The August 2011 FDA communication stated that doses of citalopram above 40 mg/day may be associated with risk for arrhythmia related to QT prolongation. But today’s AJP study appears to indicate serious unintended consequences in the form of increased hospitalization for mental disorders.
“Rapidly reducing dosages from [greater than] 60 mg/day to 40 mg/day [or less] may have precipitated worsening symptoms of depression, PTSD, and other mental health disorders,” wrote David Rector, Ph.D., Pharm.D., of the University of Minnesota, and colleagues.
The researchers searched the VA’s national electronic medical records database and found 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 64 mg/day, on average. Within 180 days after the safety communication was issued, 60% 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.”
In response to a request for comment by Psychiatric News, an FDA spokesperson replied, “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.”
For previous coverage of the FDA’s decision to warn health care providers against prescribing citalopram at doses exceeding 40 mg/day, see the Psychiatric News article “FDA Responds to AJP Manuscript on Citalopram Safety.”