Drugs & Aging

, Volume 35, Issue 8, pp 763–772 | Cite as

Safety of Antidepressant Classes Used Following Traumatic Brain Injury Among Medicare Beneficiaries: A Retrospective Cohort Study

  • Jennifer S. AlbrechtEmail author
  • Vani Rao
  • Eleanor M. Perfetto
  • C. Daniel Mullins
Original Research Article



There is poor evidence supporting the use of any pharmacologic treatments for neuropsychiatric disorders following traumatic brain injury (TBI), especially among older adults. Informed by our recent characterization of psychotropic medication use among Medicare beneficiaries with TBI, the objective of this study was to compare the risk of several adverse events associated with use of the three most commonly used classes of antidepressants following TBI in this population.


We conducted a retrospective cohort study using administrative claims data from US Medicare beneficiaries hospitalized with TBI between 2006 and 2010 (n = 30,886). We assessed monthly selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and tricyclic antidepressant (TCA) use. We identified adverse events associated with these drug classes that were available in administrative claims data from studies in TBI and non-TBI populations: seizures, hemorrhagic stroke, ischemic stroke, gastrointestinal bleed, hyponatremia, and fractures. We made comparisons between antidepressant classes to assess excess risk of each adverse event using discrete time analysis and controlling for potential confounders.


SSRIs were the most commonly used of the antidepressant classes, followed by SNRIs and TCAs. We observed a total of 23,021 adverse events. Ischemic stroke was the most frequent (8296 events). Hemorrhagic stroke (1706 events) and seizures (1841) were least often observed. Compared with TCAs, SSRI use was associated with an increased risk of hemorrhagic stroke (risk ratio 2.47; 95% confidence interval 1.30–4.70). No other antidepressant class comparisons were associated with increased risk of adverse events.


Compared with SSRIs, use of SNRIs and TCAs following hospitalization for TBI among Medicare beneficiaries was not associated with an increased risk of any of the studied adverse events. Compared to TCAs, SSRI use was associated with increased risk of hemorrhagic stroke. This information may help guide patients and prescribers in selecting antidepressants for older adults following TBI.



The authors would like to thank Susan dosReis, PhD, University of Maryland School of Pharmacy, for her thorough review of this paper. Dr. dosReis has no conflicts of interest.

Compliance with Ethical Standards


Dr. Albrecht was supported by Agency for Healthcare Quality and Research grant 1K01HS024560. Dr. Rao was supported by DOD grant W81XWH-13-1-0469.

Conflict of interest

Dr. Mullins has received grants from Bayer, Novartis, and Pfizer and consulting income from Bayer, Janssen/J&J, Novo Nordisk, Pfizer, Regeneron, and Sanofi. Dr. Perfetto is employed by the National Health Council in Washington, DC, which accepts membership dues and sponsorships from a variety of organizations and companies. For the full list of members and sponsors, please see Drs. Albrecht and Rao declare no conflicts of interest.

Supplementary material

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Supplementary material 1 (DOCX 12 kb)
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Supplementary material 2 (DOCX 12 kb)
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Supplementary material 3 (DOCX 13 kb)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Epidemiology and Public HealthUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Department of Psychiatry and Behavioral SciencesJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Pharmaceutical Health Services ResearchUniversity of Maryland School of PharmacyBaltimoreUSA
  4. 4.National Health CouncilWashington, DCUSA

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