Citalopram for agitation in Alzheimer's disease: Design and methods

Abstract

Background Agitation is one of the most common neuropsychiatric symptoms of Alzheimer’s disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer’s disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms. Methods CitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study has eight recruiting clinical centers, a chair’s office and a coordinating center located in university settings in the United States and Canada. 200 people having probable Alzheimer’s disease with clinically significant agitation and without major depression are being recruited. Patients are randomized to receive citalopram (target dose of 30 mg/day) or matching placebo. Caregivers of patients in both treatment groups receive a structured psychosocial therapy. Agitation will be compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change which are the primary outcomes. Functional performance, cognition, caregiver distress and rates of adverse and serious adverse events will also be measured. Conclusion The authors believe the design elements in CitAD are important features to be included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in Alzheimer’s disease.

O5‐06‐06: Changes in QTC Interval in the Citalopram for Agitation in Alzheimer's Disease (Citad) Randomized Trial

“…CitAD participants had probable Alzheimer's disease as defined by NINCDS-ADRDA [17] criteria, Mini-Mental State Examination (MMSE) [18] scores of 5-28 inclusive, and clinically significant agitation. The detailed list of eligibility criteria for CitAD has been published previously [19]. The protocol for CitAD and supporting CON-SORT checklist are available as supporting information; see Protocol S1 and Checklist S1.…”

“…The CitAD sample size requirements were based on the primary outcomes and have been published [19,20]. Enrollments following the introduction of the new ECG monitoring procedures in 2011 continued to be balanced between the citalopram and placebo groups.…”

Advancements in the treatment of agitation in Alzheimer’s disease

“…Patients with depressive or psychotic symptoms requiring treatment were excluded. The CitAD study also measured safety and tolerability of the active treatment as well as its effect on caregiver distress [14]. The study found statistically significant and clinically meaningful reduction in agitation in the citalopram group over placebo on both primary outcome measures: The Neurobehavioral Rating Scale, agitation subscale estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 points (95% CI: -1.80 to -0.06; p = 0.04).…”

“…For decades, antipsychotics have been the pragmatic mainstay of treatment despite their limited efficacy, and history of adverse events outweighing potential benefits including FDA black box warnings [13]. Risks surrounding antipsychotic use, both conventional and atypical, range from weight gain, falls and drowsiness to increased cerebrovascular events and mortality rate in elderly individuals [14]. Major efforts are underway in the USA and worldwide to limit the use of antipsychotics in patients with dementia due to these safety concerns.…”

Designing a Trial to Evaluate Potential Treatments for Apathy in Dementia: The Apathy in Dementia Methylphenidate Trial (ADMET)

“…ADMET will also use a clinician rating of target behavior change similar to the approach used in the Depression in Alzheimer’s Disease Study-2 (DIADS-2) (26) and the Citalopram for Agitation in Alzheimer’s Disease (CitAD) trial (27). We modified the ADCS-CGIC by adding apathy-specific interview questions and probes based on Marin’s core features of apathy: lack of initiative, lack of interest and emotional blunting (16).…”