A Randomized Trial of Propranolol versus Sodium Valproate for the Prophylaxis of Migraine in Pediatric Patients
ABSTRACT 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 3 mg/kg/day and group B (n = 31 patients) received sodium valproate 30 mg/kg/day, with at least 6 months of follow up. The propranolol dosage was adjusted to 2 mg/kg/day and the sodium valproate dosage to 15 mg/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.
- SourceAvailable from: Olga Lyubashina
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- "Valproate—a highly potent anticonvulsant, successfully used for prophylactics (Bidabadi and Mashouf, 2010; Corbo, 2003; D'Amico, 2010; Freitag, 2003; Lovell and Marmura, 2010; Mathew, 2001) and abortive migraine treatments (Edwards et al., 2001; Leniger et al., 2005; Mathew et al., 2000; Shahien et al., 2011; Stillman et al., 2004)—also exhibits similar properties. Experiments on rats demonstrated that microiontophoretically applied valproate inhibited the VPM neuronal responses to both superior sagittal sinus electrical stimulation and intrathalamic ejection of L-glutamate (Andreou et al., 2010). "
ABSTRACT: Valproate is widely used for migraine treatments, although precise mechanisms of its anticephalgic action are poorly understood. Migraine attacks are thought to occur due to trigemino-vascular system activation, which in turn, stimulates nociceptive transmission in trigemino-thalamo-cortical pathway. The ventroposteromedial (VPM) nucleus of the thalamus is considered to play a prominent role in neurobiology of headaches by serving as the highest subcortical relay for conveying nociceptive information from intra- and extracranial structures to the cortex. While it has been demonstrated that valproate can modulate trigemino-vascular nociceptive neurotransmission in the VPM, its effects have been investigated using only intrathalamic ejection of the compound in pentobarbitone sodium anesthetized rats. The objective of our study was to evaluate the effects of intravenously administered valproate on both ongoing firing of the VPM neurons and their activity induced by electrical stimulation of the dura mater. The experiments were performed on rats under nonbarbiturate anesthesia. To define the dose-dependent properties and longevity of the studied effects of valproate, two distinguished dosing regiments were used: bolus (single infusion at a dose of 300mg/kg) and cumulative (thrice-repeated administration of 100mg/kg performed 30min apart). Intravenous administration of valproate produced the dose-dependent suppression of both the ongoing activity of the thalamic VPM neurons and their responses to electrical stimulation of the dura mater. This effect was fast-developing (within 5min) and short-lasting (no longer than 30min). These data suggest that intravenous administration of valproate could produce a reduction of the thalamo-cortical nociceptive transmission associated with trigemino-vascular activation.European journal of pharmacology 05/2013; 715(1-3). DOI:10.1016/j.ejphar.2013.05.019 · 2.53 Impact Factor
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ABSTRACT: For the last thirty years ocean bottom seismometers (OBSs) have been used to survey the oceans. However, the quality of the data they produce is often degraded due to poor coupling or high levels of ambient noise. In contrast, sensors placed beneath the seafloor avoid many of these problems. For the last two decades burials have relied on Ocean Drilling Program (ODP) boreholes. This approach is expensive and demands numerous human resources. In addition, the locations of these boreholes, determined by the ODP, are rarely desirable for monitoring seismic activity. In this paper a sub-bottom seismic acquisition system is presented that uses free-fall devices, or deep ocean seismic penetrators (DOSP), to place sensors several tens of metres beneath the seafloor. The DOSPs weigh approximately 1800 kg, achieve terminal velocities between 30-50 m/s and penetrate to depths of 20-30 metres in soft sea sediments. Once buried, they record seismic activity and transmit data back to the surface using a frequency shift keyed (FSK) modulation technique. The results of an experiment conducted in the Mediterranean using this system are presented. These confirm the predicted dynamic and kinematic behaviour of the DOSP and allow an assessment of the ambient seismic noise level at a depth of ≈30 metres beneath the seafloor. In conclusion this paper discusses the potential use of free-fall devices to increase our understanding of processes in the deep oceans, with particular emphasis on their applicability to future deep ocean seismologyOCEANS '97. MTS/IEEE Conference Proceedings; 11/1997
Article: Pediatric Headache[Show abstract] [Hide abstract]
ABSTRACT: Headache is a common presenting complaint in the practice of child neurology. The medical and social impact of headache is often very severe both for the affected child and for his/her family. As there exist few good clinical studies to guide practitioners in choosing appropriate medications, treatments are mostly based on extrapolation of adult study results. Personal trial-and-error experience and specialized considerations for patients also influence choice and implementation. A careful medical history, however, can enable optimal choices for abortive and prophylactic use in the context of a multi-disciplinary approach toward headache management. This article provides a pathophysiologically-based overview of a wide range of therapeutic options for children and adolescents with headache.Seminars in pediatric neurology 12/2010; 17(4):224-9. DOI:10.1016/j.spen.2010.10.004 · 2.23 Impact Factor