Case-Based Review

Treating Migraine in Teenagers

Journal of Clinical Outcomes Management. 2016 January;23(1)

References

1. Tepper SJ, Dahlöf CG, Dowson A, et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache 2004;44:856–64.

2. Lewis DW et al. Practice parameter: evaluation of children and adolescents with recurrent headaches: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2002;59:490–8.

3. Martens D, Oster I, Gottschlling S, et al. Cerebral MRI and EEG studies in the initial management of pediatric headaches. Swiss Med Wkly 2012;142:w13625.

4. Linder SL. Understanding the comprehensive pediatric headache examination. Pediatr Ann 2005;34:442–6.

5. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33:629–808.

6. Senbil N, Gürer YK, Uner C, et al. Sinusitis in children and adolescents with chronic or recurrent headache: a case-control study. J Headache Pain 2008;9:33–6.

7. Gelfand AA, Reider AC, Goadsby PJ. Cranial autonomic symptoms in pediatric migraine are the rule, not the exception. Neurology 2013;81:431–6.

8. Blau JN. Water deprivation: a new migraine precipitant. Headache 2005;45:757–9.

9. Martins IP, Gouveia RG. More on water and migraine. Cephalalgia 2007;27:372–4.

10. Hämäläinen ML, Hoppu K, Valkeila E, et al. Ibuprofen or acetaminophen for the acute treatment of migraine in children: a double-blind, randomized, placebo-controlled, crossover study. Neurology 1997;48:103–7.

11. Lewis DW, Kellsein D, Sahl G, et al. Children’s ibuprofen suspension for the acute treatment of pediatric migraine. Headache 2002;42:780–6.

12. Lipton RB, Golstein J, Baggish JS, et al. Aspirin is efficacious for the treatment of acute migraine. Headache 2005;45:283–92.

13. Linder SL, Mathew NT, Cady RK, et al. Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial. Headache 2008;48:1326–36.

14. Ahonen K, Hämäläinen ML, Eerola M, et al. A randomized trial of rizatriptan in migraine attacks in children. Neurology 2006;67:1135–40.

15. Ho TW, Pearlman E, Lewis D, et al. Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design. Cephalalgia 2012;32:750–65.

16. Winner P, Lewis D, Visser WH, et al. Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study. Headache 2002;42:49–55.

17. Hewitt DJ, Pearlman E, Hämäläinen M, et al. Long-term open-label safety study of rizatriptan acute treatment in pediatric migraineurs. Headache 2013;53:104–17.

18. Derosier FJ, Lewis D, Hershey AD, et al. Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine. Pediatrics 2012;129:e1411–20.

19. McDonald SA, Hershey AD, Pearlman E, et al. Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents. Headache 2011;51:1374-87.

20. Lewis DW, Winner P, Hershey AD, et al. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics 2007;
120:390–6.

21. Linder SL, Dowson AJ. Zolmitriptan provides effective migraine relief in adolescents. Int J Clin Pract 2000;54:466–9.

22. Winner P, Rothner AD, Saper J, et al. A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents. Pediatrics 2000;106:989–97.

23. Rothner AD, Winner P, Nett R, et al. One-year tolerability and efficacy of sumatriptan nasal spray in adolescents with migraine: results of a multicenter, open-label study. Clin Ther 2000;22:1533–46.

24. Ahonen K, Hämäläinen ML, Rantala H, et al. Nasal sumatriptan is effective in treatment of migraine attacks in children: A randomized trial. Neurology 2004;62:883–7.

25. Natarajan S, Jabbour JT, Webster CJ, et al. Long-term tolerability of sumatriptan nasal spray in adolescent patients with migraine. Headache 2004;44:969–77.

26. Winner P, Rothner AD, Wooten JD, et al. Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study. Headache 2006;46:212–22.

27. Hämäläinen ML, Hoppu K, Santavuori P. Sumatriptan for migraine attacks in children: a randomized placebo-controlled study. Do children with migraine respond to oral sumatriptan differently from adults? Neurology 1997;48:1100–3.

28. Fujita M, Sato K, Nishioka H, et al. Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study. Cephalalgia 2014;34:365–75.

29. Winner P, Linder SL, Lipton RB, et al. Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial. Headache 2007;47:511–8.

30. Rothner A. Efficacy and safety of naratriptan tablets in adolescent migraine [abstract]. J Neurol Sci 1997;150:S106.

31. Elkind AH, Wade A, Ishkanian G. Pharmacokinetics of frovatriptan in adolescent migraineurs. J Clin Pharmacol 2004;44:1158–65.

32. Manack AN, Buse DC, Lipton RB. Chronic migraine: epidemiology and disease burden. Curr Pain Headache Rep 2011;15:70–8.

33. Winner P, Pearlman EM, Linder SL, et al. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache 2005;45:1304–12.

34. Lakshmi CV, Singhi P, Malhi P, et al. Topiramate in the prophylaxis of pediatric migraine: a double-blind placebo-controlled trial. J Child Neurol 2007;22:829–35.

35. Lewis D, Winner P, Saper J, et al.Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age. Pediatrics 2009;123:924–34.

36. Hershey AD, Powers SW, Vockell AL, et al. Effectiveness of topiramate in the prevention of childhood headaches. Headache 2002;42:810–8.

37. Campistol J, Campos J, Casas C, et al. Topiramate in the prophylactic treatment of migraine in children. J Child Neurol 2005;20:251–3.

38. Unalp A, Uran N, Oztürk A. Comparison of the effectiveness of topiramate and sodium valproate in pediatric migraine. J Child Neurol 2008;23:1377–81.

39. Cruz MJ, Valencia I, Legido A, et al. Efficacy and tolerability of topiramate in pediatric migraine. Pediatr Neurol 2009;41:167–70.

40. Kim H, Byun SH, Kim JS, et al. Comparison of flunarizine and topiramate for the prophylaxis of pediatric migraines. Eur J Paediatr Neurol 2013;17:45–9.

41. Fallah R, Divanizadeh MS, Karimi M, et al. Topiramate and propranolol for prophylaxis of migraine. Indian J Pediatr 2013;80:920–4.

42. Tonekaboni SH, Ghazavi A, Fayyazi A, et al. Prophylaxis of childhood migraine: topiramate versus propranolol. Iran J Child Neurol 2013;7:9–14.

43. Hershey AD, Powers SW, Coffey CS, et al. Childhood and Adolescent Migraine Prevention (CHAMP) study: a double blinded, placebo controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in prevention of childhood and adolescent migraine. Headache 2013;53:799–816.

44. Hershey AD, Powers SW, Bentti AL, et al. Effectiveness of amitriptyline in the prophylactic management of childhood headaches. Headache 2000;40:539–49.

45. Lewis DW, Diamond S, Scott D, et al. Prophylactic treatment of pediatric migraine. Headache 2004;44:230–7.

46. Caruso JM, Brown WD, Exil G, et al. The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Headache 2000 Sep;40:672–6.

47. Pakalnis A, Greenberg G, Drake ME Jr, et al. Pediatric migraine prophylaxis with divalproex. J Child Neurol 2001;16:731–4.

48. Serdaroglu G, Erhan E, Tekgul H, et al. Sodium valproate prophylaxis in childhood migraine. Headache 2002;42:819–22.

49. Miller GS. Efficacy and safety of levetiracetem in pediatric migraine. Headache 2004;44:238–43.

50. Pakalnis A, Kring D, Meier L. Levetiracetam prophylaxis in pediatric migraine--an open label study. Headache 2007;43:427–30.

51. Pakalnis A, Kring D. Zonisamide prophylaxis in refractory pediatric headache. Headache 2006;46:804–7.

52. Apostol G, Cady RK, Laforet GA, et al. Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study. Headache 2008;48:1012–25.

53. Ludvigsson J. Propranolol used in prophylaxis of migraine in children. Acta Neurol 1974;50:109–15.

54. Forsythe WI, Gillies D, Sills MA. Propanolol (‘Inderal’) in the treatment of childhood migraine. Dev Med Child Neurol 1984;26:737–41.

55. Olness K, MacDonald JT, Uden DL. Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine. Pediatrics 1987;79:593–7.

56. Sorge F, DeSimone R, Marano E, et al. Flunarizine in prophylaxis of childhood migraine. A double-blind, placebo-controlled crossover study. Cephalalgia 1988;8:1–6.

57. Guidetti V, Moscato D, Ottaviano S, et al. Flunarizine and migraine in childhood: an evaluation of endocrine function. Cephalalgia 1987;7:263–6.

58. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and complementary treatments for episodic migraine treatment in adults: Report of the quality standards subcommittee of the American Academy of Neurology and American Headache Society. Neurology 2012; 78:1346–53.

59. Oelkers-Ax R, Leins A, Parzer P, et al. Butterbur root extract and music therapy in the prevention of childhood migraine: an explorative study. Eur J Pain 2008;12:301–13.

60. Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract. Headache 2005;45:196–203.

61. Hershey AD, Powers SW, Vockell AL, et al. Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine. Headache 2007;47:73–80.

62. Slater SK, Nelson TD, Kabbouche MA, et al. A randomized, double-blind, crossover, add-on study of coenzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia 2011; 31: 897–905.

63. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 2003;43:601–10.

64. Castelli S, Meossi C, Domenici R, et al. [Magnesium in the prophylaxis of primary headache and other periodic disorders in children]. Pediatr Med Chir 1993;15:481–8. Italian.

65. Condò M, Posar A, Arbizzani A, et al. Riboflavin prophylaxis in pediatric and adolescent migraine. J Headache Pain 2009;10:361–5.

66. MacLennan SC, Wade FM, Forrest KM, et al. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol 2008;23:1300–4.

67. Bruijn J, Duivenvoorden H, Passchier J, et al. Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial. Cephalalgia 2010;30:1426–34.

68. Robbins L. Precipitating factors in migraine: a retrospective review of 494 patients. Headache 1994;34:214–6.

69. Leviton A, Slack WV, Masek B, et al. A computerized behavioral assessment for children with headaches. Headache 1984;24:182–5.

70. Bruni O, Galli F, Guidetti V. Sleep hygiene and migraine in children and adolescents. Cephalalgia 1999;19 Suppl 25:57–9.

71. Lynch-Jordan AM, Sil S, Peugh J, et al. Differential changes in functional disability and pain intensity over the course of psychological treatment for children with chronic pain. Pain 2014;155:1955–61.

72. Eccleston C, Palermo TM, Williams AC, et al. Psychological therapies for the management of chronic and recurrent pain in children and adolescents. Cochrane Database Syst Rev 2014;5:CD003968.

73. Huguet A, McGrath PJ, Stinson J, et al. Efficacy of psychological treatment for headaches: an overview of systematic reviews and analysis of potential modifiers of treatment efficacy. Clin J Pain 2014;30:353–69.

74. Kropp P, Meyer B, Landgraf M, et al. Headache in children: update on biobehavioral treatments. Neuropediatrics 2013;44:20–4.

75. Kröner-Herwig B. Psychological treatments for pediatric headache. Expert Rev Neurother 2011;11:403–10.

76. Powers SW, Andrasik F. Biobehavioral treatment, disability, and psychological effects of pediatric headache. Pediatr Ann 2005;34:461–5.

77. Hermann C, Blanchard EB. Biofeedback in the treatment of headache and other childhood pain. Appl Psychophysiol Biofeedback 2002;27:143–62.

78. Powers SW, Kashikar-Zuck SM, Hershey AD, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA 2013;310:2622–30.

79. Smitherman TA, Wells RE, Ford SG. Emerging behavioral treatments for migraine. Curr Pain Headache Rep 2015;19:13.

80. Slater SK, O’Brien HL, Hershey AD, et al. Psychiatric comorbidity in pediatric chronic daily headache. Cephalalgia 2012;32: 1116–22.

81. Pavlovic JM, Stewart WF, Bruce CA, et al. Burden of migraine related to menses: results from the AMPP study. J Headache Pain 2015;16:24.

82. MacGregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle. Neurology 2004;63:351–3.

83. Granella F, Sances G, Allais G. Characteristics of menstrual and nonmenstrual attacks in women with menstrually related migraine referred to headache centres. Cephalalgia 2004;24:707–16.

84. Crawford MJ, Lehman L, Slater S, et al. Menstrual migraine in adolescents. Headache 2009;49:341–7.

85. Allais G, Bussone G, De Lorenzo C, et al. Naproxen sodium in short-term prophylaxis of pure menstrual migraine: pathophysiological and clinical considerations. Neurol Sci 2007;28(Suppl 2):S225–8.

86. Silberstein S, Elkind AH, Schreiber C, et al. A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine. Neurology 2004;63:261–9.

87. Brandes JL, Poole A, Kallela M, et al. Short-term frovatriptan for the prevention of difficult-to-treat menstrual migraine attacks. Cephalalgia 2009;29:1133–48.

88. Newman L, Mannix LK, Landy S, et al. Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study. Headache 2001;41:248–56.

89. Mannix LK, Savani N, Landy S, et al. Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies. Headache 2007;47:1037–49.

90. Newman LC, Lipton RB, Lay CL, et al. A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine. Neurology 1998;51:307–9.

91. Tuchman MM, Hee A, Emeribe U, et al. Oral zolmitriptan in the short-term prevention of menstrual migraine: a randomized, placebo-controlled study. CNS Drugs 2008;22:877–86.

92. Marcus DA, Bernstein CD, Sullivan EA, et al. Perimenstrual eletriptan prevents menstrual migraine: an open-label study. Headache 2010;50:551–6.

93. Silberstein S, Patel S. Menstrual migraine: an updated review on hormonal causes, prophylaxis and treatment. Expert Opin Pharmacother 2014;15:2063–70.

94. MacGregor EA. Migraine management during menstruation and menopause. Continuum (Minneap Minn) 2015;21(4 Headache):990–1003.

95. Aegidius K, Zwart JA, Hagen K, et al. Oral contraceptives and increased headache prevalence: The Head-HUNT Study. Neurology 2006;66:349–53.

96. Sulak PJ, Scow RD, Preece C, et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol 2000;95:261–6.

97. LaGuardia KD, Fisher AC, Bainbridge JD, et al. Suppression of estrogen-withdrawal headache with extended transdermal contraception. Fertil Steril 2005;83:1875–7.

98. Sulak P,Willis S, Kuehl T, Coffee A, Clark J. Headaches and oral contraceptives: Impact of eliminating the standard 7-day placebo interval. Headache 2007;47:27–37.

99. De Leo V, Scolaro V, Musacchio MC, et al. Combined oral contraceptives in women with menstrual migraine without aura. Fertil Steril 2011;96:917–20.

100. Calhoun AH. A novel specific prophylaxis for menstrual-associated migraine. South Med J 2004;97:819–22.

101. Coffee AL, Sulak PJ, Hill AJ, et al. Extended cycle combined oral contraceptives and prophylactic frovatriptan during the hormone-free interval in women with menstrual-related migraines. J Womens Health (Larchmt) 2014;23:310–7.

102. Vetvik KG, MacGregor EA, Lundqvist C, et al. Contraceptive-induced amenorrhea leads to reduced migraine frequency in women with menstrual migraine without aura. J Headache Pain 2014;15:30.

103. Sucato GS, Gerschultz KL. Extended cycle hormonal contraception in adolescents. Curr Opin Obstet Gynecol 2005;17:461–5.

104. Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 2010;123:612–24.

105. Bigal ME, Kurth T, Santanello N, et al. Migraine and cardiovascular disease: a population-based study. Neurology 2010;74:628–35.

106. Schurks M, Rist PM, Bigal ME, et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009;339:b3914.

107. Gelfand AA, Fullerton HJ, Jacobson A, et al. Is migraine a risk factor for pediatric stroke? Cephalalgia 2015;35:1252–60.

Less commonly used for intermittent prophylaxis are the shorter-acting triptans, but they have shown some efficacy as well. In one prospective study using oral sumatriptan 25 mg TID for 5 days each cycle starting 2 to 3 days before onset of menses, there seemed to be at least some improvement with sumatriptan in most cycles treated [90].Zolmitriptan was studied in one prospective double-blind placebo-controlled study using 2.5 mg BID or 2.5 mg TID for 7 days total with each cycle and was found to be associated with a significant reduction in headache frequency as compared with placebo [91].There has been one prospective trial using eletriptan 20 mg TID for 6 days total starting 2 days prior to menses, which also showed improvement in headache activity in 55% of patients [92].

Hormonal Contraceptives

In general for adult patients, hormonal contraceptives are not considered first-line treatment for menstrually related migraine. However, in patients who do not respond to other modes of treatment, or who plan to use hormonal contraception for contraceptive purposes, published expert opinions have recommended considering extended or continuous hormonal regimens [93,94].

Estrogen withdrawal during the luteal phase of the monthly cycle has long been speculated to be of importance in the pathophysiology of menstrually related migraine [93]and the relationship between hormonal contraceptives and migraine is complicated. Headache is a commonly reported side effect of combined hormonal contraceptives [95]; however, this effect seems to occur mostly during the hormone-free week [96]. It has been shown that headache occurs less frequently in women using an extended cycle regimen (84 or 168 days) as compared to those using a traditional monthly cyclic regimen [97,98].Studies addressing the use of combined hormonal contraceptives for women specifically with menstrually related migraine are limited. One small prospective randomized study showed improvement in menstrually related migraine in patients treated with a low dose (20 mcg ethinyl E[2]) oral hormonal contraceptive in both a 21/7 cycle and a 24/4 cycle, with more improvement in the group using a 24/4 cycle [99].Another showed improvement in menstrually related migraine in all study patients treated with a low-dose hormonal contraceptive (20 mcg ethinyl estradiol) on a 21/7 regimen, but with additional 0.9 mg conjugated equine estrogen during the placebo week [100].There has been one randomized placebo-controlled double-blind trial in patients with menstrually related migraine using an extended 168 hormonal regimen along with frovatriptan vs. placebo for 5 days during the hormone-free interval. Overall daily headache scores were decreased from pre-study cycles, and the increase in headaches during the hormone-free interval was lower in the frovatriptan group [101].A recent study showed that contraceptive-induced amenorrhea can be beneficial for decreasing migraine frequency in patients with menstrual migraine [102].There have been no studies addressing the use of hormonal contraceptives for migraine management in adolescents.

In adolescents, the decision regarding use of hormonal contraceptives is more complicated. There is less of a chance that adolescent patients, especially younger ones, would be planning to use hormones for contraception so their use may be solely for the purpose of migraine management. However, hormonal contraceptives are commonly used in adolescents for management of other menstrual-related disorders, such as menorrhagia, dysmenorrhea, and endometriosis, and extended cycle and continuous regimens have become more popular with adolescent providers in general [103].The general concern with using hormonal contraceptives in adolescents is that they have potential for longer-term use than adult patients, and the effects of using hormonal contraceptives long term are unknown. The major concerns are for potential interference with expected increase in bone mineral density in adolescents, effects on fertility, and risk for cancer and cardiovascular disease [103].Additionally, specifically in migraine patients, is the concern for increased stroke risk. The increased risk for ischemic stroke in patients with migraine, although more specifically with migraine with aura, is well known [104–106]and migraine has recently been shown to be a risk factor for ischemic stroke in adolescents as well [107]. In adults, the use of hormonal contraceptives in patients with migraine with aura is known to increase the risk of ischemic stroke [106],and this has not been studied in adolescents. Given the various unknowns in the use of hormonal contraceptives in patients with menstrually related migraines, we would not recommend this as first-line treatment. However, similarly to adults, in patients who do not respond to other methods of migraine management, or who seek to use hormonal contraceptives for contraception or for other menstrually related disorders, extended or continuous cycle hormonal contraceptives may be a reasonable option, at the lowest possible estrogen dose. However, migraine with aura should be screened for, and its presence should prompt reconsideration of combined hormonal contraceptive use.