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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. Albrecht
  • Vani Rao
  • Eleanor M. Perfetto
  • C. Daniel Mullins
Original Research Article

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Notes

Acknowledgements

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

Funding

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 NHCouncil.org. 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)

References

  1. 1.
    Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths—United States, 2007 and 2013. Morbidity and mortality weekly report surveillance summaries (Washington, DC: 2002). 2017;66(9):1–16.Google Scholar
  2. 2.
    Rapoport MJ, Kiss A, Feinstein A. The impact of major depression on outcome following mild-to-moderate traumatic brain injury in older adults. J Affect Disord. 2006;92(2–3):273–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Albrecht JS, Kiptanui Z, Tsang Y, Khokhar B, Liu X, Simoni-Wastila L, et al. Depression among older adults after traumatic brain injury: a national analysis. Am J Geriatr Psychiatry. 2015;23(6):607–14.CrossRefPubMedGoogle Scholar
  4. 4.
    Jorge RE, Robinson RG, Starkstein SE, Arndt SV. Influence of major depression on 1-year outcome in patients with traumatic brain injury. J Neurosurg. 1994;81(5):726–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Rapoport MJ, Herrmann N, Shammi P, Kiss A, Phillips A, Feinstein A. Outcome after traumatic brain injury sustained in older adulthood: a one-year longitudinal study. Am J Geriatr Psychiatry. 2006;14(5):456–65.CrossRefPubMedGoogle Scholar
  6. 6.
    Utomo WK, Gabbe BJ, Simpson PM, Cameron PA. Predictors of in-hospital mortality and 6-month functional outcomes in older adults after moderate to severe traumatic brain injury. Injury. 2009;40(9):973–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Fann JR, Hart T, Schomer KG. Treatment for depression after traumatic brain injury: a systematic review. J Neurotrauma. 2009;26(12):2383–402.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, et al. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006;23(10):1468–501.CrossRefPubMedGoogle Scholar
  9. 9.
    Rao V, Koliatsos V, Ahmed F, Lyketsos C, Kortte K. Neuropsychiatric disturbances associated with traumatic brain injury: a practical approach to evaluation and management. Semin Neurol. 2015;35(1):64–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Lee HB, Lyketsos CG, Rao V. Pharmacological management of the psychiatric aspects of traumatic brain injury. Int R Psychiatry (Abingdon, England). 2003;15(4):359–70.CrossRefGoogle Scholar
  11. 11.
    Albrecht JS, Liu X, Smith GS, Baumgarten M, Rattinger GB, Gambert SR, et al. Stroke incidence following traumatic brain injury in older adults. J Head Trauma Rehabil. 2015;30(2):62–7.CrossRefGoogle Scholar
  12. 12.
    Englander J, Cifu DX, Diaz-Arrastia R. Information/education page. Seizures and traumatic brain injury. Arch Phys Med Rehabil. 2014;95(6):1223–4.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Yeh CC, Chen TL, Hu CJ, Chiu WT, Liao CC. Risk of epilepsy after traumatic brain injury: a retrospective population-based cohort study. J Neurol Neurosurg Psychiatry. 2013;84(4):441–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Bloechliger M, Ceschi A, Ruegg S, Kupferschmidt H, Kraehenbuehl S, Jick SS, et al. Risk of seizures associated with antidepressant use in patients with depressive disorder: follow-up study with a nested case-control analysis using the Clinical Practice Research Datalink. Drug Saf. 2016;39(4):307–21.CrossRefPubMedGoogle Scholar
  15. 15.
    Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, Hippisley-Cox J. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ (Clinical research ed). 2011;2(343):d4551.CrossRefGoogle Scholar
  16. 16.
    Hackam DG, Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis. Neurology. 2012;79(18):1862–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Hill T, Coupland C, Morriss R, Arthur A, Moore M, Hippisley-Cox J. Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database. BMC Psychiatry. 2015;17(15):315.CrossRefGoogle Scholar
  18. 18.
    Renoux C, Vahey S, Dell’Aniello S, Boivin JF. Association of Selective serotonin reuptake inhibitors with the risk for spontaneous intracranial hemorrhage. JAMA Neurol. 2017;74(2):173–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Alldredge BK. Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations. Neurology. 1999;53(5 Suppl 2):S68–75.PubMedGoogle Scholar
  20. 20.
    Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R. Effects of psychotropic drugs on seizure threshold. Drug Saf. 2002;25(2):91–110.CrossRefPubMedGoogle Scholar
  21. 21.
    The American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46.CrossRefGoogle Scholar
  22. 22.
    Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. 2006;40(9):1618–22.CrossRefPubMedGoogle Scholar
  23. 23.
    Movig KL, Leufkens HG, Lenderink AW, van den Akker VG, Hodiamont PP, Goldschmidt HM, et al. Association between antidepressant drug use and hyponatraemia: a case-control study. Br J Clin Pharmacol. 2002;53(4):363–9.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wroblewski BA, McColgan K, Smith K, Whyte J, Singer WD. The incidence of seizures during tricyclic antidepressant drug treatment in a brain-injured population. J Clin Psychopharmacol. 1990;10(2):124–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Albrecht JS, Kiptanui Z, Tsang Y, Khokhar B, Smith GS, Zuckerman IH, et al. Patterns of depression treatment in Medicare beneficiaries with depression after traumatic brain injury. J Neurotrauma. 2015;32(16):1223–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Albrecht JS, Mullins DC, Smith GS, Rao V. Psychotropic medication use among Medicare beneficiaries following traumatic brain injury. Am J Geriatr Psychiatry. 2017;25(4):415–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Albrecht JS, O’Hara LM, Moser KA, Mullins CD, Rao V. Perception of barriers to the diagnosis and receipt of treatment for neuropsychiatric disturbances after traumatic brain injury. Arch Phys Med Rehabil. 2017;98(12):2548–52.CrossRefPubMedGoogle Scholar
  28. 28.
    Marr AL, Coronado VG, editors. Central nervous system injury surveillance data submission standards—2002. Atlanta: US Department of Health and Human Services, CDC; 2004.Google Scholar
  29. 29.
    Thurman DJ, Sniezek JE, Johnson D, Greenspan A, Smith SM. Guidelines for surveillance of central nervous system injury. Atlanta: US Department of Health and Human Services, Public Health Service, CDC, National Center for Injury Prevention and Control; 1995.Google Scholar
  30. 30.
    Carroll CP, Cochran JA, Guse CE, Wang MC. Are we underestimating the burden of traumatic brain injury? Surveillance of severe traumatic brain injury using centers for disease control International classification of disease, ninth revision, clinical modification, traumatic brain injury codes. Neurosurgery. 2012;71(6):1064–70 (discussion 70).CrossRefPubMedGoogle Scholar
  31. 31.
    Rates of hospitalization related to traumatic brain injury—nine states, 2003. MMWR Morb Mortal Weekly Rep. 2007;56(8):167–70.Google Scholar
  32. 32.
    Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188–94.CrossRefPubMedGoogle Scholar
  33. 33.
    Dinan TG, Mobayed M. Treatment resistance of depression after head injury: a preliminary study of amitriptyline response. Acta Psychiatr Scand. 1992;85(4):292–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Pd A. Survival analysis using SAS®: a practical guide. Cary: SAS Institute; 1995.Google Scholar
  35. 35.
    Holm S. A simple sequentially rejective multiple test procedure. Scand J Statist. 1979;6(2):65–70.Google Scholar
  36. 36.
    de Abajo FJ. Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients. Drugs Aging. 2011;28(5):345–67.CrossRefPubMedGoogle Scholar
  37. 37.
    Fann JR, Uomoto JM, Katon WJ. Sertraline in the treatment of major depression following mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2000;12(2):226–32.CrossRefPubMedGoogle Scholar
  38. 38.
    Perino C, Rago R, Cicolini A, Torta R, Monaco F. Mood and behavioural disorders following traumatic brain injury: clinical evaluation and pharmacological management. Brain Inj. 2001;15(2):139–48.CrossRefPubMedGoogle Scholar
  39. 39.
    Turner-Stokes L, Hassan N, Pierce K, Clegg F. Managing depression in brain injury rehabilitation: the use of an integrated care pathway and preliminary report of response to sertraline. Clin Rehabil. 2002;16(3):261–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Seeger JD, Williams PL, Walker AM. An application of propensity score matching using claims data. Pharmacoepidemiol Drug Saf. 2005;14(7):465–76.CrossRefPubMedGoogle Scholar
  41. 41.
    Cole SR, Hernan MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol. 2008;168(6):656–64.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Glassman AH. Cardiovascular effects of antidepressant drugs: updated. J Clin Psychiatry. 1998;59(Suppl 15):13–8.PubMedGoogle Scholar
  43. 43.
    Glassman AH, Roose SP, Bigger JT Jr. The safety of tricyclic antidepressants in cardiac patients. Risk-benefit reconsidered. JAMA. 1993;269(20):2673–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab. 2002;3(1):13–37.CrossRefPubMedGoogle Scholar

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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