Placebo Effect in the Treatment of Acute Cough in Infants and Toddlers: A Randomized Clinical Trial | Complementary and Alternative Medicine | JAMA Pediatrics | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Berger  H, Jarosch  E, Madreiter  H.  Effect of Vaporub and petrolatum on frequency and amplitude of breathing in children with acute bronchitis.  J Int Med Res. 1978;6(6):483-486.PubMedGoogle Scholar
De Blasio  F, Dicpinigaitis  PV, Rubin  BK, De Danieli  G, Lanata  L, Zanasi  A.  An observational study on cough in children: epidemiology, impact on quality of sleep and treatment outcome.  Cough. 2012;8(1):1. doi:10.1186/1745-9974-8-1.PubMedGoogle ScholarCrossref
Smith  SM, Schroeder  K, Fahey  T.  Over-the-counter (OTC) medications for acute cough in children and adults in ambulatory settings.  Cochrane Database Syst Rev. 2012;8(8):CD001831. doi:10.1002/14651858.CD001831.pub4.PubMedGoogle Scholar
Paul  IM.  Therapeutic options for acute cough due to upper respiratory infections in children.  Lung. 2012;190(1):41-44.PubMedGoogle ScholarCrossref
Jaffe  GV, Grimshaw  JJ.  Benylin expectorant versus actifed expectorant in the treatment of acute cough.  Br J Clin Pract. 1985;39(6):238-242.PubMedGoogle Scholar
Pfeiffer  WF.  A multicultural approach to the patient who has a common cold.  Pediatr Rev. 2005;26(5):170-175.PubMedGoogle ScholarCrossref
Paul  IM, Beiler  J, McMonagle  A, Shaffer  ML, Duda  L, Berlin  CM  Jr.  Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents.  Arch Pediatr Adolesc Med. 2007;161(12):1140-1146.PubMedGoogle ScholarCrossref
Shadkam  MN, Mozaffari-Khosravi  H, Mozayan  MR.  A comparison of the effect of honey, dextromethorphan, and diphenhydramine on nightly cough and sleep quality in children and their parents.  J Altern Complement Med. 2010;16(7):787-793.PubMedGoogle ScholarCrossref
Cohen  HA, Rozen  J, Kristal  H,  et al.  Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study.  Pediatrics. 2012;130(3):465-471.PubMedGoogle ScholarCrossref
Cox  N, Hinkle  R.  Infant botulism.  Am Fam Physician. 2002;65(7):1388-1392.PubMedGoogle Scholar
Hartnick  CJ, Zurakowski  D, Haver  K.  Validation of a pediatric cough questionnaire.  Ear Nose Throat J. 2009;88(11):1213-1217.PubMedGoogle Scholar
Monterrosas-Brisson  N, Ocampo  ML, Jiménez-Ferrer  E,  et al.  Anti-inflammatory activity of different agave plants and the compound cantalasaponin-1.  Molecules. 2013;18(7):8136-8146.PubMedGoogle ScholarCrossref
Phillips  KM, Carlsen  MH, Blomhoff  R.  Total antioxidant content of alternatives to refined sugar.  J Am Diet Assoc. 2009;109(1):64-71.PubMedGoogle 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.PubMedGoogle ScholarCrossref
Hutton  N, Wilson  MH, Mellits  ED,  et al.  Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.  J Pediatr. 1991;118(1):125-130.PubMedGoogle ScholarCrossref
Korppi  M, Laurikainen  K, Pietikäinen  M, Silvasti  M.  Antitussives in the treatment of acute transient cough in children.  Acta Paediatr Scand. 1991;80(10):969-971.PubMedGoogle ScholarCrossref
Taylor  JA, Novack  AH, Almquist  JR, Rogers  JE.  Efficacy of cough suppressants in children.  J Pediatr. 1993;122(5, pt 1):799-802.PubMedGoogle ScholarCrossref
Clemens  CJ, Taylor  JA, Almquist  JR, Quinn  HC, Mehta  A, Naylor  GS.  Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children?  J Pediatr. 1997;130(3):463-466.PubMedGoogle ScholarCrossref
Paul  IM, Yoder  KE, Crowell  KR,  et al.  Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents.  Pediatrics. 2004;114(1):e85-e90. doi:10.1542/peds.114.1.e85.PubMedGoogle ScholarCrossref
Martinez Gallardo  F, López Fiesco  A, Zamora  G.  Symptomatic treatment of common cold in children with a new combination of naproxen sodium plus pseudoephedrine hydrochloride: a comparative trial against pseudoephedrine syrup.  Proc West Pharmacol Soc. 1994;37:157-158.PubMedGoogle Scholar
Sakchainanont  B, Ruangkanchanasetr  S, Chantarojanasiri  T, Tapasart  C, Suwanjutha  S.  Effectiveness of antihistamines in common cold.  J Med Assoc Thai. 1990;73(2):96-101.PubMedGoogle Scholar
Unuvar  E, Yildiz  I, Kilic  A,  et al.  Is acetaminophen as effective as an antihistamine-decongestant-acetaminophen combination in relieving symptoms of acute nasopharyngitis in children? a randomised, controlled trial.  Int J Pediatr Otorhinolaryngol. 2007;71(8):1277-1285.PubMedGoogle ScholarCrossref
Eccles  R.  The powerful placebo in cough studies?  Pulm Pharmacol Ther. 2002;15(3):303-308.PubMedGoogle ScholarCrossref
Vicks Care Center. VapoRub topical ointment. Accessed September 9, 2014.
Original Investigation
Journal Club
December 2014

Placebo Effect in the Treatment of Acute Cough in Infants and Toddlers: A Randomized Clinical Trial

Journal Club PowerPoint Slide Download
Author Affiliations
  • 1Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania
  • 2Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania
JAMA Pediatr. 2014;168(12):1107-1113. doi:10.1001/jamapediatrics.2014.1609

Importance  Cough is one of the most common reasons why children visit a health care professional.

Objectives  To compare the effect of a novel formulation of pasteurized agave nectar vs placebo and no treatment on nocturnal cough and the sleep difficulty associated with nonspecific acute cough in infants and toddlers.

Design, Setting, and Participants  In this randomized clinical trial performed in 2 university-affiliated outpatient, general pediatric practices from January 28, 2013, through February 28, 2014, children 2 to 47 months old with nonspecific acute cough duration of 7 days or less were studied. Surveys were administered to parents on 2 consecutive days, the day of presentation (when no medication had been given the prior evening) and the next day (when agave nectar, placebo, or no treatment had been administered to their child before bedtime) according to a partially double-blind randomization scheme.

Interventions  A single dose of agave nectar, placebo, or no treatment administered 30 minutes before bedtime.

Main Outcomes and Measures  Cough frequency, cough severity, cough bothersomeness, congestion severity, rhinorrhea severity, and cough effect on child and parent sleep.

Results  Significant differences in symptom improvement were detected between the study groups (P < .05 for all, except P = .06 for cough bothersomeness), with agave nectar and placebo proving to be superior to no treatment, but no significant differences for any outcome were found when comparing agave nectar against placebo.

Conclusions and Relevance  In a comparison of agave nectar, placebo, and no treatment, a placebo effect was demonstrated, with no additional benefit offered by agave nectar. Health care professionals should consider the potential benefits and costs when recommending a treatment with only a placebo effect for infants and toddlers with nonspecific acute cough.

Trial Registration Identifier: NCT01721395