Effect of memantine combined with citalopram on cognition of BPSD and moderate Alzheimer's disease: A clinical trial

Abstract

Among Alzheimer's disease (AD) patients, it is very common to develop behavioral and psychological symptoms of dementia (BPSD), which has a close relation to the excess morbidity and mortality, greater healthcare use, earlier institutionalization, and caregiver burden. With evaluation of AD patients, the present study mainly aims to investigate whether citalopram would be efficient for BPSD, and examines citalopram's effects on cognitive function, caregiver distress, safety and tolerability. Eighty patients diagnosed with moderate AD and clinically significant BPSD from April 2015 to January 2016 were enrolled in this study. Patients randomly received memantine plus either citalopram (n=40, study group) or placebo (n=40, control group) in a 12-week period. The target dose of memantine was 20 mg/day. The dose of citalopram was 10 mg/day in the beginning with planned titration to 30 mg/day over 2 weeks on the basis of response and tolerability. Blood routine, urine routine, biochemical tests, electrocardiogram and electroencephalogram were carried out for each patient every month routinely to check the change induced by using medication. Treatment Emergent Symptom Scale (TESS) was used to measure untoward effects every 2 weeks. All of the agitation/aggression, irritability/lability, night-time behavioral disturbances, caregiver distress and Neuropsychiatric Inventory (NPI) total scores after treatment were found to be dramatically lower than those before treatment in both groups. Apathy, dysphoria and anxiety received lower scores in participants who received memantine combined with citalopram, compared to those before treatment. QTc interval prolongation was observed in 2 patients who were treated with 30 mg/day citalopramin. In conclusion, memantine combined with citalopram can more effectively improve the cognitive function, and reduce behavioral and psychological symptoms in patients with moderate AD. Cardiac adverse effects of citalopram are not common when the dose is <30 mg/day, which does not limit its practical application. Thus, citalopram has shown potential efficacy in adjunctive therapy of AD patients with BPSD.

Keywords: Alzheimer's disease; BPSD; caregiver distress; citalopram; cognitive; memantine; randomized trial.