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Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine ProphylaxisA Systematic Review and Network Meta-analysis

Educational Objective
To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.
1 Credit CME
Key Points

Question  What are the most effective, safe, and accepted pharmacologic treatments for migraine prophylaxis in children and adolescents?

Findings  In this network meta-analysis, comparing head-to-head and placebo-controlled trials found no significant long-term effects for migraine prophylaxis relative to placebo. Medium-sized short-term effects were found for propranolol and topiramate, but the prediction interval indicates that significant beneficial effects are to be expected in only 70% of similar studies conducted in the future.

Meaning  Considering the limited effect size, a cautious, individual, and tailored treatment approach to migraine prophylaxis is of great importance.


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 Preferred Reporting 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 Measures  Primary 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 Relevance  Prophylactic 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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Joe Kossowsky, PhD, MMSc, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, 333 Longwood Ave, Boston, MA 02115 (joe.kossowsky@childrens.harvard.edu).

Accepted for Publication: September 25, 2019.

Published Online: February 10, 2020. doi:10.1001/jamapediatrics.2019.5856

Author Contributions: Drs Kossowsky and Meissner had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Locher and Kossowsky contributed equally to this study.

Concept and design: Locher, Kossowsky, Linde, Meissner.

Acquisition, analysis, or interpretation of data: Locher, Kossowsky, Koechlin, Lam, Barthel, Berde, Gaab, Schwarzer, Meissner.

Drafting of the manuscript: Locher, Kossowsky, Koechlin, Meissner.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Locher, Kossowsky, Koechlin, Berde, Schwarzer.

Obtained funding: Locher, Meissner.

Administrative, technical, or material support: Locher, Kossowsky, Barthel, Gaab.

Supervision: Locher, Kossowsky, Berde, Gaab, Linde, Meissner.

Conflict of Interest Disclosures: Dr Berde reports grants from Amgen and other support from Grunenthal and Akelos outside the submitted work. Dr Locher reported grants from Swiss National Science Foundation during the conduct of the study. Dr Meissner reported grants from Schweizer-Arau Foundation, Germany, during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported in part by the Sara Page Mayo Endowment for Pediatric Pain Research, Education, and Treatment. Dr Locher received funding for this project from the Swiss National Science Foundation (P400PS_180730). Dr Meissner received funding from the Schweizer-Arau-Foundation and the Theophrastus Foundation, Germany.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Abu-Arafeh  I, Razak  S, Sivaraman  B, Graham  C.  Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies.  Dev Med Child Neurol. 2010;52(12):1088-1097. doi:10.1111/j.1469-8749.2010.03793.xPubMedGoogle ScholarCrossref
Stewart  WF, Lipton  RB, Celentano  DD, Reed  ML.  Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors.  JAMA. 1992;267(1):64-69. doi:10.1001/jama.1992.03480010072027PubMedGoogle ScholarCrossref
Burch  RC, Loder  S, Loder  E, Smitherman  TA.  The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies.  Headache. 2015;55(1):21-34. doi:10.1111/head.12482PubMedGoogle ScholarCrossref
Powers  SW, Patton  SR, Hommel  KA, Hershey  AD.  Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses.  Pediatrics. 2003;112(1 Pt 1):e1-e5. doi:10.1542/peds.112.1.e1PubMedGoogle ScholarCrossref
National Headache Foundation. FDA approves treximet for adolescents. https://headaches.org/2015/06/26/fda-approves-treximet-for-adolescents/. Accessed June 6, 2019.
Lai  LL, Koh  L, Ho  JA, Ting  A, Obi  A.  Off-label prescribing for children with migraines in US ambulatory care settings.  J Manag Care Spec Pharm. 2017;23(3):382-387. doi:10.18553/jmcp.2017.23.3.382PubMedGoogle Scholar
Richer  L, Billinghurst  L, Linsdell  MA,  et al.  Drugs for the acute treatment of migraine in children and adolescents.  Cochrane Database Syst Rev. 2016;4:CD005220. doi:10.1002/14651858.CD005220.pub2PubMedGoogle Scholar
Winner  P, Linder  S, Hershey  AD.  Consistency of response to sumatriptan/naproxen sodium in a randomized placebo-controlled, cross-over study for the acute treatment of migraine in adolescence.  Headache. 2015;55(4):519-528. doi:10.1111/head.12555PubMedGoogle ScholarCrossref
Sun  H, Bastings  E, Temeck  J,  et al.  Migraine therapeutics in adolescents: a systematic analysis and historic perspectives of triptan trials in adolescents.  JAMA Pediatr. 2013;167(3):243-249. doi:10.1001/jamapediatrics.2013.872PubMedGoogle ScholarCrossref
El-Chammas  K, Keyes  J, Thompson  N, Vijayakumar  J, Becher  D, Jackson  JL.  Pharmacologic treatment of pediatric headaches: a meta-analysis.  JAMA Pediatr. 2013;167(3):250-258. doi:10.1001/jamapediatrics.2013.508PubMedGoogle ScholarCrossref
Le  K, Yu  D, Wang  J, Ali  AI, Guo  Y.  Is topiramate effective for migraine prevention in patients less than 18 years of age? a meta-analysis of randomized controlled trials.  J Headache Pain. 2017;18(1):69. doi:10.1186/s10194-017-0776-4PubMedGoogle ScholarCrossref
Shamliyan  TA, Kane  RL, Ramakrishnan  R,  et al. Migraine in children: preventive pharmacologic treatments. https://www.ncbi.nlm.nih.gov/books/NBK148703/. Published 2013. Accessed June 6, 2019.
Powers  SW, Coffey  CS, Chamberlin  LA,  et al; CHAMP Investigators.  Trial of amitriptyline, topiramate, and placebo for pediatric migraine.  N Engl J Med. 2017;376(2):115-124. doi:10.1056/NEJMoa1610384PubMedGoogle ScholarCrossref
Liberati  A, Altman  DG, Tetzlaff  J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.  BMJ. 2009;339:b2700. doi:10.1136/bmj.b2700PubMedGoogle ScholarCrossref
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG, Group  P; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097PubMedGoogle Scholar
Meissner  K, Fässler  M, Rücker  G,  et al.  Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis.  JAMA Intern Med. 2013;173(21):1941-1951. doi:10.1001/jamainternmed.2013.10391PubMedGoogle ScholarCrossref
Lipsey  MW, Wilson  DB.  Practical Meta-Analysis. Thousand Oaks, CA: Sage; 2001.
Higgins  JPT, Deeks  JJ. Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. http://www.handbook.cochrane.org. Published March 2011. Accessed January 2, 2020.
Higgins  JPT, Deeks  JJ, Altman  DG. Chapter 16: Special topics in statistics. In: Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. http://www.handbook.cochrane.org. Published March 2011. Accessed January 2, 2020.
Winner  P, Pearlman  EM, Linder  SL, Jordan  DM, Fisher  AC, Hulihan  J; Topiramate Pediatric Migraine Study Investigators.  Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial.  Headache. 2005;45(10):1304-1312. doi:10.1111/j.1526-4610.2005.00262.xPubMedGoogle ScholarCrossref
Rücker  G, Cates  CJ, Schwarzer  G.  Methods for including information from multi-arm trials in pairwise meta-analysis.  Res Synth Methods. 2017;8(4):392-403. doi:10.1002/jrsm.1259PubMedGoogle ScholarCrossref
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(7):1012-1025. doi:10.1111/j.1526-4610.2008.01081.xPubMedGoogle ScholarCrossref
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(3):924-934. doi:10.1542/peds.2008-0642PubMedGoogle ScholarCrossref
Talebian  A, Soltani  B, Banafshe  HR, Moosavi  GA, Talebian  M, Soltani  S.  Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial.  Electron Physician. 2018;10(2):6279-6285. doi:10.19082/6279PubMedGoogle ScholarCrossref
Higgins  JPT, Altman  DG, Sterne  JAC. Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. http://www.handbook.cochrane.org. Published March 2011. Accessed January 2, 2020.
Cohen  J.  Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.
Deeks  JJ, Higgins  JPT, Altman  DG. Chapter 9: Analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. http://www.handbook.cochrane.org. Published March 2011. Accessed January 2, 2020.
Moncrieff  J, Kirsch  I.  Efficacy of antidepressants in adults.  BMJ. 2005;331(7509):155-157. doi:10.1136/bmj.331.7509.155PubMedGoogle ScholarCrossref
Altman  DG, Royston  P.  The cost of dichotomising continuous variables.  BMJ. 2006;332(7549):1080. doi:10.1136/bmj.332.7549.1080PubMedGoogle ScholarCrossref
Cipriani  A, Furukawa  TA, Salanti  G,  et al.  Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.  Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7PubMedGoogle ScholarCrossref
Borenstein  M, Hedges  LV, Higgins  JPT, Rothstein  HR.  Introduction to Meta-Analysis. Hoboken, NJ: John Wiley & Sons; 2011.
netmeta: Network Meta-Analysis using Frequentist Methods. [computer program]. https://github.com/guido-s/netmeta2019. Accessed January 2, 2020.
Rücker  G.  Network meta-analysis, electrical networks and graph theory.  Res Synth Methods. 2012;3(4):312-324. doi:10.1002/jrsm.1058PubMedGoogle ScholarCrossref
Salanti  G, Ades  AE, Ioannidis  JP.  Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.  J Clin Epidemiol. 2011;64(2):163-171. doi:10.1016/j.jclinepi.2010.03.016PubMedGoogle ScholarCrossref
Rücker  G, Schwarzer  G.  Resolve conflicting rankings of outcomes in network meta-analysis: partial ordering of treatments.  Res Synth Methods. 2017;8(4):526-536. doi:10.1002/jrsm.1270PubMedGoogle ScholarCrossref
Cochran  WG.  The comparison of percentages in matched samples.  Biometrika. 1950;37(3-4):256-266. doi:10.1093/biomet/37.3-4.256PubMedGoogle ScholarCrossref
Higgins  JPT, Thompson  SG, Deeks  JJ, Altman  DG.  Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560. doi:10.1136/bmj.327.7414.557PubMedGoogle ScholarCrossref
Efthimiou  O, Debray  TP, van Valkenhoef  G,  et al; GetReal Methods Review Group.  GetReal in network meta-analysis: a review of the methodology.  Res Synth Methods. 2016;7(3):236-263. doi:10.1002/jrsm.1195PubMedGoogle ScholarCrossref
Salanti  G.  Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool.  Res Synth Methods. 2012;3(2):80-97. doi:10.1002/jrsm.1037PubMedGoogle ScholarCrossref
Linde  K, Rücker  G, Schneider  A, Kriston  L.  Questionable assumptions hampered interpretation of a network meta-analysis of primary care depression treatments.  J Clin Epidemiol. 2016;71:86-96. doi:10.1016/j.jclinepi.2015.10.010PubMedGoogle ScholarCrossref
Dias  S, Welton  NJ, Caldwell  DM, Ades  AE.  Checking consistency in mixed treatment comparison meta-analysis.  Stat Med. 2010;29(7-8):932-944. doi:10.1002/sim.3767PubMedGoogle ScholarCrossref
Higgins  JP, Jackson  D, Barrett  JK, Lu  G, Ades  AE, White  IR.  Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies.  Res Synth Methods. 2012;3(2):98-110. doi:10.1002/jrsm.1044PubMedGoogle ScholarCrossref
Salanti  G, Del Giovane  C, Chaimani  A, Caldwell  DM, Higgins  JP.  Evaluating the quality of evidence from a network meta-analysis.  PLoS One. 2014;9(7):e99682. doi:10.1371/journal.pone.0099682PubMedGoogle Scholar
CINeMA: Confidence in Network Meta-Analysis, version 1.4.1 [computer program]. http://cinema.ispm.ch/. Published 2017. Accessed June 6, 2019.
IntHout  J, Ioannidis  JP, Rovers  MM, Goeman  JJ.  Plea for routinely presenting prediction intervals in meta-analysis.  BMJ Open. 2016;6(7):e010247. doi:10.1136/bmjopen-2015-010247PubMedGoogle Scholar
Chaimani  A, Salanti  G.  Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions.  Res Synth Methods. 2012;3(2):161-176. doi:10.1002/jrsm.57PubMedGoogle ScholarCrossref
Fayyazi  A, Khajeh  A, Ghazavi  A, Sangestani  M.  Omega 3 in childhood migraines: a double blind randomized clinical trial.  Iran J Child Neurol. 2016;10(1):9-13.PubMedGoogle Scholar
Cottrell  C, Drew  J, Gibson  J, Holroyd  K, O’Donnell  F.  Feasibility assessment of telephone-administered behavioral treatment for adolescent migraine.  Headache. 2007;47(9):1293-1302. doi:10.1111/j.1526-4610.2007.00804.xPubMedGoogle ScholarCrossref
Sartory  G, Müller  B, Metsch  J, Pothmann  R.  A comparison of psychological and pharmacological treatment of pediatric migraine.  Behav Res Ther. 1998;36(12):1155-1170. doi:10.1016/S0005-7967(98)00081-3PubMedGoogle ScholarCrossref
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(3):301-313. doi:10.1016/j.ejpain.2007.06.003PubMedGoogle ScholarCrossref
Ashrafi  MR, Salehi  S, Malamiri  RA,  et al.  Efficacy and safety of cinnarizine in the prophylaxis of migraine in children: a double-blind placebo-controlled randomized trial.  Pediatr Neurol. 2014;51(4):503-508. doi:10.1016/j.pediatrneurol.2014.05.031PubMedGoogle ScholarCrossref
Ashrafi  MR, Shabanian  R, Zamani  GR, Mahfelati  F.  Sodium valproate versus propranolol in paediatric migraine prophylaxis.  Eur J Paediatr Neurol. 2005;9(5):333-338. doi:10.1016/j.ejpn.2005.05.004PubMedGoogle ScholarCrossref
Bakhshandeh Bali  M, Rahbarimanesh  AA, Sadeghi  M, Sedighi  M, Karimzadeh  P, Ghofrani  M.  Comparison of propranolol and pregabalin for prophylaxis of childhood migraine: a randomised controlled trial.  Acta Med Iran. 2015;53(5):276-280.PubMedGoogle Scholar
Battistella  PA, Ruffilli  R, Moro  R,  et al.  A placebo-controlled crossover trial of nimodipine in pediatric migraine.  Headache. 1990;30(5):264-268. doi:10.1111/j.1526-4610.1990.hed3005264.xPubMedGoogle ScholarCrossref
Bidabadi  E, Mashouf  M.  A randomized trial of propranolol versus sodium valproate for the prophylaxis of migraine in pediatric patients.  Paediatr Drugs. 2010;12(4):269-275. doi:10.2165/11316270-000000000-00000PubMedGoogle ScholarCrossref
Bruijn  J, Duivenvoorden  H, Passchier  J, Locher  H, Dijkstra  N, Arts  WF.  Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial.  Cephalalgia. 2010;30(12):1426-1434. doi:10.1177/0333102410365106PubMedGoogle ScholarCrossref
Fallah  R, Divanizadeh  MS, Karimi  M, Mirouliaei  M, Shamszadeh  A.  Topiramate and propranolol for prophylaxis of migraine.  Indian J Pediatr. 2013;80(11):920-924. doi:10.1007/s12098-013-0976-0PubMedGoogle ScholarCrossref
Fallah  R, Fazelishoroki  F, Sekhavat  L.  A randomized clinical trial comparing the efficacy of melatonin and amitriptyline in migraine prophylaxis of children.  Iran J Child Neurol. 2018;12(1):47-54.PubMedGoogle Scholar
Gelfand  AA, Qubty  W, Patniyot  I,  et al.  Home-based trials in adolescent migraine: a randomized clinical trial.  JAMA Neurol. 2017;74(6):744-745. doi:10.1001/jamaneurol.2017.0285PubMedGoogle ScholarCrossref
Lakshmi  CV, Singhi  P, Malhi  P, Ray  M.  Topiramate in the prophylaxis of pediatric migraine: a double-blind placebo-controlled trial.  J Child Neurol. 2007;22(7):829-835. doi:10.1177/0883073807304201PubMedGoogle ScholarCrossref
Ludvigsson  J.  Propranolol used in prophylaxis of migraine in children.  Acta Neurol Scand. 1974;50(1):109-115. doi:10.1111/j.1600-0404.1974.tb01350.xPubMedGoogle ScholarCrossref
MacLennan  SC, Wade  FM, Forrest  KML, Ratanayake  PD, Fagan  E, Antony  J.  High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial.  J Child Neurol. 2008;23(11):1300-1304. doi:10.1177/0883073808318053PubMedGoogle ScholarCrossref
Santucci  M, Cortelli  P, Rossi  PG, Baruzzi  A, Sacquegna  T.  L-5-hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study.  Cephalalgia. 1986;6(3):155-157. doi:10.1046/j.1468-2982.1986.0603155.xPubMedGoogle ScholarCrossref
Slater  SK, Nelson  TD, Kabbouche  MA,  et al.  A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine.  Cephalalgia. 2011;31(8):897-905. doi:10.1177/0333102411406755PubMedGoogle ScholarCrossref
Sorge  F, Marano  E.  Flunarizine vs placebo in childhood migraine: a double-blind study.  Cephalalgia. 1985;5(2)(suppl 2):145-148.PubMedGoogle ScholarCrossref
Togha  M, Malamiri  RA, Rashidi-Ranjbar  N, Asa  S, Mahvelati  F, Ashrafi  MR.  Efficacy and safety of cinnarizine in the prophylaxis of migraine headaches in children: an open, randomized comparative trial with propranolol.  Acta Neurol Belg. 2012;112(1):51-55. doi:10.1007/s13760-012-0011-7PubMedGoogle ScholarCrossref
Tonekaboni  SH, Ghazavi  A, Fayyazi  A,  et al.  Prophylaxis of childhood migraine: topiramate versus propranolol.  Iran J Child Neurol. 2013;7(1):9-14.PubMedGoogle Scholar
Locher  C, Koechlin  H, Zion  SR,  et al.  Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: a systematic review and meta-analysis.  JAMA Psychiatry. 2017;74(10):1011-1020. doi:10.1001/jamapsychiatry.2017.2432PubMedGoogle ScholarCrossref
Parellada  M, Moreno  C, Moreno  M, Espliego  A, de Portugal  E, Arango  C.  Placebo effect in child and adolescent psychiatric trials.  Eur Neuropsychopharmacol. 2012;22(11):787-799. doi:10.1016/j.euroneuro.2011.09.007PubMedGoogle ScholarCrossref
Weimer  K, Gulewitsch  MD, Schlarb  AA, Schwille-Kiuntke  J, Klosterhalfen  S, Enck  P.  Placebo effects in children: a review.  Pediatr Res. 2013;74(1):96-102. doi:10.1038/pr.2013.66PubMedGoogle ScholarCrossref
Hróbjartsson  A, Kaptchuk  TJ, Miller  FG.  Placebo effect studies are susceptible to response bias and to other types of biases.  J Clin Epidemiol. 2011;64(11):1223-1229. doi:10.1016/j.jclinepi.2011.01.008PubMedGoogle ScholarCrossref
Sterne  JAC, Gavaghan  D, Egger  M.  Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature.  J Clin Epidemiol. 2000;53(11):1119-1129. doi:10.1016/S0895-4356(00)00242-0PubMedGoogle ScholarCrossref
Sterling  TD, Rosenbaum  WL, Weinkam  JJ.  Publication decisions revisited: the effect of the outcome of statistical tests on the decision to publish and vice versa.  Am Stat. 1995;49(1):108-112.Google Scholar
Chaimani  A, Salanti  G, Leucht  S, Geddes  JR, Cipriani  A.  Common pitfalls and mistakes in the set-up, analysis and interpretation of results in network meta-analysis: what clinicians should look for in a published article.  Evid Based Ment Health. 2017;20(3):88-94. doi:10.1136/eb-2017-102753PubMedGoogle ScholarCrossref
Faria  V, Linnman  C, Lebel  A, Borsook  D.  Harnessing the placebo effect in pediatric migraine clinic.  J Pediatr. 2014;165(4):659-665. doi:10.1016/j.jpeds.2014.06.040PubMedGoogle ScholarCrossref
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