A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms

Abstract

Objective

Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids.

Methods

Children aged 6–15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children—KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised—CPRS-R), and depression (Children’s Depression Inventory—CDI).

Results

Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA–EPA group: −19 (−26, −12)  % and −9.7 (−16.6, −2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA–EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms).

Conclusion

This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms.

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References

  1. 1.

    APA (2010) Diagnostic and statistical manual of mental disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association. 943 pp

  2. 2.

    American Psychiatric Association (1996) DSM4 V, Manuel diagnostique et statistique des troubles mentaux. Traduction française, Paris, Masson, 1056 pp

  3. 3.

    Cantwell DP (1996) Attention deficit disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 35(8):978–987

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164(6):942–948

    Article  PubMed  Google Scholar 

  5. 5.

    Faraone SV, Sergeant J, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2(2):104–113

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Schachter HM, Pham B, King J, Langford S, Moher D (2001) How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CAMJ 165(11):1475–1488

    CAS  Google Scholar 

  7. 7.

    http://www.has-sante.fr/portail/upload/docs/application/pdf/2012-11/methylphenidate_reeval_annexe.pdf

  8. 8.

    Attention deficit hyperactivity disorder: diagnosis and management. NICE guidelines [CG72] Published date: September 2008 Last updated: February 2016

  9. 9.

    Storebø OJ, Krogh HB, Ramstad E, Moreira-Maia CR, Holmskov M, Skoog M, Nilausen TD, Magnusson FL, Zwi M, Gillies D, Rosendal S, Groth C, Rasmussen KB, Gauci D, Kirubakaran R, Forsbøl B, Simonsen E, Gluud C (2015) Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ 25(351):h5203

    Article  Google Scholar 

  10. 10.

    Kidwell KM, Van Dyk TR, Lundahl A, Nelson TD (2015) Stimulant medications and sleep for youth with ADHD: a meta-analysis. Pediatrics 136(6):1144–1153

    Article  PubMed  Google Scholar 

  11. 11.

    http://www.medicines.org.uk/EMC/medicine/1316/SPC/Ritalin/accessed%2030th%20November%202011#UNDESIRABLE_EFFECTS

  12. 12.

    Burgess JR, Stevens L, Zhang W, Peck L (2000) Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 71:327–330

    Article  Google Scholar 

  13. 13.

    Mitchell EA, Aman MG, Turbott SH, Manku M (1987) Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila) 26(8):406–411

    CAS  Article  Google Scholar 

  14. 14.

    Burgess JR, Stevens L, Zhang W, Peck L (2000) Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 71(1 Suppl):327S–330S

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Parletta N, Niyonsenga T, Duff J (2016) Omega-3 and omega-6 polyunsaturated fatty acid levels and correlations with symptoms in children with attention deficit hyperactivity disorder, autistic spectrum disorder and typically developing controls. PLoS ONE 11(5):e0156432

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Richardson AJ, Puri BK (2000) The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 63(1–2):79–87

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Lange KW, Hauser J, Lange KM, Makulska-Gertruda E, Nakamura Y, Reissmann A, Sakaue Y, Takeuchi Y (2017) The role of nutritional supplements in the treatment of ADHD: what the evidence says. Curr Psychiatry Rep 19(2):8

  18. 18.

    Gillies D, Sinn JKh, Lad SS, Leach MJ, Ross MJ (2012) Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev, 7: p. CD007986

  19. 19.

    Sonuga-Barke EJ, Brandeis D, Cortese S, Daley D, Ferrin M, Holtmann M, Stevenson J, Danckaerts M, van der Oord S, Döpfner M, Dittmann RW, Simonoff E, Zuddas A, Banaschewski T, Buitelaar J, Coghill D, Hollis C, Konofal E, Lecendreux M, Wong IC, Sergeant J, European ADHD Guidelines Group (2013) Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 170(3):275–289

    Article  PubMed  Google Scholar 

  20. 20.

    Bloch MH, Qawasmi A (2011) Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry 50(10):991–1000

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    DuPaul GJ, Power TJ, Anastopoulos AD (1998) ADHD Rating Scale IV: checklists, norms, and clinical interpretations. Guilford Press, New York (NY)

    Google Scholar 

  22. 22.

    Mercier C, Roche S, Gaillard S et al (2016) Partial validation of a French version of the ADHD-rating scale IV on a French population of children with ADHD and epilepsy. Factorial structure, reliability, and responsiveness. Epilepsy Behav 58:1–6

    Article  PubMed  Google Scholar 

  23. 23.

    Conners CK (1969) A teacher rating scale for use in drug studies with children. Am J Psychiatry 126(6):884–888

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Lefavrais P. Test de l’Alouette, Éditions du Centre de Psychologie Appliquée. 2ème édition ed. 1967, Paris

  25. 25.

    http://www.psytest.net/index.php?page=Kitap

  26. 26.

    Finch AJ Jr, Saylor CF, Edwards GL (1985) Children’s depression inventory: sex and grade norms for normal children. J Consult Clin Psychol 53(3):424–425

    Article  PubMed  Google Scholar 

  27. 27.

    Michelson D, Allen AJ, Busner J et al (2002) Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J Psychiatry 159(11):1896–1901

    Article  PubMed  Google Scholar 

  28. 28.

    Michelson D, Faries D, Wernicke J et al (2001) Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 108(5):E83

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Staquet Maurice J, Hays Ron D (1998) Peter M. Methods and Practice, Fayers. Quality of Life Assessment in Clinical Trials

    Google Scholar 

  30. 30.

    Goodman D, Faraone SV, Adler LA et al (2010) Interpreting ADHD rating scale scores: linking ADHD rating scale scores and CGI levels in two randomized controlled trials of Lisdexamfetamine Dimesylate in ADHD. Primary Psychiatry 17(3):44–52

    Google Scholar 

  31. 31.

    Hawkey E, Nigg JT (2014) Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev 34(6):496–505

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Stevens L, Zhang W, Peck L et al (2003) EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 38(10):1007–1021

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Gustafsson PA, Birberg-Thornberg U, Duchén K et al (2010) EPA supplementation improves teacher-rated behaviour and oppositional symptoms in children with ADHD. Acta Paediatr 99(10):1540–1549

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Itomura M, Hamazaki K, Sawazaki S et al (2005) The effect of fish oil on physical aggression in schoolchildren—a randomized, double-blind, placebo-controlled trial. J Nutr Biochem 16(3):163–171

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Kirby A, Woodward A, Jackson S, Wang Y, Crawford MA (2010) A double-blind, placebo-controlled study investigating the effects of omega-3 supplementation in children aged 8–10 years from a mainstream school population. Res Dev Disabil 31(3):718–730

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Richardson AJ, Burton JR, Sewell RP, Spreckelsen TF, Montgomery P (2012) Docosahexaenoic acid for reading, cognition and behavior in children aged 7–9 years: a randomized, controlled trial (the DOLAB Study). PLoS One 7(9):e43909. doi:10.1371/journal.pone.0043909. Epub 2012 Sep 6

  37. 37.

    Bos DJ, van Montfort SJ, Oranje B, Durston S, Smeets PA (2016) Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: what is the evidence? Eur Neuropsychopharmacol 26(3):546–561. doi:10.1016/j.euroneuro.2015.12.031. Epub 2015 Dec 21. Review

  38. 38.

    Vyncke KE, Libuda L, De Vriendt T, Moreno LA, Van Winckel M, Manios Y, Gottrand F, Molnar D, Vanaelst B, Sjöström M, González-Gross M, Censi L, Widhalm K, Michels N, Gilbert CC, Xatzis C, Cuenca García M, de Heredia FP, De Henauw S, Huybrechts I; HELENA consortium (2012) Dietary fatty acid intake, its food sources and determinants in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Br J Nutr 108(12):2261–273. doi:10.1017/S000711451200030X. Epub 2012 Feb 28

  39. 39.

    Koletzko B, Uauy R, Palou A, Kok F, Hornstra G, Eilander A, Moretti D, Osendarp S, Zock P, Innis S (2010) Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in children—a workshop report. Br J Nutr 103(6):923–928

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Voigt RG, Llorente AM, Jensen CL, Fraley JK, Berretta MC, Heird WC (2001) A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder. J Pediatr 139(2):189–196

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Catherine Cornu.

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Cornu, C., Mercier, C., Ginhoux, T. et al. A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms. Eur Child Adolesc Psychiatry 27, 377–384 (2018). https://doi.org/10.1007/s00787-017-1058-z

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Keywords

  • Child ADHD
  • Omega-3 rich fatty acid supplementation
  • Randomized controlled trial