European Child & Adolescent Psychiatry

, Volume 27, Issue 3, pp 267–277 | Cite as

ADHD is associated with migraine: a systematic review and meta-analysis

  • Haitham Salem
  • David Vivas
  • Fei Cao
  • Iram F. Kazimi
  • Antonio L. Teixeira
  • Cristian P. Zeni


An association between primary headaches and attention-deficit/hyperactivity disorder (ADHD) has long been suggested. Moreover, headache is regarded as a common side effect of stimulants, the most effective treatment for ADHD. So far, no systematic review has evaluated the potential association between ADHD and headache. We performed a systematic review of the literature and a meta-analysis of all reported studies on ADHD and primary headaches. Our analysis showed a positive association between ADHD and migraine (OR 1.322, 95% CI 1.018–1717, p value 0.036), but not with tension-type headache. There is a significant association between migraine and ADHD. The mechanisms underlying this association remain to be elucidated, warranting further studies.


ADHD Headache Migraine Tension-type headache Meta-analysis Stimulants 


Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interests associated and that no funding of any kind is associated with this work.


  1. 1.
    Moffitt TE, Houts R, Asherson P et al (2015) Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a four-decade longitudinal cohort study. Am J Psychiatry 172(10):967–977. doi: 10.1176/appi.ajp.2015.14101266 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Caye A, Rocha TB, Anselmi L et al (2016) Attention-deficit/hyperactivity disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome. JAMA Psychiatry 73(7):705–712. doi: 10.1001/jamapsychiatry.2016.0383 CrossRefPubMedGoogle Scholar
  3. 3.
    Garner AA, O’Connor BC, Narad ME et al (2013) The relationship between ADHD symptom dimensions, clinical correlates, and functional impairments. J Dev Behav Pediatr 34(7):469–477CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Saylor KE, Amann BH (2016) Impulsive aggression as a comorbidity of attention-deficit/hyperactivity disorder in children and adolescents. J Child Adolesc Psychopharmacol 26(1):19–25. doi: 10.1089/cap.2015.0126 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Halmøy A, Fasmer OB, Gillberg C et al (2009) Occupational outcome in adult ADHD: impact of symptom profile, comorbid psychiatric problems and treatment: a cross sectional study of 414 clinically diagnosed adult ADHD patients. J Atten Disord 13:75–87CrossRefGoogle Scholar
  6. 6.
    Cortese S, Angriman M, Maffeis C et al (2008) Attention-deficit/hyperactivity disorder (ADHD) and obesity: a systematic review of the literature. Crit Rev Food Sci Nutr 48:524–537CrossRefPubMedGoogle Scholar
  7. 7.
    Ozge A, Sasmaz T, Cakmak SE et al (2010) Epidemiological-based childhood headache natural history study: after an interval of six years. Cephalalgia 30:703–712CrossRefPubMedGoogle Scholar
  8. 8.
    Gunner KB, Smith HD (2007) Practice guideline for diagnosis and management of migraine headaches in children and adolescents: part one. J Pediatr Health Care 21:327–332CrossRefPubMedGoogle Scholar
  9. 9.
    Oakley CB, Kossoff EH (2014) Migraine and epilepsy in pediatric population. Curr Pain Headache Rep 18(3):402. doi: 10.1007/s11916-013-0402-3 CrossRefPubMedGoogle Scholar
  10. 10.
    Smitherman TA, Burch R, Sheikh H et al (2013) The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache 53(3):427–436. doi: 10.1111/head.12074 CrossRefPubMedGoogle Scholar
  11. 11.
    Agarwal R, Goldenberg M, Perry R et al (2012) The quality of life of adults with attention deficit hyperactivity disorder: a systematic review. Innov Clin Neurosci 9(5–6):10–21PubMedPubMedCentralGoogle Scholar
  12. 12.
    Instanes JT, Klungsoyr K, Halmoy A, et al. Adult ADHD and comorbid somatic disease: a systematic literature review. J Atten Disord. 2016. doi: 10.1177/1087054716669589
  13. 13.
    Zeni CP, Guimarães AP, Polanczyk GV et al (2007) No significant association between response to methylphenidate and genes of the dopaminergic and serotonergic systems in a sample of Brazilian children with attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 144B(3):391–394CrossRefPubMedGoogle Scholar
  14. 14.
    Albers L, von Kries R, Heinen F et al (2015) Headache in school children: Is the prevalence increasing? Curr Pain Headache Rep 19:4. doi: 10.1007/s11916015-0477-0 CrossRefPubMedGoogle Scholar
  15. 15.
    Mahajnah M, Sharkia R, Shorbaji N et al (2017) The clinical characteristics of ADHD diagnosed in adolescents in comparison with younger children. J Atten Disord 1:1087054717696768. doi: 10.1177/1087054717696768 Google Scholar
  16. 16.
    American Psychiatric Association (1980) Diagnostic and statistical manual of mental disorders, 3rd edn. APA, Washington, DCGoogle Scholar
  17. 17.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. APA, Washington, DCGoogle Scholar
  18. 18.
    Headache Classification Committee of the International Headache Society (2004) The international classification of headache disorders: 2nd edition. Cephalalgia 24(Suppl. 1):9–160Google Scholar
  19. 19.
    Truman BI, Smith-Akin CK, Hinman AR et al (2000) Developing the Guide to Community Preventive Services—overview and rationale. The Task Force on Community Preventive Services. Am J Prev Med 18(1 Suppl):18–26CrossRefPubMedGoogle Scholar
  20. 20.
    Briss PA, Brownson RC, Fielding JE et al (2004) Developing and using the Guide to Community Preventive Services: lessons learned about evidence-based public health. Annu Rev Public Health 25:281–302CrossRefPubMedGoogle Scholar
  21. 21.
    Fasmer OB, Riise T, Lund A et al (2012) Comorbidity of migraine with ADHD. J Atten Disord 16(4):339–345. doi: 10.1177/1087054710385784 CrossRefPubMedGoogle Scholar
  22. 22.
    Fasmer OB, Halmoy A, Oedegaard KJ et al (2011) Adult attention deficit hyperactivity disorder is associated with migraine headaches. Eur Arch Psychiatry Clin Neurosci 261(8):595–602. doi: 10.1007/s00406-011-0203-9 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Arruda MA, Arruda R (2014) Psychological adjustment in children with episodic migraine: a population-based study. Psychol Neurosci 7:33–41. doi: 10.3922/j.psns.2014.1.06 CrossRefGoogle Scholar
  24. 24.
    Genizi J, Gordon S, Kerem NC et al (2013) Primary headaches, attention deficit disorder and learning disabilities in children and adolescents. J Headache Pain 14:54. doi: 10.1186/1129-2377-14-54 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Pavone P, Rizzo R, Conti I et al (2012) Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 25(4):1083–1091CrossRefPubMedGoogle Scholar
  26. 26.
    Riva D, Usilla A, Aggio F et al (2012) Attention in children and adolescents with headache. Headache 52(3):374–384. doi: 10.1111/j.1526-4610.2011.02033.x CrossRefPubMedGoogle Scholar
  27. 27.
    Genizi J, Marom D, Srugo I, et al. The relations between attention deficit hyperactivity disorder and headaches in a non-clinical sample of adolescents. Acad J Ped Neonatolo. 2016;2(2):AJPN.MS.ID.555583Google Scholar
  28. 28.
    Strine TW, Okoro CA, McGuire LC et al (2006) The associations among childhood headaches, emotional and behavioral difficulties, and health care use. Pediatrics 117(5):1728–1735CrossRefPubMedGoogle Scholar
  29. 29.
    Lateef TM, Merikangas KR, He J et al (2009) Headache in a national sample of american children: prevalence and comorbidity. J Child Neurol 24(5):536–543. doi: 10.1177/0883073808327831 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Pitrou I, Shojaei T, Chan-Chee C et al (2010) The associations between headache and psychopathology: a survey in school children. Headache 50:1537–1548. doi: 10.1111/j.1526-4610.2010.01781.x CrossRefPubMedGoogle Scholar
  31. 31.
    Jameson ND, Sheppard BK, Lateef T et al (2016) Medical comorbidity of attention-deficit/hyperactivity disorder in US adolescents. J Child Neurol 31(11):1282–1289CrossRefPubMedGoogle Scholar
  32. 32.
    Arruda MA, Bigal ME (2012) Migraine and migraine subtypes in preadolescent children: association with school performance. Neurology 79(18):1881–1888. doi: 10.1212/WNL.0b013e318271f812 CrossRefPubMedGoogle Scholar
  33. 33.
    Arruda MA, Guidetti V, Galli F et al (2010) Migraine, tension-type headache, and attention-deficit/hyperactivity disorder in childhood: a population-based study. Postgrad Med 122(5):18–26. doi: 10.3810/pgm.2010.09.2197 CrossRefPubMedGoogle Scholar
  34. 34.
    Mazzone L, Vitiello B, Incorpora G et al (2006) Behavioural and temperamental characteristics of children and adolescents suffering from primary headache. Cephalalgia 26(2):194–201CrossRefPubMedGoogle Scholar
  35. 35.
    Reddy DS (2013) Current pharmacotherapy of attention deficit hyperactivity disorder. Drugs Today (Barc) 49(10):647–665. doi: 10.1358/dot.2013.49.10.2008996 Google Scholar
  36. 36.
    Clavenna A, Bonati M (2014) Safety of medicines used for ADHD in children: a review of published prospective clinical trials. Arch Dis Child 99(9):866–872. doi: 10.1136/archdischild-2013-304170 CrossRefPubMedGoogle Scholar
  37. 37.
    Leviton A (1986) Do learning handicaps and headache cluster? J Child Neurol 1:372–377CrossRefPubMedGoogle Scholar
  38. 38.
    Calandre EP, Bembibre J, Arnedo ML et al (2002) Cognitive disturbances and regional cerebral blood flow abnormalities in migraine patients: their relationship with the clinical manifestations of the illness. Cephalalgia 22:291–302CrossRefPubMedGoogle Scholar
  39. 39.
    Bellini B, Arruda M, Cescut A et al (2013) Headache and comorbidity in children and adolescents. J Headache Pain 14(1):79. doi: 10.1186/1129-2377-14-79 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Gümüş YY, Çakin Memik N, Ağaoğlu B (2015) Anxiety disorders comorbidity in children and adolescents with attention deficit hyperactivity disorder. Noro Psikiyatr Ars 52(2):185–193. doi: 10.5152/npa.2015.7024 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Eyre O, Langley K, Stringaris A et al (2017) Irritability in ADHD: associations with depression liability. J Affect Disord 25(215):281–287. doi: 10.1016/j.jad.2017.03.050 CrossRefGoogle Scholar
  42. 42.
    Özdemir O, Boysan M, Güzel Özdemir P et al (2015) Relations between post-traumatic stress disorder, dissociation and attention deficit/hyperactivity disorder among earthquake survivors. Noro Psikiyatr Ars 52(3):252–257. doi: 10.5152/npa.2015.7616 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Berkol TD, Yargiç İ, Özyildirim İ et al (2014) Comorbidity of adult attention deficit and hyperactivity disorder in bipolar patients: prevalence, sociodemographic and clinical correlates. Noro Psikiyatr Ars 51(2):97–102. doi: 10.4274/npa.y6376 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Son YD, Han DH, Kim SM et al (2017) A functional connectivity comparison between attention deficit hyperactivity disorder and bipolar disorder in medication-naïve adolescents with mood fluctuation and attention problems. Psychiatry Res 17(263):1–7. doi: 10.1016/j.pscychresns.2017.02.006 CrossRefGoogle Scholar
  45. 45.
    McGough JJ, Smalley SL, McCracken JT et al (2005) Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families. Am J Psychiatry 162(9):1621–1627CrossRefPubMedGoogle Scholar
  46. 46.
    Kessler RC, Adler L, Barkley R et al (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716–723CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Villa TR, Correa Moutran AR, Sobirai Diaz LA et al (2009) Visual attention in children with migraine: a controlled comparative study. Cephalalgia 29:631–634. doi: 10.1111/j.1468-2982.2008.01767.x CrossRefPubMedGoogle Scholar
  48. 48.
    Biederman J, Ball SW, Monuteaux MC et al (2008) New insights into the comorbidity between ADHD and major depression in adolescent and young adult females. J Am Acad Child Adolesc Psychiatry 47(4):426–434CrossRefPubMedGoogle Scholar
  49. 49.
    Edden RAE, Crocetti D, Zhu H et al (2012) Reduced GABA concentration in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 69(7):750–753CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Naaijen J, Bralten J, Poelmans G et al (2017) Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism. Transl Psychiatry 7(1):e999. doi: 10.1038/tp.2016.273 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Camarda C, Monastero R, Pipia C et al (2007) Interictal executive disfunction in migraineurs without aura: relationship with duration and intensity o attacks. Cephalalgia 27:1094–1110CrossRefPubMedGoogle Scholar
  52. 52.
    Williams NM, Zaharieva I, Martin A et al (2010) Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376(9750):1401–1408. doi: 10.1016/S0140-6736(10)61109-9 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kattimani S, Mahadevan S (2011) Treating children with attention-deficit/hyperactivity disorder and comorbid epilepsy. Ann Indian Acad Neurol 14(1):9–11. doi: 10.4103/0972-2327.78042 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kim EH, Yum MS, Kim HW, Ko TS (2014) Attention-deficit/hyperactivity disorder and attention impairment in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav 37:54–58. doi: 10.1016/j.yebeh.2014.05.030 CrossRefPubMedGoogle Scholar
  55. 55.
    Kanemura H, Sano F, Ishii S, Ohyama T, Sugita K, Aihara M (2013) Characteristics of headache in childer with epilepsy. Seizure 22(8):647–650CrossRefPubMedGoogle Scholar
  56. 56.
    Papetti L, Nicita F, Parisi P, Spalice A, Villa MP, Trenite DGAK (2013) Headache and epilepsy—how are they connected? Epilepsy Behav 26(3):386–393CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang C, Kutyifa V, Moss AJ, McNitt S, Zareba W, Kaufman ES (2015) Long-QT syndrome and therapy for attention deficit/hyperactivity disorder. J Cardiovasc Electrophysiol 26(10):1039–1044. doi: 10.1111/jce.12739 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Paisley RD, Arora HS, Nazeri A, Massumi A, Razavi M (2009) Migraine and vasodepressor syncope in a large family. Tex Heart Inst J 36(5):468–469PubMedPubMedCentralGoogle Scholar
  59. 59.
    Curfman D, Chilungu M, Daroff RB, Alshekhlee A, Chelimsky G, Chelimsky TC (2012) Syncopal migraine. Clin Auton Res 22(1):17–23. doi: 10.1007/s10286-011-0141-7 CrossRefPubMedGoogle Scholar
  60. 60.
    Parisi P, Verrotti A, Paolino MC, Ferretti A, Raucci U, Moavero R, Villa MP, Curatolo P (2014) Headache and attention deficit and hyperactivity disorder in children: common condition with complex relation and disabling consequences. Epilepsy Behav 32:725CrossRefGoogle Scholar
  61. 61.
    Paolino MC, Ferretti A, Villa MP, Parisi P (2015) Headache and ADHD in pediatric age: possible physiopathological links. Curr Pain Headache Rep 19(7):25CrossRefPubMedGoogle Scholar
  62. 62.
    Parisi P, Verrotti A, Paolino MC, Miano S, Urbano A, Bernabucci M, Villa MP (2010) Cognitive profile, parental education and BMI in children: reflections on common neuroendrocrinobiological roots. Pediatr Endocrinol Metab 23(11):113341Google Scholar
  63. 63.
    Nguyen JCD, Killcross AS, Jenkins TA (2014) Obesity and cognitive decline: role of inflammation and vascular changes. Front Neurosci 8:375. doi: 10.3389/fnins.2014.00375 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wang C, Chan JSY, Ren L, Yan JH (2016) Obesity reduces cognitive and motor functions across the lifespan. Neural Plast 2016:2473081. doi: 10.1155/2016/2473081 PubMedPubMedCentralGoogle Scholar
  65. 65.
    Parisi P, Verrotti A, Paolino MC, Urbano A, Bernabucci M, Castaldo R, Villa MP (2010) Headache and cognitive profile in children: a crosssectional controlled study. J Headache Pain 11(1):4551CrossRefGoogle Scholar
  66. 66.
    Moutran ARC, Villa TR, Diaz LAS, Noffs MHS, Pinto MMP; Gabbai AA; Carvalho DS. Migraine and cognition in children: a controlled study. Arq Neuro Psiquiatr. 2011. doi: 10.1590/S0004-282X2011000200010. (São Paulo)
  67. 67.
    Ozbaran B, Kose S, Yuzuguldu O et al (2015) Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder. World J Biol Psychiatry 16(8):619–624. doi: 10.3109/15622975.2015.1051109 CrossRefPubMedGoogle Scholar
  68. 68.
    Tenore GC, Daglia M, Orlando V et al (2015) Coffee and depression: a short review of literature. Curr Pharm Des 21(34):5034–5040CrossRefPubMedGoogle Scholar
  69. 69.
    Lee MJ, Choi HA, Choi H et al (2016) Caffeine discontinuation improves acute migraine treatment: a prospective clinic-based study. J Headache Pain 17(1):71. doi: 10.1186/s10194-016-0662-5 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Stark JG, Engelking D, McMahen R et al (2016) A randomized crossover study to assess the pharmacokinetics of a novel amphetamine extended-release orally disintegrating tablet in healthy adults. Postgrad Med 128(7):648–655. doi: 10.1080/00325481.2016.1216716 CrossRefPubMedGoogle Scholar
  71. 71.
    Ames D, Carr-Lopez SM, Gutierrez MA et al (2016) Detecting and managing adverse effects of antipsychotic medications: current state of play. Psychiatr Clin N Am 39(2):275–311. doi: 10.1016/j.psc.2016.01.008 CrossRefGoogle Scholar
  72. 72.
    Schrantee A, Tamminga HGH, Bouziane C et al (2016) Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder. JAMA Psychiatry 73(9):955–962. doi: 10.1001/jamapsychiatry.2016.1572 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Schrantee A, Bouziane C, Bron EE et al (2017) Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder. Brain Imaging Behav. doi: 10.1007/s11682-017-9707-x PubMedGoogle Scholar
  74. 74.
    Kral MC, Lally MD, Boan AD (2017) Effectiveness and side effect profile of stimulant medication for the treatment of attention-deficit/hyperactivity disorder in youth with epilepsy. J Child Adolesc Psychopharmacol. doi: 10.1089/cap.2016.0186 PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Haitham Salem
    • 1
  • David Vivas
    • 2
  • Fei Cao
    • 1
  • Iram F. Kazimi
    • 2
  • Antonio L. Teixeira
    • 1
  • Cristian P. Zeni
    • 2
  1. 1.Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolUniversity of Texas Health Science CenterHoustonUSA
  2. 2.Pediatric Mood Disorders/ADHD Across Lifespan Programs, Department of Psychiatry and Behavioral Sciences, McGovern Medical SchoolUniversity of Texas Health Science CenterHoustonUSA

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