Approximately 25% of children will be migraine- free by the age of 25, boys in a significantly higher percentage than girls and more than half will still have headaches at the age of 50. The most common symptoms include episodic attacks of moderate to very severe headache (typically throbbing, unilateral, and exacerbated by physical activity), accompanied by nausea, photophobia and phonophobia. Attacks are heterogeneous in symptomatology, severity and disability, both between different individuals and separate attacks in the same individual sufferer. Migraine is a highly disabling condition that leads to reduced quality of life among children.
Ketorolac is another NSAID used mostly in the emergency department. At this time we only have one study regarding the use of ketorolac in pediatric patients suffering from migraine at the emergency room. It was used an intravenous formula, starting from 0.5 mg/kg to a maximum of 30 mg/dose. Ketorolac was effective in 55.2 % of the patients in one hour. An oral formula is also available for home treatment with a dosage of 0.75 mg/kg (6).
triptan therapy in migraine pdf 11
Triptans are a class of tryptamine-based pharmacological agents which act as serotonin agonists, helping reduce cerebral blood flow and neuropeptide release. Sumatriptan is considered to be the reference standard and it is available with different preparations including oral, intranasal, and subcutaneous forms. In the pediatric population the effect of oral sumatriptan showed no significant pain relief (7).
Other triptans approved by the FDA for treating migraine attacks in pediatric population, children above the age of 6 and adolescents, are almotriptan, zolmitriptan and rizatriptan. Although limited, studies among the children suffering from migraine attacks show that rizatriptan provided statistically significant pain relief at 2 hours while also reducing associated nausea and vomiting.
Zolmitriptan, in both nasal and oral administration, has proved to be effective in the adolescent population. Also, forvatriptan might have the same effect in adolescents as in adults, using comparable doses (7,8).
Valproate treatment starts with a dose of 10 to 15 mg/kg divided in two daily doses. This dose can be increased with 15 mg/kg increments reaching a maximum of 60 mg/kg/day. The therapeutic dose for treating migraine is not yet established, but the therapeutic range is considered to be 50 to 100 mg/dL. If given a dose that exceeds 150 mg/dL, the patient should be monitored closely.
Newer antiepileptic drugs such as topiramate, gabapentin and levetiracetam have been shown to reduce headache frequency in openlabel, retrospective trials. Topiramate is, generally, a well-tolerated therapy. In migraneur children the treatment starts at 15 mg/day and it is increased during a period of over eight weeks to 2 to 3 mg/kg daily. The maximum tolerated dose may reach a limit of 200 mg/day. Topiramate treatment may cause anorexia, weight loss, gastroenteritis, as well as concentration difficulty, somnolence or even cognitive impairment. Given the low dose administrated in treating migraine, Topiramat can be a good choice for the pediatric population due to its efficacy and the low frequency of side effects (13).
An important part of the prophylactic treatment in pediatric migraine is the psychological support that should be given to each child in order to have a compliant patient without any further emotional disorders that may arise from both the pressure of the daily treatment as well as the vulnerability and emotional fragility that characterize these particular age categories. It is not to be forgotten the need of a multidisciplinary team (pediatric neurologist, pediatrician, psychologist, support groups, family) when treating a migraineur child.
This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg).
The 3-mg SC dose of sumatriptan in DFN-11 provided relief of migraine pain and associated symptoms comparable to a 6-mg SC dose of sumatriptan. Tolerability was similar with both study medications; DFN-11 treatment was associated with fewer triptan sensations than the 6-mg dose. DFN-11, with its 3-mg dose of sumatriptan, may be a clinically useful alternative to higher-dose autoinjectors.
Despite its well-established efficacy and rapid onset of action, sumatriptan 6 mg SC injection has a suboptimal tolerability profile. Many patients (42%) experience triptan sensations [13], such as paresthesia and chest symptoms, that appear to be dose-related [14]. Concerns about drug-related adverse events (AEs), which have caused two thirds of migraine patients to delay or avoid taking a prescription medication, may help to explain why fewer than 10% of eligible migraine patients use the SC formulation of sumatriptan to treat their disease [15]. These concerns can be particularly important in patients with various types of medical conditions (eg, cardiovascular and cerebrovascular disease and some psychiatric illnesses) and/or treated with various medications (eg, monoamine oxidase inhibitors and selective serotonin reuptake inhibitors) [9]. Based on previous research [16], we hypothesized that a formulation using a lower doses of sumatriptan may improve safety and tolerability while maintaining efficacy similar to 6 mg SC sumatriptan, and that a 3-mg dose may be sufficient in many patients. The objective of this exploratory study was to compare the efficacy and tolerability of 3 mg SC sumatriptan (using DFN-11 and matching placebo autoinjectors consecutively) with 6 mg SC sumatriptan (using 2 DFN-11 autoinjectors consecutively) for the acute treatment of episodic migraine attacks.
This was a double-blind, crossover, pilot study conducted at a single study center (Clinvest; Springfield, MO). The study compared a 3-mg SC dose of sumatriptan with the commonly prescribed 6-mg SC dose in 19 subjects. The protocol was approved by the Sterling Institutional Review Board, and the study was conducted in compliance with good clinical practice and in accordance with the ethical principles set forth in the Declaration of Helsinki. Prior to the initiation of any study-specific procedures, investigators explained the nature of the study to the subjects, and subjects provided informed consent. The first subject was enrolled on 15 September 2015, and the study was completed on 14 April 2016. Additional information about this trial is available online at ClinicalTrials.gov (Identifier: NCT02571049).
The study consisted of 4 visits: screening, randomization, treatment crossover, and end-of-study. Subjects treated up to 2 attacks within 4 weeks. At the screening visit, subjects provided a detailed medical and headache/migraine history, a physical examination was performed, laboratory assessment samples (ie, hematology, serum chemistry, urine analysis, serology, urine drug screen) were obtained, inclusion/exclusion criteria were verified, and a 12-lead electrocardiogram (ECG) was completed. Eligible subjects returned to the site with 14 days of the screening visit and were trained in the appropriate use of the autoinjector device and given printed instructions to take home that reinforced correct DFN-11 administration.
Subjects were divided into 1 block and randomized (1:1) to receive 3 mg SC sumatriptan (using DFN-11 and matching placebo autoinjectors consecutively) or 6 mg SC sumatriptan (using 2 DFN-11 autoinjectors consecutively) in a crossover design and were dispensed the first treatment in the sequence. The randomization scheme was generated by study personnel with no subject interaction or other monitoring roles using an online tool ( ); it was provided to the drug packing company, which used it to prepare and pre-label the kits with sequential numbers. The research coordinator was instructed to dispense the lowest kit number available.
Tolerability was assessed by comparing AEs occurring up to 24 h postdose. Safety measures included AEs, physical examinations, vital signs, ECG readings, and laboratory assessments (hematology, serum chemistry, urine analysis). Adverse events were coded with the Medical Dictionary for Regulatory Activities (MedDRA, version 17.0) and classified by date of onset, duration, frequency, severity, and relationship to study medication. The classification of AEs as triptan sensations was determined by principal investigator. Spontaneously reported AEs were recorded for up to 5 days after the last dose of study drug; AEs determined as serious were recorded for up to 30 days.
Twenty-four subjects were screened, 20 subjects were randomized (1 never treated), and 19 subjects treated at least 1 migraine attack (Fig. 1). The study population was 80% female and 95% Caucasian, with a mean age of 39.8 years. At baseline, subjects were experiencing 5 migraine days and 6.8 headache days per month on average (Table 2).
The most common AEs were triptan sensations known to be associated with SC triptan usage; all were mild to moderate and similar in frequency and severity to those seen in previous studies of the SC formulation of sumatriptan. Notably, while most subjects experienced symptoms with both sumatriptan doses, fewer subjects had triptan sensations only after treatment with the 3-mg dose than with the 6-mg dose. In addition, the triptan sensation of chest pain, which has been shown to cause up to 10% of sumatriptan-treated patients to discontinue therapy [21] and may lead to substantially increased medical costs for migraine care [22], was not observed after the 3-mg dose of DFN-11 treatment. With the 6 mg SC sumatriptan treatment, 10% of subjects were affected, and the mean duration of the events exceeded 6 h. The implications of these findings deserve to be explored in future research. 2ff7e9595c
Comments