May–June 2012 Update

I n this column, I would like to make the readership aware of two updates. Two issues ago I described the drug safety communication regarding citalopram. In March of 2012, the labeling guidelines were further updated. The additional newly updated recommendations for healthcare professionals are as follow. The maximum recommended daily dose of citalopram is 20 mg for those patients with liver dysfunction, those 60 years and older, CYP-2C19 poor metabolizers, or patients concomitantly receiving cimetidine or other CYP2C19 inhibitors. These considerations are important because each of these circumstances can result in increased blood levels of citalopram, which can subsequently increase the risk of QTc interval prolongation or Torsade de Pointes. There is a special recommendation for monitoring electrocardiograms and electrolytes in those cases where citalopram may be deemed an essential component of treatment, but nonetheless the aforementioned risks may be heightened. Specifically in these cases, baseline serum potassium and magnesium measurement and periodic ongoing monitoring are essential because hypokalemia and/or hypomagnesemia can increase the risk of QTc prolongation. Discontinuation of citalopram should be undertaken when QTc intervals exceed 500 ms. Patients on citalopram who experience symptoms such as syncope, dizziness, or palpitations should contact their health care professionals.

There were two double-blind, placebo-controlled, randomized, crossover QT studies reviewed by the FDA. In one study, 119 subjects received citalopram 20, 40 and 60 mg/day, moxifloxacin 400 mg/day, and placebo. In the other study, 113 subjects received escitalopram 10, 20 and 30 mg/day, moxifloxacin 400 mg/day, and placebo. Moxifloxacin is an active control known to alter QTc intervals. In studies such as these, group changes similar to moxifloxacin imply meaningful arrhythmogenic potential. For the citalopram study, the following mean QTc changes (in ms) were noted for each group: Citalopram 20 mg=8.5, 40 mg=12.6, 60 mg=18.5, moxifloxacin=13.4. For the escitalopram study, the following mean QTc changes (in ms) were noted for each group: escitalopram 10 mg=4.5, 20 mg=6.6, 30 mg=10.75, moxifloxacin=9.0. This implies that though the antidepressant effects of the citalopram molecule seems to reside with the S-isomer, changes in QTc interval are presumably not specific to the S-isomer. Currently no changes are planned for escitalopram labeling and the maximum recommended daily dose is 20 mg.

The next update is about a novel agent that has no indication for child or adolescent psychiatry but may hold promise for patients with mild to moderate forms of Alzheimer's disease. The product is named Axona, and it is classified as a medical food that has been FDA approved as a dietary supplement. Axona is intended for the dietary management of the metabolic processes associated with Alzheimer's disease. The assumed pathway for efficacy is based on the findings that the brains of individuals with Alzheimer's disease have a decreased ability to metabolize glucose. A multicenter clinical trial, employing a double-blind, randomized, placebo-controlled design enrolled 152 patients. Those receiving Axona experienced significant improvement in the Alzheimer's Disease Assessment Scale (ADAS) cognitive measure at the 45 days' rating, while those receiving placebo had a diminution from baseline in their scores. As can be imagined, further studies are required to replicate these findings and until then there will be controversy about this agent's utility. Nonetheless, promising findings for such a serious illness are always encouraging.

We are including an updated list of conferences for your consideration.

• The 59^th Annual Meeting of the American Academy of Child and Adolescent Psychiatry will be held in San Francisco, CA from October 23–28, 2012, contact (202) 966-7300.