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Published in: European Child & Adolescent Psychiatry 3/2018

01-03-2018 | Original Contribution

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

Authors: Catherine Cornu, Catherine Mercier, Tiphanie Ginhoux, Sandrine Masson, Julie Mouchet, Patrice Nony, Behrouz Kassai, Valérie Laudy, Patrick Berquin, Nathalie Franc, Marie-France Le Heuzey, Hugues Desombre, Olivier Revol

Published in: European Child & Adolescent Psychiatry | Issue 3/2018

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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.
Literature
1.
go back to reference APA (2010) Diagnostic and statistical manual of mental disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association. 943 pp APA (2010) Diagnostic and statistical manual of mental disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association. 943 pp
2.
go back to reference American Psychiatric Association (1996) DSM4 V, Manuel diagnostique et statistique des troubles mentaux. Traduction française, Paris, Masson, 1056 pp American Psychiatric Association (1996) DSM4 V, Manuel diagnostique et statistique des troubles mentaux. Traduction française, Paris, Masson, 1056 pp
3.
go back to reference Cantwell DP (1996) Attention deficit disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 35(8):978–987CrossRefPubMed Cantwell DP (1996) Attention deficit disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 35(8):978–987CrossRefPubMed
4.
go back to reference 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):942–948CrossRefPubMed 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):942–948CrossRefPubMed
5.
go back to reference Faraone SV, Sergeant J, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2(2):104–113PubMedPubMedCentral Faraone SV, Sergeant J, Gillberg C, Biederman J (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2(2):104–113PubMedPubMedCentral
6.
go back to reference 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 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
8.
go back to reference Attention deficit hyperactivity disorder: diagnosis and management. NICE guidelines [CG72] Published date: September 2008 Last updated: February 2016 Attention deficit hyperactivity disorder: diagnosis and management. NICE guidelines [CG72] Published date: September 2008 Last updated: February 2016
9.
go back to reference 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):h5203CrossRef 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):h5203CrossRef
10.
go back to reference Kidwell KM, Van Dyk TR, Lundahl A, Nelson TD (2015) Stimulant medications and sleep for youth with ADHD: a meta-analysis. Pediatrics 136(6):1144–1153CrossRefPubMed Kidwell KM, Van Dyk TR, Lundahl A, Nelson TD (2015) Stimulant medications and sleep for youth with ADHD: a meta-analysis. Pediatrics 136(6):1144–1153CrossRefPubMed
12.
go back to reference 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 71:327–330CrossRef 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 71:327–330CrossRef
13.
go back to reference 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):406–411CrossRef 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):406–411CrossRef
14.
go back to reference 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–330SCrossRefPubMed 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–330SCrossRefPubMed
15.
go back to reference 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):e0156432CrossRefPubMedPubMedCentral 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):e0156432CrossRefPubMedPubMedCentral
16.
go back to reference Richardson AJ, Puri BK (2000) The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 63(1–2):79–87CrossRefPubMed Richardson AJ, Puri BK (2000) The potential role of fatty acids in attention-deficit/hyperactivity disorder. Prostaglandins Leukot Essent Fatty Acids 63(1–2):79–87CrossRefPubMed
17.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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):275–289CrossRefPubMed 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):275–289CrossRefPubMed
20.
go back to reference 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):991–1000CrossRefPubMedPubMedCentral 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):991–1000CrossRefPubMedPubMedCentral
21.
go back to reference DuPaul GJ, Power TJ, Anastopoulos AD (1998) ADHD Rating Scale IV: checklists, norms, and clinical interpretations. Guilford Press, New York (NY) DuPaul GJ, Power TJ, Anastopoulos AD (1998) ADHD Rating Scale IV: checklists, norms, and clinical interpretations. Guilford Press, New York (NY)
22.
go back to reference 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 58:1–6CrossRefPubMed 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 58:1–6CrossRefPubMed
23.
go back to reference Conners CK (1969) A teacher rating scale for use in drug studies with children. Am J Psychiatry 126(6):884–888CrossRefPubMed Conners CK (1969) A teacher rating scale for use in drug studies with children. Am J Psychiatry 126(6):884–888CrossRefPubMed
24.
go back to reference Lefavrais P. Test de l’Alouette, Éditions du Centre de Psychologie Appliquée. 2ème édition ed. 1967, Paris Lefavrais P. Test de l’Alouette, Éditions du Centre de Psychologie Appliquée. 2ème édition ed. 1967, Paris
26.
go back to reference 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):424–425CrossRefPubMed 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):424–425CrossRefPubMed
27.
go back to reference 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):1896–1901CrossRefPubMed 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):1896–1901CrossRefPubMed
28.
go back to reference 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):E83CrossRefPubMed 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):E83CrossRefPubMed
29.
go back to reference Staquet Maurice J, Hays Ron D (1998) Peter M. Methods and Practice, Fayers. Quality of Life Assessment in Clinical Trials Staquet Maurice J, Hays Ron D (1998) Peter M. Methods and Practice, Fayers. Quality of Life Assessment in Clinical Trials
30.
go back to reference 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 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
31.
go back to reference 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):496–505CrossRefPubMedPubMedCentral 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):496–505CrossRefPubMedPubMedCentral
32.
go back to reference Stevens L, Zhang W, Peck L et al (2003) EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 38(10):1007–1021CrossRefPubMed Stevens L, Zhang W, Peck L et al (2003) EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Lipids 38(10):1007–1021CrossRefPubMed
33.
go back to reference 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):1540–1549CrossRefPubMed 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):1540–1549CrossRefPubMed
34.
go back to reference 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):163–171CrossRefPubMed 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):163–171CrossRefPubMed
35.
go back to reference 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):718–730CrossRefPubMed 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):718–730CrossRefPubMed
36.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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/​S000711451200030​X. Epub 2012 Feb 28
39.
go back to reference 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):923–928CrossRefPubMed 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):923–928CrossRefPubMed
40.
go back to reference 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):189–196CrossRefPubMed 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):189–196CrossRefPubMed
Metadata
Title
A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms
Authors
Catherine Cornu
Catherine Mercier
Tiphanie Ginhoux
Sandrine Masson
Julie Mouchet
Patrice Nony
Behrouz Kassai
Valérie Laudy
Patrick Berquin
Nathalie Franc
Marie-France Le Heuzey
Hugues Desombre
Olivier Revol
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
European Child & Adolescent Psychiatry / Issue 3/2018
Print ISSN: 1018-8827
Electronic ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-017-1058-z

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