by Vimal Aga, MD
Dr. Aga is a board-certified geriatric psychiatrist and an Adjunct Assistant Professor of Psychiatry and Neurology at Oregon Health Sciences University in Portland, Oregon
Agitation is a common and problematic symptom in persons with Alzheimer’s disease dementia. Citalopram is a treatment option for this problem. An important study, the CitAD trial, provided important information about this treatment. Here are a few tips about when and how to use it.
Who is more likely to benefit from citalopram?
Citalopram is best suited for treatment of agitation in the following patients:
1. Below the age of 85
2. Have mild to moderate dementia (MMSE score of 21 and above or a MoCA score of 12 and above)
3. Have lower severity of agitation.
It is not suited for the oldest-old, patients with severe cognitive impairment, or patients with severe agitation.
Citalopram is not an acute treatment for agitation, such as in an emergency room or during an acute care hospitalization, since it may take up to nine weeks for an adequate response. However, it may be started during acute hospitalization with a recommendation to continue it after discharge after explaining to the patient and family that full benefits take time to become evident.
What symptoms are more likely to improve?
The symptoms that respond the best are irritability, lability, and anxiety, and low-level delusions.
Citalopram is not established as a treatment for florid delusions or hallucinations since psychotic patients were excluded from the CitAD trial mentioned above.
Citalopram may also reduce new onset delusions, anxiety and irritability. It is not known whether this prophylactic effect would become even more significant over time, but it was already evident in the 9-week CitAD trial.
How should citalopram be dosed for this purpose?
The CitAD trial suggested that higher doses of citalopram may be needed. The benefit of lower doses of citalopram (i.e., 20 mg/day or less) are not clear from that study.
But still, I recommend that clinicians should first try lower doses of citalopram (10 to 20 mg/day).
If there is only a partial response at 10 to 20 mg/day, a higher dose of 30 mg/day may be tried. Before doing this, patients and their families should be told about the potential risks (QTc prolongation) and this discussion should be documented.
I do not recommend using citalopram at more than 30 mg/day.
How should citalopram be started and titrated?
In older patients, a starting dose of 5 mg/day is recommended.
If anxiety is present, citalopram should be titrated at no more than 5 mg per week to reduce the risk of paradoxical activation.
If the patient is on a CYP2C19 inhibitor such as omeprazole or is a known CYP2C19 poor metabolizer, greater caution is needed. In such cases, the maximum dose should be 20 mg/day.
How long should the citalopram be continued for?
The CitAD trial did not look at the duration of citalopram therapy in treatment responders. It may be best to continue the medication if it is tolerated well for as long as necessary until there is breakthrough severe agitation/aggression requiring antipsychotic medications, or the patient is end-stage.
What side effects of citalopram should we watch out for?
SSRIs, including citalopram, have a large number of side effects in the elderly, which become more problematic with longer-term use.
Patients need to be monitored for increased self-harm behaviors, seizures, falls, fractures, hyponatremia, and upper G.I. bleed (especially if they are also on an antiplatelet agent or an oral anticoagulant), and these need to be discussed with the patient and family.
QTc prolongation is discussed next.
What to do about the risk of QTc prolongation
An important issue if citalopram is used (off-label) for agitation in persons with Alzheimer’s disease is the risk of QTc prolongation.
Citalopram 30 mg/day was associated with QTc prolongation in the CitAD study (Drye et al., 2014).
A baseline ECG should be checked before starting citalopram, followed by repeat ECG’s every time the dose is increased, and especially if the total daily dose exceeds 20 mg/day.
The patient should be screened for risk factors that can prolong the QT interval. Extra caution should be exercised in patients with pre-existing heart disease, and a cardiology consult may be necessary.
Co-administering medications that prolong the QTc interval should be avoided (e.g. antipsychotics). Donepezil (Aricept®) may be particularly problematic in this regard since it not only causes QT prolongation by itself but can also result in bradycardia which can further prolong the QTc.So, extra caution and monitoring is needed in patients who are on both citalopram and donepezil.
Drye LT, Spragg D, Devanand DP, Frangakis C, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Pollock BG, Porsteinsson AP, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG; CitAD Research Group. Changes in QTc interval in the citalopram for agitation in Alzheimer’s disease (CitAD) randomized trial. PLoS One. 2014 Jun 10;9(6):e98426. PubMed PMID: 24914549; PubMed Central PMCID: PMC4051660.
Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG; CitAD Research Group. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014 Feb 19;311(7):682-91. PubMed PMID: 24549548; PubMed Central PMCID: PMC4086818.
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