A critical evaluation of the cardiac toxicity of citalopram: part 2

In August 2011, the U.S. Food and Drug Administration issued a drug safety communication that the antidepressant drug citalopram (Celexa®) should not be used at dosages greater than 40 mg per day (or greater than 20 mg per day for patients 60 and older) because higher doses have been associated with abnormal heart rhythms. Clinical studies using citalopram in patients with cardiac disease and in older patients do not confirm such a risk. The major metabolite of citalopram is demethylcitalopram, which is subsequently metabolized to the minor metabolite didemethylcitalopram (DDCT). High DDCT concentrations have been associated with QT interval prolongation in beagle dogs. Therapeutic drug monitoring study data suggest that routine or even high oral doses of citalopram are unlikely to result in cardiotoxic concentrations of the DDCT metabolite. Based on evidence taken from a wide variety of studies, the citalopram dose limitations described in the safety announcement do not have strong clinical justification.