Blog | Friday, February 21, 2014

QD: News Every Day--Medication to treat agitation for Alzheimer's disease may have cardiologic consequences


Citalopram at 30 mg per day was associated with a reduction in agitation in patients with Alzheimer’s disease, but patients experienced mild cognitive and cardiac effects that might limit its use, a study found.

Researchers randomized 186 patients with probable Alzheimer’s disease without major depression and clinically significant agitation from 8 academic centers in the United States and Canada to receive citalopram (n=94) or placebo (n=92) for 9 weeks. Interventional dosage began at 10 mg per day titrated to 30 mg per day over 3 weeks based on response and tolerability. Both groups received psychological counseling and assistance.

Results appeared in the Feb. 19 issue of JAMA.

The estimated treatment difference at week 9 (citalopram minus placebo) on the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) was −0.93 (95% CI, −1.80 to −0.06), P=0.04. Results from the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients. The odds ratio (OR) of being at or better than a given CGIC category was 2.13 (95% CI, 1.23-3.69), P=0.01. Participants who received citalopram showed significant improvement on the Cohen-Mansfield Agitation Inventory (CMAI), total Neuropsychiatric Inventory (NPI) and caregiver distress scores. But, they did not improve when assessed by the NPI agitation subscale, activities of daily living or in less use of rescue lorazepam.

Worsening of cognition (−1.05 points; 95% CI, −1.97 to −0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P=0.01) were seen in the citalopram group, leading researchers to conclude that citalopram cannot be generally recommended as an alternative treatment option at 30 mg per day.

Researchers wrote, “An assessment of individual patient circumstances, including symptom severity, value of improvement, cognitive function and change, cardiac conduction, vulnerability to adverse effects, and effectiveness of behavioral interventions can help guide appropriate medication use in patients with marked agitation or aggression.”

An editorial noted that clinicians should continue to emphasize nonpharmacological strategies and cautiously use medications.

“In addition to educating caregivers and family members about the potential risks and benefits of particular medications, physicians should carefully document their treatment plans and aim for short-term treatment to minimize the possible added risks of long-term use,” the editorial stated. “As demonstrated by the results of this study of citalopram, when behavioral interventions fail to improve agitation, multiple factors need consideration for selecting the best medication for an individual patient, including cardiac safety issues and evidence of efficacy from randomized controlled trials. Until more definitive treatments are available, the careful selection and monitoring of pharmacologic agents may help optimize the level of functioning and quality of life for some patients with dementia.”