RECOMMENDATION: Citalopram causes dose-dependent QT interval prolongation. Citalopram should no longer be prescribed at doses greater than 40 mg per day. Citalopram should not be used in patients with congenital long QT syndrome. Patients with congestive heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia because of concomitant illness or drugs, are at higher risk of developing Torsade de Pointes.
FDA has received post-marketing reports of QT interval prolongation and Torsade de Pointes associated with Celexa and its generic equivalents. In addition, FDA has evaluated the results of a thorough QT study assessing the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. In this randomized, multi-center, double-blind, placebo-controlled, crossover study, 119 subjects received citalopram 20 mg per day (Day 9), citalopram 60 mg per day (Day 22), and placebo. The overall summary of findings is presented in Table 1
Table 1: Increase in the Corrected QT Interval for Citalopram (FDA Analysis)
| Citalopram Dose | Increase in QT Interval (ms) | 90% Confidence Interval (ms) |
|---|---|---|
| 20 mg/day | 8.5 | (6.2, 10.8) |
| 60 mg/day | 18.5 | (16.0, 21.0) |
| 40 mg/day | 12.6* | (10.9, 14.3)* |
*Estimate based on the relationship between citalopram blood concentration and QT interval.
Compared to placebo, maximum mean prolongations in the individually corrected QT intervals were 8.5 and 18.5 milliseconds (ms) for 20 mg and 60 mg citalopram, respectively. For 40 mg citalopram, prolongation of the corrected QT interval was estimated to be 12.6 ms.
As a result of this thorough QT study, FDA has determined that citalopram causes dose-dependent QT interval prolongation and should no longer be used at doses above 40 mg per day. Important safety information about the potential for QT interval prolongation and Torsade de Pointes with drug dosage and usage recommendations are being added to the package inserts of Celexa and its generic equivalents.
What does this mean for our patients with depression and anxiety that have felt a benefit from the increased dose of citalopram 60mg?
Consider the following:
1. Discuss with the patient the US FDA recommendations and possible increase risk of QT prolongation.
2. Suggest monitor ECG, serum K+ and Mg+ (regularly if maintaining dose of 60mg)
3. If tapering to citalopram 40mg, follow up with the patient accordingly to ensure no relapse (e.g., within the month)
4. If relapse occurs, consider switching to sertraline (max dose = 200mg/d) or augmenting with bupropion (depending on the diagnosis of treatment) {e.g., if depression+anxiety, consider sertraline. If major depressive disorder only, consider adding bupropion (bupropion may increase anxiety)}
If you have any other suggestions or comments, please feel free to share on this blog!
References:
1. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm
2. http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm
