A Vanderbilt University study published today in the Journal of Clinical Psychiatry may help patients prescribed higher doses of certain antidepressants feel better about attributed cardiac risks.
In high doses, the antidepressants citalopram and escitalopram have been flagged by regulators as posing risk for abnormal heart rhythms.
The new study from Vanderbilt, however, finds that these drugs in high doses don’t appear to bring any greater risk of sudden cardiac death than comparable doses of other SSRIs (selective serotonin reuptake inhibitors) used to treat mood disorders.
Citalopram is marketed under the name Celexa and escitalopram under the names Cipralex and Lexapro (other brand names also apply for both drugs).
“I think our study can provide some reassurance for people who may be benefitting from higher doses of these medications. It shows that at least there’s not a major public health threat, that if there is increased risk, it’s relatively uncommon,” said Wayne Ray, Ph.D., professor of Health Policy, who led the study.
For any given drug, the effective dose may be different for different people.
In 2011 and 2012 the Food and Drug Administration issued warnings about doses of citalopram above the normal daily dose of 40 milligrams.
The agency had found that higher doses lengthened the heart’s QT interval, which is a risk marker for potentially dangerous abnormal electrical activity in the heart. Similar warnings about high doses were issued by European regulators for both citalopram and escitalopram.
Ray’s team studied records from 54,220 Tennessee Medicaid recipients prescribed high-dose SSRIs between 1998 and 2011. In all, five SSRIs were included in the study.
To avoid counting any patient deaths less likely to be directly related to medication usage, the team took pains to exclude from the study patients with significant health problems beyond their depression.
For patients in the study, including the subset who happened to fall in the top quartile in terms of cardiovascular risk, there were no significant differences in rates of sudden cardiac death associated with high-dose citalopram, high-dose escitalopram and other high-dose SSRIs.
Two earlier large-scale retrospective studies of high-dose citalopram also found no elevated cardiac risks compared to other high-dose SSRIs.
But according to Ray those studies were seen as hampered by inadequate discrimination regarding likely causes of death.
“Citalopram was actually considered a fairly useful drug, because it’s an SSRI, it’s got good efficacy, it’s less likely than several other SSRIs to interact with other medications psychiatric patients receive, and it’s available as a generic, and thus it’s inexpensive,” Ray said.
“So it was a popular drug for treatment of patients with mood disorders. … I’m sure right now the drug guidelines writers are scratching their heads over just how to deal with this question.”
For patients who don’t respond to lower doses, according to Ray there remains a lack of studies for broadly comparing risks of high-dose SSRIs with risks of lower doses.
“In general, we could use more data on the safety of high-dose SSRIs,” he said, adding that “there’s a fair amount of data indicating that the lower doses are safe.”
Ray was joined in the study by Cecilia Chung, M.D., MPH, Kathi Hall, Katherine Murray, M.D., and C. Michael Stein, MBChB.
