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Higher-Dose Citalopram and the FDA Warnings: Not Much to Worry About?

Summary and Comment |
May 20, 2013

Higher-Dose Citalopram and the FDA Warnings: Not Much to Worry About?

  1. Joel Yager, MD

In a large study, no increased cardiac risks were associated with citalopram doses higher than 40 mg/day.

  1. Joel Yager, MD

FDA alerts issued in 2011 and 2012 (http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm) warned that patients receiving more than 40 mg/day of citalopram were at increased risk of dose-dependent QT interval prolongation. The alerts advised that citalopram not be prescribed at doses higher than 40 mg/day or, for patients over 60, higher than 20 mg/day, nor be used in patients with congenital long QT syndrome. Further, the alert noted that risk for the potentially fatal torsade de pointes was increased in patients with congestive heart failure and other specific cardiac-related problems.

Using data from a national Veterans Affairs (VA) depression registry and a national mortality index, investigators with VA funding examined records from 2004–2009 of 618,450 individuals receiving citalopram prescriptions and 365,898 receiving prescriptions for sertraline — another selective serotonin reuptake inhibitor, but not subject to the FDA cardiac warnings.

Overall, 1.1% of patients receiving citalopram or sertraline experienced ventricular arrhythmias. Cardiac deaths occurred in 3.3% of citalopram recipients and 4.0% of sertraline recipients. In an analysis controlling for some demographic and clinical covariates, daily citalopram above 40 mg/day, compared with doses of less than 20 mg/day, were associated with lower risks of ventricular arrhythmias; no elevated cardiac mortality risks were seen. Sertraline analyses yielded similar results.

Comment

Several potential confounders may not have been fully controlled: Patients receiving lower citalopram doses tended to be older and had more medical comorbidities and a higher death rate. The FDA's initial warnings on citalopram-linked torsade de pointes were based largely on case reports. Thus, the findings from this impressively large data set should reassure patients whose illnesses require higher citalopram doses. The authors prudently invite the FDA to reexamine its warnings. Until then, clinicians and patients must still contend with current FDA guidance and should carefully weigh that guidance against potential treatment benefits on a case-by-case basis.

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