“Our study in nonelderly adults with depression did not identify a single predominant cause of death. However, this may be a result of both the relatively small number of deaths in our study as well as of the well-recognized concerns regarding the accuracy of cause-of-death attribution in death certificates,” Gerhard said.
“As with the potential causes of death, the pathophysiological pathways involved are not well understood but could, among others, involve adverse metabolic effects, including weight gain, diabetes, dyslipidemia, QT prolongation, sedation, and falls ― all of which have been associated with at least some of the newer antipsychotics,” he added.
The researchers state that atypical antipsychotics should only be considered “after non-response to evidence-based treatment options that are less risky.”
Another Red Flag
Commenting for Medscape Medical News, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Northwell Health’s Staten Island University Hospital in New York City, said this is a “valid contribution” and represents the second large study that “raises the same concern.”
“We’ve been probably underestimating the risk in administering them, and that’s something people really need to know, because if you’re prescribing it for someone with mild to moderate depression, it may be helpful, but is it really worth the risk if you’re significantly increasing their risk of death?” said Sullivan, who wasn’t involved in the study.
Clearly, he said, this “raises a flag that we have to look at this a little more carefully and be a little clearer with patients about the risk. One could argue that we should not be so quick to add these drugs, even though they could be helpful, before we exhaust other less potentially risky options.”
Sullivan’s advice: “Do the three trials of antidepressants, look at antidepressant combinations, don’t be quick to jump to this particular option, because of the concerns. Certainly there are situations like psychotic depression where the risk of use is outweighed by the benefits, given the clinical syndrome, but for less severe forms, we probably should reformulate some of our algorithms.”
The study was supported by the National Institute of Mental Health (NIMH). Gerhard received grants from the NIMH and the National Institute on Aging during the conduct of the study; grants and personal fees from Bristol-Myers Squibb; and personal fees from Eisai, Merck, Pfizer, Lilly, and IntraCellular Therapies outside the submitted work. Sullivan has disclosed no relevant financial relationships.