According to the U.S. Food and Drug Administration (FDA), the antidepressant Celexa (citalopram hydrobromide, which is also available as a generic) should no longer be used at doses greater than 40 mg per day.
The FDA issued the warning to health care professionals because researchers found that Celexa can cause abnormal changes in the electrical activity of the heart when taken at higher doses — leading to possible damage of the heart. Previous scientific studies of Celexa did not show a benefit in the treatment of depression at doses higher than 40 mg per day.
Celexa (citalopram hydrobromide) is a type of antidepressant called selective serotonin reuptake inhibitors (SSRIs) commonly prescribed by doctors and psychiatrists for clinical depression. While scientists don’t know exactly how antidepressants work to reduce depression, it is thought to work by increasing the amount of the chemical neurotransmitter serotonin in the brain. In the U.S., it is currently available in 10 mg, 20 mg, and 40 mg tablets, and is also available as an oral solution (10 mg/5 mL).
Previously, the drug label on Celexa stated that certain patients may require a dose of 60 mg per day. It is thought that doctors have issued many prescriptions for Celexa at this higher dose.
The new warning comes as FDA researchers reviewed previous research and found a direct correlation between the higher the dose of Celexa, and greater risk to the heart.
Changes in the electrical activity of the heart (prolongation of the QT interval of the electrocardiogram [ECG]) can lead to an abnormal heart rhythm, which can be fatal.
Patients at particular risk for developing prolongation of the QT interval include those with underlying heart conditions and those who are predisposed to low levels of potassium and magnesium in the blood.
The citalopram drug label has been revised to include the new drug dosage and usage recommendations, as well as information about the potential for QT interval prolongation and Torsade de Pointes. (See Additional Information for Healthcare Professionals)
If you’re on Celexa now, it’s important for you to be aware of the following:
The FDA told health care professionals who prescribe Celexa that it causes dose-dependent QT interval prolongation. They warned that the drug should no longer be prescribed at doses greater than 40 mg per day, nor should it 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.
The FDA also noted that hypokalemia and hypomagnesemia should be corrected before administering citalopram. Electrolytes should be monitored as clinically indicated. They told healthcare professionals to consider more frequent electrocardiogram (ECG) monitoring in patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval.
The 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
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.
Source: U.S. Food and Drug Administration