FDA: High-Dose Citalopram Tied to Heart Risks

The antidepressant citalopram should not be used at doses greater than 40 mg per day because such doses can lead to prolongation of the QT interval, the Food and Drug Administration announced Aug. 24 in a drug safety communication. Further, the drug should not be prescribed to patients with congenital long QT syndrome, and extra precautions should be taken for patients with other underlying heart conditions, the agency said.

Studies do not show a benefit in the treatment of depression at doses of the selective serotonin reuptake inhibitor higher than 40 mg/day. Previously, the citalopram (Celexa) label stated that some patients might require a dose of 60 mg/day.

The agency’s dosage recommendation is based on postmarketing reports of QT prolongation associated with citalopram and results of a randomized, double-blind, placebo-controlled crossover study evaluating the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. The latter study showed that, compared with placebo, the maximum mean prolongations in the individually corrected QT intervals for patients randomized to 20-mg and 60-mg doses of citalopram, respectively, were 8.5 msec and 18.0 msec. The prolongation of the corrected QT interval was estimated to be 12.6 msec, based on the relationship between serum citalopram concentration and QT interval, the FDA statement said.

Because such dose-dependent changes in the electrical activity of the heart can lead to abnormal heart rhythms, including the potentially fatal torsades de pointes, and in the absence of evidence demonstrating that citalopram at doses higher than 40 mg/day is beneficial in the treatment of depression, the FDA determined that citalopram should no longer be used at doses above 40 mg/day and that it should never be used in patients with congenital long QT syndrome.

Also, because individuals with underlying heart conditions, such as heart failure or bradyarrhythmias and those predisposed to insufficient serum potassium and magnesium because of comorbid illness or other drugs are at particular risk, the FDA has made the following safety recommendations:

• Correct hypokalemia and hypomagnesemia before administering citalopram and monitor electrolytes as clinically indicated.

• Consider more frequent electrocardiogram monitoring for patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval.

• The maximum recommended dose for patients with hepatic impairment, who are older than 60 years, who are CYP 2C19 poor metabolizers, or who are taking cimetidine is 20 mg/day because each of these factors can increase blood levels of citalopram, thus increasing the risk of QT interval prolongation and torsades de points.

• Advise patients to contact a health care professional if they experience signs or symptoms of an abnormal heart rate or rhythm while taking citalopram.

The citalopram drug label has been revised to include the new drug dosage and usage recommendations, and the revised package insert will include information about the potential for QT interval prolongation and torsades de pointes.

The antidepressant citalopram should not be used at doses greater than 40 mg per day because such doses can lead to prolongation of the QT interval, the Food and Drug Administration announced Aug. 24 in a drug safety communication. Further, the drug should not be prescribed to patients with congenital long QT syndrome, and extra precautions should be taken for patients with other underlying heart conditions, the agency said.

Studies do not show a benefit in the treatment of depression at doses of the selective serotonin reuptake inhibitor higher than 40 mg/day. Previously, the citalopram (Celexa) label stated that some patients might require a dose of 60 mg/day.

The agency’s dosage recommendation is based on postmarketing reports of QT prolongation associated with citalopram and results of a randomized, double-blind, placebo-controlled crossover study evaluating the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. The latter study showed that, compared with placebo, the maximum mean prolongations in the individually corrected QT intervals for patients randomized to 20-mg and 60-mg doses of citalopram, respectively, were 8.5 msec and 18.0 msec. The prolongation of the corrected QT interval was estimated to be 12.6 msec, based on the relationship between serum citalopram concentration and QT interval, the FDA statement said.

Because such dose-dependent changes in the electrical activity of the heart can lead to abnormal heart rhythms, including the potentially fatal torsades de pointes, and in the absence of evidence demonstrating that citalopram at doses higher than 40 mg/day is beneficial in the treatment of depression, the FDA determined that citalopram should no longer be used at doses above 40 mg/day and that it should never be used in patients with congenital long QT syndrome.

Also, because individuals with underlying heart conditions, such as heart failure or bradyarrhythmias and those predisposed to insufficient serum potassium and magnesium because of comorbid illness or other drugs are at particular risk, the FDA has made the following safety recommendations:

• Correct hypokalemia and hypomagnesemia before administering citalopram and monitor electrolytes as clinically indicated.

• Consider more frequent electrocardiogram monitoring for patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval.

• The maximum recommended dose for patients with hepatic impairment, who are older than 60 years, who are CYP 2C19 poor metabolizers, or who are taking cimetidine is 20 mg/day because each of these factors can increase blood levels of citalopram, thus increasing the risk of QT interval prolongation and torsades de points.

• Advise patients to contact a health care professional if they experience signs or symptoms of an abnormal heart rate or rhythm while taking citalopram.

The citalopram drug label has been revised to include the new drug dosage and usage recommendations, and the revised package insert will include information about the potential for QT interval prolongation and torsades de pointes.

The antidepressant citalopram should not be used at doses greater than 40 mg per day because such doses can lead to prolongation of the QT interval, the Food and Drug Administration announced Aug. 24 in a drug safety communication. Further, the drug should not be prescribed to patients with congenital long QT syndrome, and extra precautions should be taken for patients with other underlying heart conditions, the agency said.

Studies do not show a benefit in the treatment of depression at doses of the selective serotonin reuptake inhibitor higher than 40 mg/day. Previously, the citalopram (Celexa) label stated that some patients might require a dose of 60 mg/day.

The agency’s dosage recommendation is based on postmarketing reports of QT prolongation associated with citalopram and results of a randomized, double-blind, placebo-controlled crossover study evaluating the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. The latter study showed that, compared with placebo, the maximum mean prolongations in the individually corrected QT intervals for patients randomized to 20-mg and 60-mg doses of citalopram, respectively, were 8.5 msec and 18.0 msec. The prolongation of the corrected QT interval was estimated to be 12.6 msec, based on the relationship between serum citalopram concentration and QT interval, the FDA statement said.

Because such dose-dependent changes in the electrical activity of the heart can lead to abnormal heart rhythms, including the potentially fatal torsades de pointes, and in the absence of evidence demonstrating that citalopram at doses higher than 40 mg/day is beneficial in the treatment of depression, the FDA determined that citalopram should no longer be used at doses above 40 mg/day and that it should never be used in patients with congenital long QT syndrome.

Also, because individuals with underlying heart conditions, such as heart failure or bradyarrhythmias and those predisposed to insufficient serum potassium and magnesium because of comorbid illness or other drugs are at particular risk, the FDA has made the following safety recommendations:

• Correct hypokalemia and hypomagnesemia before administering citalopram and monitor electrolytes as clinically indicated.

• Consider more frequent electrocardiogram monitoring for patients with congestive heart failure, bradyarrhythmias, or patients on concomitant medications that prolong the QT interval.

• The maximum recommended dose for patients with hepatic impairment, who are older than 60 years, who are CYP 2C19 poor metabolizers, or who are taking cimetidine is 20 mg/day because each of these factors can increase blood levels of citalopram, thus increasing the risk of QT interval prolongation and torsades de points.

• Advise patients to contact a health care professional if they experience signs or symptoms of an abnormal heart rate or rhythm while taking citalopram.

The citalopram drug label has been revised to include the new drug dosage and usage recommendations, and the revised package insert will include information about the potential for QT interval prolongation and torsades de pointes.