A Randomized Trial of Propranolol versus Sodium Valproate for the Prophylaxis of Migraine in Pediatric Patients
Tóm tắt
Migraine is the most common of the paroxysmal disorders to affect the brain in the pediatric population. Both propranolol and sodium valproate (valproic acid) have been advocated as prophylactic agents for childhood migraine. To compare the efficacy and tolerability of propranolol and sodium valproate in the prevention of migraine in the pediatric population. Sixty-three children (aged 5–15 years) with migraine without aura, as defined by the 2004 International Headache Society (IHS) criteria, were included in this prospective, double-blind clinical trial and were randomly assigned to two groups. Group A (n = 32 patients) received propranolol 3mg/kg/day and group B (n = 31 patients) received sodium valproate 30mg/kg/day, with at least 6 months of follow up. The propranolol dosage was adjusted to 2mg/kg/day and the sodium valproate dosage to 15mg/kg/day, after the first follow-up visit. Participants were evaluated by using a detailed questionnaire that asked about the features of headaches and general health characteristics. The study endpoints were successful treatment for a 4- to 6-month period; 3 months of a persistent unsuccessful or incomplete response to treatment; intolerable side effects; and/or patient non-adherence. All data were analyzed longitudinally by comparing baseline data with data from each follow-up. A total of 60 patients completed the full headache prophylaxis period. The baseline headache frequency was reduced by more than 50% in 83% of propranolol recipients and in 63% of sodium valproate recipients (statistically not significant); the overall reduction of baseline headache frequency per month was better in group A (p = 0.044). The mean headache frequency per month was reduced from 13.86 ± 2.11 to 4.23 ± 3.24 in group A, and from 13.23 ± 2.43 to 5.83 ± 4.04 in group B; the difference between the two groups was statistically significant (p < 0.01). The mean headache duration per week was decreased from 9.9 ± 7.4 hours to 3.2 ± 5.9 hours in group A, and from 9.1 ± 6.9 hours to 3.7 ± 5.0 hours in group B; although there was no statistically significant difference between propranolol and sodium valproate, headache duration was markedly improved with each drug (p < 0.002). Reduction of headache severity by at least one grade was seen in 64% of patients in group A and in 56% in group B, and complete cessation of headache attacks occurred in 14% of patients in group A and 10% in group B (not significant). Minor side effects appeared to be fairly well tolerated by patients in both groups, with no significant difference in side effects between the two groups. This prospective study supports the efficacy of propranolol and sodium valproate as prophylaxis for pediatric migraine without aura, based on IHS criteria. There were no significant differences between these two drugs in all evaluated parameters except for the mean headache frequency per month, which was lower with propranolol than with sodium valproate.
Tài liệu tham khảo
Gladstein J, Holden EW, Peralta L, et al. Diagnoses and symptom patterns in children presenting to a pediatric headache clinic. Headache 1993; 33: 497–500
Gallai V, Sarchielli P, Carboni F, et al. Applicability of the 1988 IHS criteria to headache patients under the age of 18 years attending 21 Italian headache clinics. Headache 1995; 35: 146–53
Winner P, Martinez W, Mate L, et al. Classification of pediatric migraine: proposed revisions to the IHS criteria. Headache 1995; 35: 407–10
Abu-Arefeh I, Russell G. Prevalence of headache and migraine in school children. BMJ 1994; 309: 765–9
Mortimer J, Kay J, Jaron A. Epidemiology of headache and childhood migraine in an urban general practice using ad hoc, Vahlquist and IHS criteria. Dev Med Child Neurol 1992; 34: 1095–101
Raieli V, Raimondo D, Cammalleri R, et al. Migraine headache in adolescents: a student population-based study in Montreal. Cephalalgia 1995; 15: 5–12
Sillanpaa M. Prevalence of headache in prepuberty. Headache 1983; 23: 10–4
Bille B. Migraine in childhood and its prognosis. Cephalalgia 1981; 1: 71–5
Barea LM, Tannhauser M, Rotta NT. An epidemiologic study of headache among children and adolescents of southern Brazil. Cephalalgia 1996; 16: 545–9
Stewart WF, Linet MS, Celantano DD, et al. Age and sex-specific incidence rates of migraine with and without visual aura. Am J Epidemiol 1991; 134: 1111–20
Sillanpaa M. Prevalence of migraine and other headache in Finnish children starting school. Headache 1976 Jan; 15(4): 288–90
Sillanpaa M. Changes in the prevalence of migraine and other headache during the first seven school years. Headache 1983 Jan; 23(1): 15–9
Linet MS, Stewart WF. Migraine headache: epidemiologic perspectives. Epidemiol Rev 1984; 6: 107–39
Lipton RB, Silverstein SD, Stewart WF. An update on epidemiology of migraine. Headache 1994; 34: 319–28
Raieli V, Compagno A, Pandolfi E, et al. Headache: what do children and mothers expect from pediatricians? Headache 2010 Feb; 50(2): 290–300
Brna PM, Dooley JM. Headaches in the pediatric population. Semin Pediatr Neurol 2006 Dec; 13(4): 222–30
Headache in children and adolescents. Am Fam Physician 2002 Feb 15; 65(4): 625–32
Silberstein SD, Goadsby PJ, Lipton RB. Management of migraine: an algorithmic approach. Neurology 2000; 55(9 Suppl. 2): S46–52
Rabkin R, Stables DP, Levin NW, et al. The prophylactic value of propranolol in angina pectoris. Am J Cardiol 1966; 18: 370–83
Kass B, Nestvold K. Propranolol (Inderal) and clonidine (Catapressan) in the prophylactic treatment of migraine: a comparative trial. Acta Neurol Scandinav 1980; 61: 351–6
Stensrud P, Sjaastad O. Comparative trial of Tenormin (atenolol) and Inderal (propranolol) in migraine. Headache 1980; 20: 204–7
Behan PO, Reid M. Propranolol in the treatment of migraine. Clin Trials 1980; 224: 201–4
Diamond S, Kudrow L, Stevens J, et al. Long-term study of propranolol in the treatment of migraine. Headache 1982; 22: 268–71
Diamond S, Medina JL. Double blind study of propranolol for migraine prophylaxis. Headache 1976; 16: 24–7
Borgesen SE. Treatment of migraine with propranolol. Postgrad Med J 1976; 52Suppl. 4: 163–5
Klimek A. Use of propranolol in the treatment of migraine. Neurol Neurochim Pol 1975; 10: 12–5
Nair KG. A pilot study of the value of propranolol in migraine. J Postgrad Med 1975; 21: 111–3
Wideroe TE, Vigander T. Propranolol in the treatment of migraine. BMJ 1974; 2: 699–701
Diener HC, Tfelt-Hansen P, Dahlöf C, et al. Topiramate in migraine prophylaxis; results from a placebo-controlled trial with propranolol as an active control. J Neurol 2004; 251(8): 943–50
Taghdiri MM, Razavi Z. A comparison between the treatment and side effect of sodium valproate and propranolol in preventing migraine headaches [poster]. Cephalalgia 2008; 28(4): 466
Pascual J, Leira R, Lainez JM. Combined therapy for migraine prevention? Clinical experience with a [beta]-blocker plus sodium valproate in 52 resistant migraine patients. Cephalalgia 2003; 23(10): 961–2
Ludvigsson J. Propranolol used in prophylaxis of migraine in children. Acta Neurol Scand 1974; 50(1): 109–15
Forsythe WI, Gillies D, Sills MA. Propranolol (‘Inderal’) in the treatment of childhood migraine. Dev Med Child Neurol 1984; 26(6): 373–41
Olness K, MacDonald JT, Uden DL. Comparison of self-hypnosis and propranolol in the treatment of juvenile classic migraine. Pediatrics 1987; 79(4): 593–7
Rompel H, Bauermeister PW. Aetiology of migraine and prevention with carbamazepine (Tegretol): result of a double-blind, cross-over study. S Afr Med J 1970; 44: 75–80
Sorensen KV. Valproate: a new drug in migraine prophylaxis. Acta Neurol Scand 1988; 78(4): 346–8
Chronicle EP, Mulleners WM. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev 2004; (3): CD003226
Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 2004 Apr; 61(4): 490–5
Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004 Feb 25; 291(8): 965–73
Winner P, Pearlman EM, Linder SL. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache 2005 Nov–Dec; 45(10): 1304–12
Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001 Feb; 41(2): 119–28
Steiner TJ, Findley LJ, Yuen AW. Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia 1997 Apr; 17(2): 109–12
Pakalnis A, Kring D, Meier L. Levetiracetam prophylaxis in pediatric migraine: an open-label study. Headache 2007 Mar; 47(3): 427–30
Bakola E, Skapinakis P, Tzoufi M, et al. Anticonvulsant drugs for pediatric migraine prevention: an evidence-based review. Eur J Pain 2009 Oct; 13(9): 893–901
Mathew NT. Antiepileptic drugs in migraine prevention. Headache 2001 Nov–Dec; 41Suppl 1: S18–24
Cuvellier JC, Riquet A, Vallée L. Antiepileptic drugs in pediatric migraine [in French]. Arch Pediatr 2008 Nov; 15(11): 1693–9
Bakola E, Skapinakis P, Tzoufi M, et al. Anticonvulsant drugs for pediatric prevention: an evidence-based review. Eur J Pain 2009 Oct; 13(9): 893–901
D’Amico D. Antiepileptic drugs in the prophylaxis of migraine, chronic headache forms and cluster headache: a review of their efficacy and tolerability. Neurol Sci 2007 May; 28Suppl 2: S188–97
Young WB, Siow HC, Silberstein SD. Anticonvulsants in migraine. Curr Pain Headache Rep 2004 Jun; 8(3): 244–50
Wasiewski WW. Preventive therapy in pediatric migraine. J Child Neurol 2001; 16: 71–8
Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders. 2nd ed. Cephalalgia 2004; 24Suppl. 1: 23–160
Lewis DW. Toward the definition of childhood migraine. Curr Opin Pediatrics 2004; 16: 628–36
Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia 2002; 22: 491–512
Koella WP. CNS-related (side-) effects of β-blockers with special reference to mechanism of action. Eur J Clin Pharmacol 1985; 28: 55–63
Ablad B, Dahlof C. Migraine and β-blockade: modulation of sympathetic neurotransmission. Cephalagia 1986; 6: 7–13
Holroyd KA, Pen Zien DB, Cordingley GE. Propranolol in the management of recurrent migraine a meta-analytic review. Headache 1991; 31: 333–40
Kozubski W, Prusinsk A. Sodium valproate versus propranolol in the prophylatic treatment of migraine. Neurol Neurochir Pol 1995; 29(6): 937–47
Kaniecki RG. A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Arch Neurol 1997; 54(9): 1141–5
Lai FM, Tanikella T, Cervoni P. Effect of gamma-aminobutyric acid (GABA) on vasodilatation in resistance-sized arteries isolated from monkey, rabbit and rat. J Cardiovasc Pharmacol 1988; 12: 372–6
Curter FM, Limmorth V, Moskowitz MA. Possible mechanisms of valproate in migraine prophylaxis. Cephalgia 1997; 17: 93–100
Raskin NH. Acute and prophylactic treatment of migraine: practical approaches and pharmacologic rationale. Neurology 1993; 43Suppl. 3: S39–42
Giesler GJ, Gebhart KD, Yezierski RP, et al. Postsynaptic inhibition of primate spinothalamic neurons by stimulation in nucleus raphe magnus. Brain Res 1981; 204: 184–8
Jordan LM, Kenshalo DR, Martin RF, et al. Depression of primate spinothalamic tract neurons by ionophoretic application of 5-hydro-xytryptamine. Pain 1978; 5: 135–42
Horrobin DF. Prevention of migraine by reducing prolactin levels. Lancet 1973 Apr 7; 301(7806): 777
Murialdo G, Polleri A. Prolactin and migraine. Headache 1987; 27: 278–9
Rimmer EM, Richen SA. An update on sodium valproate. Pharmacotherapy 1985; 5: 171–84
Chapman A, Keane PE, Meldrum BS. Mechanisms of anticonvulsant action of valproate. Prog Neurobiol 1982; 19: 315–9
Fediani F, Cominelli F, Sgarzi M. Anticonvulsant drugs in migraine prophylaxis. J Headache Pain 2001; 2: 121–4
Bigal EM, Lipton RB, Krymchantowski VA. The medical management of migraine. Am J Ther 2004; 11: 130–40
Serdaroglu G, Erhan E, Tekgul H, et al. Sodium valproate prophylaxis in childhood migraine. Headache 2002; 42(8): 819–22
Mathew NT, Saperj R, Silberstein SD, et al. Migraine prophylaxis with divalproex. Arch Neurol 1995; 52(3): 281–6
Pakalnis A, Greenberg G, Drake ME, et al. Pediatric migraine prophylaxis with divalproex. J Child Neurol 2001; 16: 731–4
Freitag FG, Collins SD, Carlson BA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology 2002; 58: 1652–9
Hering R, Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 1992; 12: 81–4
Silberstein SD, Saper JR, Mathew NT. The safety and efficacy of divalproex sodium in the prophylaxis of migraine headache: a multicenter, double-blind placebo-controlled study. Headache 1993; 33: 264–5
Klapper J. Divalproex sodium in migraine prophylaxis: a dose controlled study. Cephalalgia 1997; 17: 103–8
Erdemoglu AK, Ozbakir S. Valproic acid in prophylaxis of refractory migraine. Acta Neurol Scand 2000; 102: 354–8
Coria F, Sempere AP, Duarte J, et al. Low-dose sodium valproate in the prophylaxis of migraine. Clin Neuropharmacol 1994; 17: 569–73
Caruso JM, Brown WD, Exil G, et al. The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Headache 2000; 40(8): 672–6
Bromfield EB, Dworetzky BA, Wyszynski DF, et al. Valproate teratogenicity and epilepsy syndrome. Epilepsia 2008; 49(12): 2122–4
Alsdorf R, Wyszynski DF. Teratogenicity of sodium valproate. Expert Opin Drug Saf 2005; 4(2): 345–53
Hershey AD, Powers SW, Vockell A, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children