The Citalopram for Agitation in Alzheimer Disease Study (CitAD) randomized 186 AD patients with clinically significant agitation to psychosocial intervention with or without citalopram 30 mg/day for nine weeks (Porsteinsson et al. JAMA 2014;311:682-691). The dose of citalopram was titrated from 10 mg/day to the planned dose of 30 mg/day over three weeks.
Subjects receiving citalopram had significant improvement in Neurobehavioral Rating Scale-agitation subscale (NBRS-A) scores (treatment effect -0.93). On the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), 40% of patients showed moderate or marked improvement from baseline with citalopram versus 26% on placebo. There were also improvements on the Cohen-Mansfield Agitation Inventory (CMAI), total Neuropsychiatric Inventory (NPI) scores, and on caregiver distress scores. Improvements were not seen on the NPI agitation subscale, activities of daily living, or in the use of rescue lorazepam.
However, citalopram was associated with significant worsening of cognitive function. In addition, the SSRI was significantly associated with QT interval prolongation (18.1 msec). QT prolongation is a known dose-dependent effect of citalopram that has been associated with torsades de pointes, ventricular tachycardia and sudden death. Doses above 20 mg/day are not recommended in patients aged 60 years or older.
The authors concluded that while citalopram does appear to be effective for agitation, the use of the 30-mg dose will be limited due to the problem of adverse effects.
Dr. Catherine Brodeur: Given the multiple side effects and black box warnings associated with antipsychotic drugs, other types of drugs with a lower risk profile would be welcome in the treatment of BPSD (behavioural and psychological symptoms of dementia), especially agitation. This study was done prior to the FDA and Health Canada warnings regarding the risk of increased QTc and torsades de pointes with citalopram. We now know that, as per Health Canada, a dosage of more than 20 mg daily is to be avoided in people over 65 years old (60 years old as per FDA). It would be interesting to repeat this study with citalopram 20 mg.