Reassuring findings
Serotonin syndrome occurred in fewer than six patients (< .5%), although the exact numbers were not reported, owing to patient privacy concerns. However, on the basis of fewer than six events, the investigators calculated the risk difference for serotonin syndrome as ranging from −0.5% to 2.3%.
Fewer patients who were taking antidepressants experienced serotonin syndrome, compared with those who were not taking antidepressants.
The investigators estimated a propensity score for antidepressant use that incorporated several patient baseline characteristics, including age, sex, rural home address, Charlson Comorbidity Index, estimated glomerular filtration rate, history of substance use disorder, and days of use of linezolid and other serotonergic medications. They then matched patients who were not taking antidepressants with those who were taking antidepressants (n = 166 each).
The adjusted risk difference for serotonin syndrome was lower in the antidepressant group than in the no-antidepressant group (−1.2%; 95% confidence interval, −2.9% to 0.5%).
“Within this 95% CI, the worst-case scenario would be a 0.5% increase in the risk of serotonin syndrome due to antidepressants, which is equivalent to a number needed to harm of 200,” the researchers write.
For secondary outcomes, they found “similar rates” of altered mental status or confusion, hospitalization, and death within 30 days between the two propensity score–matched groups.
The investigators note that their findings have “limitations, due to the nature of retrospective observational studies.” Moreover, these types of studies are “not efficient because they often focus on a particular adverse event.”
Future research should move beyond observational studies to phase 4 studies, which would “prospectively monitor for all types of adverse events,” they write.
Still, “while waiting for higher-quality evidence, our study adds to the existing evidence for the safety of linezolid even in the context of concomitant antidepressants,” the researchers note.
“Based on the existing evidence, clinicians should be reassured that it appears safe to prescribe oral linezolid to patients taking antidepressants, especially if there are limited antibiotic options or alternative antibiotic options would be inferior,” they add.
‘Consequential relevance’
Commenting on the study, Ipsit Vahia, MD, associate chief of geriatric psychiatry and director of digital psychiatry translation at McLean Hospital, Boston, noted that although studies of drug interactions across age groups “may not accurately reflect the rates of risk for older adults,” the current study focused on linezolid use among older patients.
Dr. Ipsit Vahia
“One may expect higher rates of serotonin syndrome in older adults, who generally tend to be more sensitive to adverse reactions,” said Dr. Vahia, who is also director of the Technology and Aging Lab at McLean and was not involved with the current research.
“However, the study finds the risk to be low with a number needed to harm of 200,” Dr. Vahia said.
“This retrospective epidemiologic study does not shed light on why this number may be lower than expected, but it has consequential relevance in clinical practice for the management of severe infections among older adults using antidepressants,” he added.
The study was funded by a Queen’s University Research Initiation Grant. Dr. Bai and three of the four other investigators report no relevant financial relationships. Coinvestigator Mark Loeb, MD, reports having received personal fees from the Paladin Labs Advisory Committee, the International Centre for Professional Development in Health and Medicine Advisory Committee, and the Sunovion Advisory Committee outside the submitted work. Dr. Vahia serves as a consultant for Otsuka, has a research collaboration with Emerald Innovations, and receives honorarium as editor for The American Journal of Geriatric Psychiatry.
A version of this article first appeared on Medscape.com.