High-Doses of Antidepressants Less Risky on Heart Than Initially Thought

High doses of the antidepressants citalopram (Celexa) and escitalopram (Cipralex, Lexapro) do not appear to carry greater risk of sudden cardiac death than comparable doses of other selective serotonin reuptake inhibitors (SSRIs), according to a new study in the Journal of Clinical Psychiatry. Previous studies of high doses of citalopram (>40 mg) and escitalopram (>20 mg) prompted the FDA to issue warnings about doses of citalopram above the normal daily dose of 40 mg because the agency said these doses pose risks for abnormal heart rhythms by prolonging the QT interval. The European drug regulatory agency also issued similar warnings for both citalopram and escitalopram.

Vanderbilt University professor Wayne A. Ray, PhD, professor of Health Policy, and colleagues, followed 54,220 persons 30 to 74 years of age who were participants in the Tennessee Medicaid retrospective cohort study and were prescribed 5 different high-dose SSRIs from 1998 through 2011. All were without cancer or other life-threatening illness, with a mean age of 46 years (76% female). Demographic characteristics and comorbidity for individual SSRIs were comparable. The researchers analyzed out-of-hospital sudden, unexpected deaths as well as sudden cardiac deaths because they were more specific indicators of arrhythmia-related deaths, which typically occur outside the hospital.

The researchers report that patients in the study had no significant differences in rates of sudden cardiac death associated with high-dose citalopram, high-dose escitalopram, and other high-dose SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) were 0.84 (95% confidence interval [CI], 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (65 years of age or higher with upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point.

“I think our study can provide some reassurance for people who may be benefiting from higher doses of these medications,” Ray said in a statement. “It shows that at least there’s not a major public health threat, and that if there is increased risk, it’s relatively uncommon.”

The investigators noted that 2 earlier large-scale retrospective studies of high-dose citalopram also found no elevated cardiac risks compared with other high-dose SSRIs, but these studies had problems regarding likely cause of death.

Citalopram has been a popular drug for patients with mood disorders because it’s effective, less likely than other SSRIs to interact with other medications psychiatric patients receive, and is a generic and thus inexpensive, Ray said. For patients who don’t respond to lower doses there remains a lack of studies for broadly comparing risks of high-dose SSRIs with risks of lower doses, and more data are needed on the safety of high-dose SSRIs.

“In general, we could use more data on the safety of high-dose SSRIs,” Ray said, adding that “there’s a fair amount of data indicating that the lower doses are safe.”