Sedation mediates part of Citalopram's effect on agitation in Alzheimer's disease

Abstract

Background We found a benefit of citalopram for agitation in the Citalopram for Agitation in Alzheimer’s Disease study (CitAD), and wondered if this was mediated by a sedative effect. CitAD was a randomized, placebo-controlled, double-blind, parallel group trial conducted at 8 academic centers in the United States and Canada from August 2009 to January 2013. One hundred sixty-two participants with probable Alzheimer’s disease (AD) and clinically significant agitation were analyzed in this study. Participants received a psychosocial intervention and were randomized to receive either citalopram or placebo (approximately half assigned to each group). Participants were rated on the Neurobehavioral Rating Scale Agitation subscale and measures of sedation (i.e., fatigue and somnolence). Methods Using the MacArthur Foundation procedures for documenting a mediator effect, we performed a secondary analysis examining whether sedation mediates the effect of treatment on agitation outcome. Results We found a statistically significant mediating effect of sedation on agitation outcomes, but the magnitude of the effect was small, only explaining 11% of the variance in agitation, with a significant, but modest effect size of 0.16 (95% CI: 0.08 to 0.22). Conclusions The benefit of citalopram was partly due to sedation but largely due to other mechanisms of action.

A review of citalopram dose restrictions in the treatment of neuropsychiatric disorders in older adults

“…Treatment options for behavioral and psychological symptoms of dementia (BPSD; eg antipsychotics) have modest evidence for efficacy and have significant limitations, including the propensity to increase metabolic disorders, falls, drug interactions, and mortality 25-28. Citalopram has been studied in several capacities29-35 regarding its potential to manage multiple manifestations of BPSD (Table 2). The exact mechanism of how citalopram is efficacious for BPSD is largely unknown; however, it is likely not owed completely to sedation 29…”

“…Citalopram has been studied in several capacities29-35 regarding its potential to manage multiple manifestations of BPSD (Table 2). The exact mechanism of how citalopram is efficacious for BPSD is largely unknown; however, it is likely not owed completely to sedation 29…”

The Development of Pharmacological Therapies for Alzheimer’s Disease

“…The authors further suggested that those with moderate agitation but less cognitive impairment were more likely to obtain benefits from citalopram, whereas more severe cases, especially dementia patients, could be at higher risk of sleep disturbances [ 103 ]. In a secondary analysis, the benefits of citalopram were only partially (11%) due to sedation, and largely due to unknown mechanisms [ 104 ].…”

Remission in visual hallucinatory experiences after citalopram treatment in a patient with dementia

“…3,4 Citalopram was shown to be beneficial for agitation, aggression, irritability and other neuropsychiatric symptoms in Alzheimer's disease. 5 Siddique et al evaluated the effectiveness of citalopram in Alzheimer's disease by using a neuropsychiatric inventory in their study named Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease. Their retrospective analyses showed that it is beneficial for the treatment of those with agitation, delusion, hallucination, depression, aggression, euphoria, disinhibition, irritability, apathy, abnormal motor behavior, sleep and appetite.…”