Dextromethorphan Use in Children

Cough is one of the main reasons why parents bring their children to the emergency department.  Approximately 3% of ED visits are due to children having a cough that is driving their parents nuts. Parents are exhausted from staying up at night with the coughing child, and they are looking for a magic elixir to cure the common cough.  Once you rule out more dire or treatable diagnoses (ex, pneumomediastinum, aspirated foreign body, croup, pertussis, or bacterial tracheitis), you can focus on helping their child feel better.  There is some evidence for honey for coughs, but not good evidence for homeopathic medications. But what about good ole OTC antitussives that contain cough suppressants such as dextromethorphan?  Do those medications work?  Let’s explore a little more to see if this is a “cure” for the common cough:

Dextromethorphan- Basics 

  • What is dextromethorphan or D-methorphan?  
    • It’s a non-opioid derivative of morphine.  
    • A synthetic analog of levorphanol, which is similar to codeine.  
    • It’s not technically an opioid, BUT the molecule is very similar to an opioid. 
    • It has no analgesic effect.  
    • It does not have addictive properties, BUT because of the side effects it is known as a drug of abuse.
    • It crosses the blood-brain barrier as a sigma opioid receptor agonist in the medulla oblongata “cough center” of the CNS to suppress the natural cough reflex.
    • See – Dextromethorphan
  • It’s the most commonly used OTC cough medication (Paul 2017) and is commonly combined with:
    • Brompheniramine – H1 receptor antagonist (antihistamine) [Pubchem- Brompheniramine] 
    • Pseudoephedrine – sympathomimetic [Pubchem- Pseudoephedrine]
    • Guaifenesin – expectorant [Pubchem-Guaifenesin]
  • There are over 125 medications that include dextromethorphan. [Schwarz 2005]  Some formulations that include: Children’s Robitussin Cough Long-Acting, Delsym, Vicks DayQuil Cough, Vicks Formula 44 Custom Care Dry Cough, Zicam Cough MAX 

Dextromethorphan- Is it helpful?

  • Many studies have been done …
  • Comparing dextromethorphan and other cough medications to placebo, or to honey, and
  • NONE of these studies show a statistically significant improvement in symptoms of cough overnight.  [Paul 2004, Paul 2007, Paul 2012, Mahmood 2010, Bhattacharya 2013]  
  • Interestingly, the coughs tended to be better on a subsequent night, no matter what the treatment, but the sleep quality of parents was poor in all groups!
  • Honey has been shown to be more effective than dextromethorphine, placebo, and other alternative cough preparations. [Mahmood 2010, Paul 2007, Paul 2012]

Dextromethorphan- Is it recommended?

  • The American Academy of Pediatrics (AAP) does NOT recommend over the counter cough medications for young children [AAP 2022]
  • The FDA does not recommend OTC cough medications for children under 2 [Tips from the FDA 2022]

Dextromethorphan- Is it harmful?

  • One study evaluated the safety of a single dose of dextromethorphan in various age groups of children and found that a single dose of medication was safe.  [Guenin 2014]  
    • But when do parents only give a single dose of a medication when cough can last for weeks?
  • A retrospective review of case series from multiple sources including the National Poison Data System and the FDA’s Adverse Event reporting system found 1716 cases of at least one adverse event between 2008 and 2014 associated with dextromethorphan. [Paul 2017]
    • 3% were related to therapeutic dosing and 60% included children younger than 4yo.
  • There are increasing reports of intentional overdose and abuse by teenagers due to euphoric and dissociative effects of this easty to obtain over the counter medication. [Romanelli 2009, Carr 2006]

Dextromethorphan- Side effects

  • Pubchem lists some of the following sides effects indicating toxicity: [Pubchem- Dextromethorphan]
    • nausea, 
    • vomiting, 
    • stupor, 
    • coma, 
    • respiratory depression, 
    • seizures, 
    • tachycardia, 
    • hyperexcitability, 
    • toxic psychosis, 
    • ataxia, 
    • nystagmus, 
    • dystonia, 
    • blurred vision, 
    • changes in muscle reflexes,
  • Since dextromethorphan works in the CNS, the side effects typically mimic side effects seen with other CNS-acting medications.
  • One case series discussed a 2 year old with ataxia, wide-based gait, and nystagus that resolved after several hours, and an infant who had episodes of stiffening and turning blue that improved after Narcan administration. [Pender 1991]
  • A case report of a 2 year old who had 3 doses of dextromethorphan/pseudoephedrine reported ataxia, psychosis, and hyperirritability. [Roberge 1999]
  • Deaths from dextromethorphan overdose are rare, but are thought to be related to respiratory suppression in overdose. [Pender 1991]

Dextromethorphan- Other interesting tidbits

  • Patients with Phenylketonuria (PKU) should be cautioned when taking this medication. Many preparations are sugar free but contain aspartame, which is metabolized to phenylalanine in the GI tract. [Pubchem- Dextromethorphan]
  • Overdoses of dextromethorphan can result as a false positive for phencyclidine in a urine drug screen. [Schwarz 2005]

Moral of the Morsel

  • It may be common… but that doesn’t make it good or useful. Many OTC medications that include dextromethorphan; evidence shows that they don’t work well.
  • Bees are the best!! Honey does have evidence to show it works, and it’s natural, so recommend honey, Honey!
  • No magical elixir… but TLC does cure all. Parents are going to be frustrated that there isn’t anything magical to make their child’s cough go away.  But if you help them realize that it won’t benefit them to give a medication that penetrates into the brain and is similar to opioids, perhaps they’ll reconsider giving OTC cough meds with dextromethorphan!

References:

  1. Ian M. Paul, Kate M. Reynolds, Ralph E. Kauffman, William Banner, G. Randall Bond, Robert B. Palmer, Randy I. Burnham & Jody L. Green (2017) Adverse events associated with pediatric exposures to dextromethorphan, Clinical Toxicology, 55:1, 25-32, DOI: 10.1080/15563650.2016.1240803
  2. PENDER, EMILY S. MD; PARKS, BRUCE R. PhD Toxicity with dextromethorphan-containing preparations: A literature review and report of two additional cases, Pediatric Emergency Care: June 1991 – Volume 7 – Issue 3 – p 163-165
  3. Guenin, E., Armogida, M. & Riff, D. Pharmacokinetic Profile of Dextromethorphan Hydrobromide in a Syrup Formulation in Children and Adolescents. Clin Drug Investig 34, 609–616 (2014). https://doi.org/10.1007/s40261-014-0210-5
  4. Raymond J Roberge, Kamal H Hirani, Paul L Rowland, Ross Berkeley, Edward P Krenzelok. Dextromethorphan- and pseudoephedrine-induced agitated psychosis and ataxia: case report. The Journal of Emergency Medicine. Volume 17, Issue 2, 1999, Pages 285-288, ISSN 0736-4679,https://doi.org/10.1016/S0736-4679(98)00193-0.
  5. National Center for Biotechnology Information. PubChem Compound Summary for CID 5360696, Dextromethorphan. https://pubchem.ncbi.nlm.nih.gov/compound/Dextromethorphan. Accessed July 28, 2022.
  6. National Center for Biotechnology Information. PubChem Compound Summary for CID 6834, Brompheniramine. https://pubchem.ncbi.nlm.nih.gov/compound/brompheniramine. Accessed July 28, 2022.
  7. National Center for Biotechnology Information. PubChem Compound Summary for CID 7028, Pseudoephedrine. https://pubchem.ncbi.nlm.nih.gov/compound/pseudoephedrine. Accessed July 28, 2022.
  8. National Center for Biotechnology Information. PubChem Compound Summary for CID 3516, Guaifenesin. https://pubchem.ncbi.nlm.nih.gov/compound/guaifenesin. Accessed July 28, 2022.
  9. Schwartz RH. Adolescent Abuse of Dextromethorphan. Clinical Pediatrics. 2005;44(7):565-568. doi:10.1177/000992280504400702
  10.   Ian M. Paul, Katharine E. Yoder, Kathryn R. Crowell, Michele L. Shaffer, Heidi S. McMillan, Lisa C. Carlson, Deborah A. Dilworth, Cheston M. Berlin; Effect of Dextromethorphan, Diphenhydramine, and Placebo on Nocturnal Cough and Sleep Quality for Coughing Children and Their Parents. Pediatrics July 2004; 114 (1): e85–e90. 10.1542/peds.114.1.e85
  11. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM. 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. doi:10.1001/archpedi.161.12.1140
  12. Frank Romanelli, Kelly M. Smith. Dextromethorphan abuse: Clinical effects and management. Journal of the American Pharmacists Association. Volume 49, Issue 2. 2009. Pages e20-e27. ISSN 1544-3191. https://doi.org/10.1331/JAPhA.2009.08091.
  13. Mahmood Noori Shadkam, Hassan Mozaffari-Khosravi, and Mohammad Reza Mozayan.A Comparison of the Effect of Honey, Dextromethorphan, and Diphenhydramine on Nightly Cough and Sleep Quality in Children and Their Parents.The Journal of Alternative and Complementary Medicine.Jul 2010.787-793.http://doi.org/10.1089/acm.2009.0311
  14. Bhattacharya, M., Joshi, N. & Yadav, S. To Compare the Effect of Dextromethorphan, Promethazine and Placebo on Nocturnal Cough in Children Aged 1–12 y with Upper Respiratory Infections: A Randomized Controlled Trial. Indian J Pediatr 80, 891–895 (2013). https://doi.org/10.1007/s12098-013-1002-2
  15. Paul, I.M. Therapeutic Options for Acute Cough Due to Upper Respiratory Infections in Children. Lung 190, 41–44 (2012). https://doi.org/10.1007/s00408-011-9319-y
  16. Carr, Brandon C. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population, Current Opinion in Pediatrics: April 2006 – Volume 18 – Issue 2 – p 184-188. doi: 10.1097/01.mop.0000193274.54742.a1
  17. AAP – Cough and cold meds in kids under four | Choosing Wisely. Choosing Wisely | Promoting conversations between providers and patients. https://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/. Published 2022. Accessed July 29, 2022.
  18. Tips from the FDA to safely treat your child’s cough and cold. U.S. Food and Drug Administration. https://www.fda.gov/consumers/consumer-updates/should-you-give-kids-medicine-coughs-and-colds#:~:text=The%20FDA%20doesn’t%20recommend,under%204%20years%20of%20age.%E2%80%9D. Published 2022. Accessed July 29, 2022.
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Christyn Magill
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