Red Blood Cell Omega-3 Fatty Acid Composition and Psychotropic Drug Use in Older Adults: Results from the MAPT Study

  • Adeline GalliniEmail author
  • A. Yrondi
  • C. Cantet
  • M. Poncet
  • B. Vellas
  • L. Schmitt
  • S. Andrieu
  • DSA/MAPT Study Group


Low docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration has been associated with the development of some psychiatric disorders


to assess the association between red blood cell (RBC) DHA-EPA concentration and psychotropic drug use in older adults and between the 1-year change in RBC DHA-EPA and psychotropic drug use at 12 months. Design: secondary analysis of multicenter, randomized controlled trial testing multidomain intervention and/or n-3 PUFA supplement on cognitive function (MAPT study).


France, 2008–2014.


1680 participants ≥70 years, community-dwelling were included.


Psychotropic drug use was self-reported during medical interviews and assessments. RBC n-3 PUFA concentration was defined by % of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) among total fatty acids. Logistic regressions models controlling for age, sex, education, depression risk and intervention group were used.


1594 participants had baseline DHA-EPA concentration available (mean age=75.5±4.5 years, 65% females). At baseline, participants with DHA-EPA ≤4.82% (lowest quartile) reported higher prevalence of use of overall psychotropic drugs (34.0% vs 24.4%; aOR=1.33, 95%CI=[1.03–1.72]), anxiolytic/hypnotic drugs (25.0% vs 18.2%; aOR=1.42, 95%CI=[1.07–1.89]), and antidepressants (18.3% vs 13.5%; aOR=1.25, 95%CI=[0.93–1.72]) than participants with higher DHA-EPA. Participants who experienced an increase in DHA-EPA from baseline were less likely to use a psychotropic drug at 12 months than participants with no change or a decrease (aOR=0.72, 95%CI=[0.55–0.96]).


Low RBC DHAEPA concentration was independently associated with psychotropic drug use. Future studies are needed to assess whether low RBC DHA-EPA is a risk marker for psychotropic drug use in older adults and to better understand underlying pathophysiological mechanisms. Registration number: database (NCT00672685).

Key words

psychotropic drug use omega-3 fatty acids elderly prevention 


Acknowledgments / Funding

The MAPT study was supported by grants from the Gérontopôle of Toulouse, the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the omega-3 supplement), Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc. The promotion of this study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the Association Monegasque pour la Recherche sur la maladie d’Alzheimer (AMPA) and the UMR 1027 Unit INSERM-University of Toulouse III.

Conflicts of Interests: The MAPT study was supported by grants from the French Ministry of Health (PHRC 2008, 2009), Pierre Fabre Research Institute (manufacturer of the omega-3 supplement), Exhonit Therapeutics SA, and Avid Radiopharmaceuticals Inc.

Ethical Standards: The present experiments comply with the current laws of the country in which they were performed.

Supplementary material

12603_2019_1252_MOESM1_ESM.docx (92 kb)
Supplementary material, approximately 92.3 KB.


  1. 1.
    Guixà-González, R.; Javanainen, M.; Gómez-Soler, M.; Cordobilla, B.; Domingo, J. C.; Sanz, F.; Pastor, M.; Ciruela, F.; Martinez-Seara, H.; Selent, J. Membrane Omega-3 Fatty Acids Modulate the Oligomerisation Kinetics of Adenosine A2A and Dopamine D2 Receptors. Sci. Rep., 2016;6, 19839. doi: Scholar
  2. 2.
    Pusceddu, M. M.; Kelly, P.; Stanton, C.; Cryan, J. F.; Dinan, T. G. N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology. Int. J. Neuropsychopharmacol. 2016;19(12). doi:
  3. 3.
    McNamara, R. K.; Welge, J. A. Meta-Analysis of Erythrocyte Polyunsaturated Fatty Acid Biostatus in Bipolar Disorder. Bipolar Disord. 2016;18(3), 300–306. doi: Scholar
  4. 4.
    Tiemeier, H.; van Tuijl, H. R.; Hofman, A.; Kiliaan, A. J.; Breteler, M. M. B. Plasma Fatty Acid Composition and Depression Are Associated in the Elderly: The Rotterdam Study. Am. J. Clin. Nutr. 2003;78(1), 40–46. doi: Scholar
  5. 5.
    Liu, J. J.; Galfalvy, H. C.; Cooper, T. B.; Oquendo, M. A.; Grunebaum, M. F.; Mann, J. J.; Sublette, M. E. Omega-3 Polyunsaturated Fatty Acid (PUFA) Status in Major Depressive Disorder with Comorbid Anxiety Disorders. J. Clin. Psychiatry, 74 2013;(7), 732–738. doi: Scholar
  6. 6.
    Dangour, A. D.; Allen, E.; Elbourne, D.; Fasey, N.; Fletcher, A. E.; Hardy, P.; Holder, G. E.; Knight, R.; Letley, L.; Richards, M.; et al. Effect of 2-y n-3 Long-Chain Polyunsaturated Fatty Acid Supplementation on Cognitive Function in Older People: A Randomized, Double-Blind, Controlled Trial. Am. J. Clin. Nutr. 2010;91(6), 1725–1732. doi: Scholar
  7. 7.
    Dangour, A. D.; Whitehouse, P. J.; Rafferty, K.; Mitchell, S. A.; Smith, L.; Hawkesworth, S.; Vellas, B. B-Vitamins and Fatty Acids in the Prevention and Treatment of Alzheimer’s Disease and Dementia: A Systematic Review. J. Alzheimers Dis. JAD, 2010;22(1), 205–224. doi: Scholar
  8. 8.
    Alonso, J.; Angermeyer, M. C.; Bernert, S.; Bruffaerts, R.; Brugha, T. S.; Bryson, H.; de Girolamo, G.; Graaf, R.; Demyttenaere, K.; Gasquet, I.; et al. Psychotropic Drug Utilization in Europe: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) Project. Acta Psychiatr. Scand. Suppl. 2004;No. 420, 55–64. doi: Scholar
  9. 9.
    Ohayon, M. M.; Lader, M. H. Use of Psychotropic Medication in the General Population of France, Germany, Italy, and the United Kingdom. J. Clin. Psychiatry 2002;63(9), 817–825.CrossRefGoogle Scholar
  10. 10.
    Maust, D. T.; Chen, S. H.; Benson, A.; Mavandadi, S.; Streim, J. E.; DiFilippo, S.; Snedden, T. M.; Oslin, D. W. Older Adults Recently Started on Psychotropic Medication: Where Are the Symptoms? Int. J. Geriatr. Psychiatry, 2015;30(6), 580–586. doi: Scholar
  11. 11.
    Vellas, B.; Carrie, I.; Gillette-Guyonnet, S.; Touchon, J.; Dantoine, T.; Dartigues, J. F.; Cuffi, M. N.; Bordes, S.; Gasnier, Y.; Robert, P.; et al. MAPT study: a multidomain approach for preventing alzheimer’s disease: design and baseline data. J. Prev. Alzheimers Dis. 2014;1(1), 13–22.Google Scholar
  12. 12.
    Lawton, M. P.; Brody, E. M. Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living. The Gerontologist, 1969;9(3), 179–186.CrossRefGoogle Scholar
  13. 13.
    Folstein, M. F.; Folstein, S. E.; McHugh, P. R. “Mini-Mental State”. A Practical Method for Grading the Cognitive State of Patients for the Clinician. J. Psychiatr. Res. 1975;12(3), 189–198.CrossRefGoogle Scholar
  14. 14.
    Katz, S.; Ford, A. B.; Moskowitz, R. W.; Jackson, B. A.; Jaffe, M. W. Studies of Illness in the Aged. The Index of ADL: A Standardized Measure of Biological and Psychosocial Function. JAMA J. Am. Med. Assoc., 1963;185, 914–919.CrossRefGoogle Scholar
  15. 15.
    Andrieu, S.; Guyonnet, S.; Coley, N.; Cantet, C.; Bonnefoy, M.; Bordes, S.; Bories, L.; Cufi, M.-N.; Dantoine, T.; Dartigues, J.-F.; et al. Effect of Long-Term Omega 3 Polyunsaturated Fatty Acid Supplementation with or without Multidomain Intervention on Cognitive Function in Elderly Adults with Memory Complaints (MAPT): A Randomised, Placebo-Controlled Trial. Lancet Neurol. 2017;16(5), 377–389. doi: Scholar
  16. 16.
    World Health Organisation Collaborating Centre for Drug Statistics Methodology. ATC / DDD Index.Google Scholar
  17. 17.
    Harris, W. S.; Thomas, R. M. Biological Variability of Blood Omega-3 Biomarkers. Clin. Biochem. 2010;43(3), 338–340. doi: Scholar
  18. 18.
    Fried, L. P.; Tangen, C. M.; Walston, J.; Newman, A. B.; Hirsch, C.; Gottdiener, J.; Seeman, T.; Tracy, R.; Kop, W. J.; Burke, G.; et al. Frailty in Older Adults: Evidence for a Phenotype. J. Gerontol. A. Biol. Sci. Med. Sci. 2001;56(3), M146–156.CrossRefGoogle Scholar
  19. 19.
    Fried, L. P.; Ferrucci, L.; Darer, J.; Williamson, J. D.; Anderson, G. Untangling the Concepts of Disability, Frailty, and Comorbidity: Implications for Improved Targeting and Care. J. Gerontol. A. Biol. Sci. Med. Sci. 2004;59(3), 255–263.CrossRefGoogle Scholar
  20. 20.
    Yesavage, J. A.; Brink, T. L.; Rose, T. L.; Lum, O.; Huang, V.; Adey, M.; Leirer, V. O. Development and Validation of a Geriatric Depression Screening Scale: A Preliminary Report. J. Psychiatr. Res. 1982;17(1), 37–49.CrossRefGoogle Scholar
  21. 21.
    Johnell, K.; Fastbom, J.; Rosén, M.; Leimanis, A. Inappropriate Drug Use in the Elderly: A Nationwide Register-Based Study. Ann. Pharmacother. 2007;41(7), 1243–1248. doi: Scholar
  22. 22.
    Johnell, K.; Fastbom, J. The Use of Benzodiazpines and Related Drugs amongst Older People in Sweden: Associated Factors and Concomitant Use of Other Psychotropics. Int. J. Geriatr. Psychiatry, 2009;24(7), 731–738. doi: Scholar
  23. 23.
    Haider, S. I.; Johnell, K.; Weitoft, G. R.; Thorslund, M.; Fastbom, J. The Influence of Educational Level on Polypharmacy and Inappropriate Drug Use: A Register-Based Study of More than 600,000 Older People. J. Am. Geriatr. Soc. 2009;57(1), 62–69. doi: Scholar
  24. 24.
    Parker, G.; Gibson, N. A.; Brotchie, H.; Heruc, G.; Rees, A.-M.; Hadzi-Pavlovic, D. Omega-3 Fatty Acids and Mood Disorders. Am. J. Psychiatry, 2006;163(6), 969–978. doi: Scholar
  25. 25.
    Lucas, M.; Mirzaei, F.; O’Reilly, E. J.; Pan, A.; Willett, W. C.; Kawachi, I.; Koenen, K.; Ascherio. A. Dietary Intake of N-3 and n-6 Fatty Acids and the Risk of Clinical Depression in Women: A 10-y Prospective Follow-up Study. Am. J. Clin. Nutr, 2011;93(6), 1337–1343. doi: Scholar
  26. 26.
    Féart, C.; Peuchant, E.; Letenneur, L.; Samieri, C.; Montagnier, D.; Fourrier-Reglat, A.; Barberger-Gateau, P. Plasma. Eicosapentaenoic Acid Is Inversely Associated with Severity of Depressive Symptomatology in the Elderly: Data from the Bordeaux Sample of the Three-City Study. Am. J. Clin. Nutr. 2008;87(5), 1156–1162. doi: Scholar
  27. 27.
    Montgomery, P.; Richardson, A. J. Omega-3 Fatty Acids for Bipolar Disorder. Cochrane Database Syst. Rev. 2008;No. 2, CD005169. doi: Scholar
  28. 28.
    Mello, A. H.; Gassenferth, A.; Souza, L. R.; Fortunato, J. J.; Rezin, G. T. ω-3 and Major Depression: A Review. Acta Neuropsychiatr. 2014;26(3), 178–185. doi: Scholar
  29. 29.
    Appleton, K. M.; Sallis, H. M.; Perry, R.; Ness, A. R.; Churchill, R. Omega-3 Fatty Acids for Depression in Adults. Cochrane Database Syst. Rev. 2015;No. 11, CD004692. doi: Scholar
  30. 30.
    Cockayne, N. L.; Duffy, S. L.; Bonomally, R.; English, A.; Amminger, P. G.; Mackinnon, A.; Christensen, H. M.; Naismith, S. L.; Hickie, I. B. The Beyond Ageing Project Phase 2—a Double-Blind, Selective Prevention, Randomised, Placebo-Controlled Trial of Omega-3 Fatty Acids and Sertraline in an Older Age Cohort at Risk for Depression: Study Protocol for a Randomized Controlled Trial. Trials, 2015;16, 247. doi: Scholar

Copyright information

© Serdi and Springer-Verlag International SAS, part of Springer Nature 2019

Authors and Affiliations

  • Adeline Gallini
    • 1
    • 2
    • 3
    • 6
    Email author
  • A. Yrondi
    • 2
    • 4
  • C. Cantet
    • 1
    • 2
    • 5
  • M. Poncet
    • 3
  • B. Vellas
    • 1
    • 2
    • 5
  • L. Schmitt
    • 2
    • 4
  • S. Andrieu
    • 1
    • 2
    • 3
  • DSA/MAPT Study Group
  1. 1.UMR 1027InsermToulouseFrance
  2. 2.Université Paul Sabatier Toulouse IIIToulouseFrance
  3. 3.CHU Toulouse, Service d’EpidémiologieToulouseFrance
  4. 4.CHU Toulouse, Service de PsychiatrieToulouseFrance
  5. 5.CHU Toulouse, GérontopôleToulouseFrance
  6. 6.Epidemiology DepartmentToulouse CedexFrance

Personalised recommendations