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

Abstract

Introduction Neuropsychiatric disorders affect millions of older adults. Despite this, there are relatively few older adults included in clinical trials evaluating treatments for psychiatric disorders. Citalopram has been evaluated in older adults with neuropsychiatric disorders and has largely been found beneficial, making the 2011 US Food and Drug Administration (FDA) safety advisory on citalopram extremely impactful. Methods A literature search was completed using the PubMed database. Results were limited to clinical trials conducted in older adults that were published in English. Results Review of the literature confirms the efficacy of citalopram in depression, anxiety, depression associated with Parkinson disease, and behavioral and psychological symptoms of dementia. Additionally, no adverse cardiac outcomes have been described related to citalopram. Discussion The FDA's evidence for applying this safety advisory to citalopram is minimal and largely based on surrogate markers, such as the QTc interval rather than clinical and safety outcomes. Citalopram is known to increase the QTc, but this increase has not been linked to adverse cardiac outcomes. The evidence for efficacy and against adverse outcomes suggests that a reevaluation of the dosing restrictions in older adults with neuropsychiatric disorders is needed.

Management of Dementia-Related Psychosis, Agitation and Aggression: A Review of the Pharmacology and Clinical Effects of Potential Drug Candidates

“…In fact, in August 2011, the FDA announced a safety warning recommending to limit the maximum dose of citalopram to 20 mg/day in elderly patients aged > 60 years because of the possible occurrence of QT prolongation [104]. Therefore, it has been suggested that lower doses (< 30 mg/day) of citalopram [103] or alternatively other non-cardiotoxic antidepressants should be evaluated in clinical trials [105].…”

Behavioral Variant Frontotemporal Dementia: Diagnosis and Treatment Interventions

“…Of note, for patients older than 60 years, there exists an FDA warning of dose-dependent QTc increase with the usage of citalopram at doses greater than 20 mg. QTc data in the FDA's original drug safety warning showed an approximate 4 ms difference between 20 mg/day and 40 mg/ day [37]. But the clinical implication of this warning is unclear [38]. Studies of sertraline (50-100 mg) use in treating FTD symptoms are limited to mainly observational studies [39].…”

A comparative analysis of selective serotonin reuptake inhibitors and fall risk in older adults

“…We found that a high dose of citalopram/escitalopram was associated with a higher risk of recurrent falls compared to high dose sertraline, however, this relationship was not observed at low or medium doses. Guidance from the Food and Drug Administration (FDA) restricts the use of high dose citalopram (defined as over 20 mg daily) in adults over the age of 60 due to a potential risk of abnormal heart rhythms 23,24 . These FDA restrictions were issued in 2012 during the time our second MCBS cohort was surveyed (2012–2013).…”

“…High‐dose citalopram could be associated with abnormal heart rhythms, such as QT prolongation, which often result in dizziness, fainting spells, and an erratic heartbeat, all risk factors for falls. While citalopram has been implicated in QT interval prolongation on electrocardiogram (ECG), 25 there is limited evidence linking it to adverse cardiac outcomes 23 . However, falls and QT prolongation have shared risk factors including female sex, advancing age, and comorbidities such as stroke and diabetes 25 .…”

“…Guidance from the Food and Drug Administration (FDA) restricts the use of high dose citalopram (defined as over 20 mg daily) in adults over the age of 60 due to a potential risk of abnormal heart rhythms. 23,24 These FDA restrictions were issued in 2012 during the time our second MCBS cohort was surveyed (2012-2013). While these restrictions were issued in 2012, a similar proportion of participants in our study used high dose citalopram (>20 mg/ day) in 2016 compared to before and shortly after the FDA restrictions (2010 and 2012) which may suggest that these restrictions are not being implemented.…”