Hospitalizations Among Veterans Rise After Citalopram Prescriptions Are Reduced

The 2011 warning of the Food and Drug Administration (FDA) against prescribing doses of citalopram above 40 mg/day was back in the news last month after a report published in AJP in Advance concluded that all-cause hospitalizations and deaths among veterans rose significantly following reductions in prescribed doses of the medication.

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The FDA’s 2011 warning came after evidence suggested that doses of citalopram exceeding 40 mg/day were associated with QT prolongation.

The move was intended to reduce the incidence of fatalities and health problems due to QT interval prolongation, but study authors David Rector, Ph.D., Pharm.D., of the University of Minnesota and colleagues observed an uptick in suicidal ideation and hospitalization for worsening depression after citalopram doses were reduced.

Rector and colleagues analyzed data contained in the Veterans Health Administration’s national electronic medical records database to determine if unintended increases in suicide and hospitalization due to worsening depression were offsetting the intended benefits of limiting citalopram.

They identified 265,795 veterans who filled at least one outpatient citalopram prescription in the three months before August 2011. At the time the warning was issued, 35,848 veterans had active citalopram prescriptions for an average dosage of 64 mg/day. Within 180 days after the safety communication was issued, 60 percent had filled prescriptions for 40 mg/day or less.

The researchers used statistical analysis to compare hospitalizations and mortality after citalopram doses were or were not reduced to 40 mg/day or less. They found the unadjusted incidence of all-cause hospitalizations or deaths was more than 2.5 times higher after citalopram dosages were reduced to 40 mg/day or less. Hospitalizations for depression, diagnoses of self-injury, or death were also higher after citalopram dosages were reduced. At the same time, there was no noticeable reduction in hospitalizations for cardiac arrhythmias, according to the researchers.

“In the present study, deaths that were directly or possibly indirectly related to worsening mental health may have offset deaths from cardiac arrhythmias incurred by a continuance of higher prescription dosages,” the researchers wrote. “The safety warning may have prompted electrocardiograms that led to dosage reductions that prevented some hospitalizations for cardiac arrhythmias and deaths. However, the net effect of the large number of citalopram dosage reductions that occurred shortly after the safety communications were issued appeared to manifest as an increase in hospitalizations for mental health disorders.”

The FDA stood by its recommendation to limit dosage of citalopram to 40 mg/day after a commentary on a similar study was published in the American Journal of Psychiatry in January 2014.

In response to a request for comment on the paper by Rector and colleagues, an FDA spokesperson told Psychiatric News, “The FDA does not typically comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

The study was funded by a VA Health Services Research and Development grant. ■