reuptake inhibitors (SSRIs).

Method: Eleven subjects meeting the Lund Manchester clinical, neuropsychological, and neuroimaging criteria for FTD were treated with SSRIs (fluoxetine, sertraline, or paroxetine). After 3 months, treatment responses for disinhibition, depressive symptoms, carbohydrate craving, and compulsions were evaluated prospectively without placebo control.

Results: After treatment, disinhibition, depressive symptoms, carbohydrate craving, and compulsions all showed improvement in at least half the subjects in which they had been present. One subject stopped sertraline treatment because of diarrhea, while another stopped paroxetine treatment due to increased anxiety. The presence of individual behavioral symptoms and also the response of each symptom to SSRIs were unrelated to cognitive impairment as measured by baseline MiniMental Status Examination (.07אpא1.00).

Conclusion: The behavioral symptoms of FTD may improve after treatment with SSRIs. Future neurochemical studies and controlled pharmacologic trials may improve available treatments.