Serotonergic Function and Treatment of Behavioral and Psychological Symptoms of Frontotemporal Dementia

Objectives: The purposes of this study were first, to evaluate the effectiveness of citalopram in treating behavioral disturbances in frontotemporal dementia (FTD) subjects and second, to determine whether an association exists between serotonergic function, as determined by a neuroendocrine challenge, and treatment response. Design: Single-dose citalopram (30 mg per os) challenge followed by a 6-week open-label study. Setting: Outpatients referred to memory clinics. Participants: Fifteen patients suffering from FTD with severe behavioral and psychological symptoms of dementia. Intervention: Following citalopram challenge, all patients were treated with citalopram titrated to a target dose of 40 mg once daily. Measurements: Behavioral disturbances, using the Neuropsychiatric Inventory (NPI) (primary outcome) and Frontal Behavioural Inventory (secondary outcome), were assessed. Change in prolactin concentration following citalopram challenge was used as an index of central serotonergic response. Results: Citalopram treatment was effective in treating behavioral symptoms, with significant decreases in NPI total score (F-[2,F- 28] = 6.644, p = 0.004), disinhibition (F-[2,F- 28] = 4.030, p = 0.029), irritability (F-[2,F- 28] = 7.497, p = 0.003) and depression (F-[2,F- 28] = 3.467, p = 0.045) scores over the 6 weeks. Significant improvement in Frontal Behavioural Inventory scores suggested that citalopram was also effective in the treatment of behaviors specific to FTD. A lower change score in concentration of prolactin was significantly positively correlated with greater improvement in the total NPI score from baseline to endpoint (r = 0.687, p = 0.005). A blunted response to a citalopram challenge, implying a dysfunctional serotonergic system, predicted a more positive treatment outcome. Conclusions: The results suggest that despite the endogenous serotonin deficiency of FTD, citalopram treatment may be effective in targeting the behavioral disturbances characteristic of FTD. (Am J Geriatr Psychiatry 2012; 20:789-797)