Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis

Abstract

IMPORTANCE Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.OBJECTIVE To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.DATA SOURCES Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.STUDY SELECTION Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. DATA EXTRACTION AND SYNTHESIS Data extraction was conducted according to PreferredReporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. MAIN OUTCOMES AND MEASURESPrimary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).RESULTS Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. CONCLUSIONS AND RELEVANCEProphylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

Epidemiology of Headache in Children and Adolescents—Another Type of Pandemia

“…Nevertheless, prophylactic drugs in young migraine patients such as flunarizine, metoprolol, amitriptyline, topiramate should be considered, if all non-medication therapies do not decrease the migraine frequency and individual disease load is high. Importantly, when using these drugs information and education of the patient and of the parents is needed as well as a close clinical follow-up [ 46 , 47 ]. Magnesium as nutritional supplement represents an alternative prophylactic, which should be used 10 mg/kg/BW per day.…”

Talking to Children and Families about Chronic Pain: The Importance of Pain Education—An Introduction for Pediatricians and Other Health Care Providers

“…However, current knowledge of treatment approaches is often based on data extrapolated from adults [ 19 , 20 ]. This is particularly problematic for pharmacological treatments, since there is limited evidence that supports their efficacy and safety [ 20 , 21 ] in pediatric patients with chronic pain. In terms of non-pharmacological interventions, psychological therapies usually include multicomponent cognitive behavioral therapy, relaxation-based content, and/or problem-solving strategies.…”

“…Specifically, research in the field of placebo sheds light on the impact of contextual factors, this is because placebos by definition have no pharmacological ingredients or specific factors, respectively. Relevant placebo effects have been reported in a variety of pediatric conditions including depression and anxiety [ 48 , 49 ], autism [ 50 ], attention-deficit/hyperactivity disorder [ 51 ], migraine [ 21 , 52 ] and acute pain [ 53 ]. Adult placebo studies highlight the importance of a positive patient-health care provider relationship: a sample of patients suffering from irritable bowel syndrome were placed on a waiting list, given placebo acupuncture alone (using a sham acupuncture device), or placebo acupuncture augmented by warmth, confidence, and attention from the health care provider [ 54 ].…”

Effectiveness of chiropractic manipulation versus sham manipulation for recurrent headaches in children aged 7-14 years. A randomised clinical trial

“…Considering the signi cant consequences of paediatric headache and the lack of effective and safe pharmacological treatment (1,3,38), non-pharmacological treatments such as spinal manipulation could be attractive alternatives (45). The positive results from this study combined with the low risk of adverse events should encourage clinicians and policy-makers to consider spinal manipulation for children with recurrent headaches.…”