Skip to main content
SpringerLink
Log in

Efficacy of diphenhydramine against cough in humans: a review

  • Review Paper
  • Published:
Pharmacy World & Science Aims and scope Submit manuscript

Abstract

Aim

To determine the efficacy of diphenhydramine against cough due to respiratory infection or irritation in patients/subjects without comorbidities.

Method

Two reviewers independently identified English language studies, searching on: clinical trials, randomized, diphenhydramine (OR dimenhydrinate), antitussive agents, cough (combine using AND). Sources were: Medline (1966–2005), Embase (1980–2005), Cochrane and references from retrieved articles. Two other reviewers, blinded to study origin selected studies, inclusion criteria being: diphenhydramine monotherapy against placebo, double-blinded, randomized, clinical trial, intention-to-treat, dropout information. The blinded reviewers evaluated the selected studies on a quality scale.

Results

Eleven articles were identified, 7 were rejected (4 not placebo controlled, 2 had no diphenhydramine, 1 not blinded), leaving 4 articles, that were included in the evaluation and scored 20, 21, 25 and 26 out of a maximum of 32. In these selected studies, a total of 162 people were examined, 65 on diphenhydramine, 63 on placebo and 34 in a crossover setting. There was a total of 13 dropouts. The crossover studies demonstrated significant effect; 27–56% reduction in 20 healthy volunteers and 21–26% reduction in 13 patients (originally 14, one outlier left out), whereas the active versus placebo studies did not.

Conclusion

In spite of the 60 years that the substance has been on the market, only few studies have properly evaluated the effect of diphenhydramine against cough. Presumptions about efficacy of diphenhydramine against cough in humans are not univocally substantiated in literature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anonymous. Parke Davis & Co. - Benylin Expectorant; Opportunity for Hearing on Proposal to Deny Approval of Supplemental New Drug Application. Docket No. 76–0483. Federal Register 1976;41(231):52537–9. U.S. FDA, Center for Drug Evaluation and Research. Available from: http://www.fda.gov/cder/otcmonographs/Cold&Cough/antitussive_benylin_expectorant_deny_approval_suppl_NDhttp://194.192.187.171/mdxcgi/prodindx.exe?CTL=/mdx/mdxcgi/MEGAT.SYS&SYS = 2&SET = 80A045834422809E38F00&POS = 7601795&T = 1614A_19761130.pdf Cited 19 May 2006.

  2. Garnett WR. Diphenhydramine—A monograph. Am Pharm 1986;NS26&107(2):35–40.

    Google Scholar 

  3. MARTINDALE PRODUCT INDEX {diphenhydramine}. Available from Scandinavian Medical Information. http://www.smi.dk/index_mpas.html Cited 23 March 2006.

  4. Sérlyfjaskrá (Medicinal Product Information). Icelandic Medicines Control Agency. Available from http://www.vefpostur.lyfjastofnun.is/focal/gnh52.nsf/TOC/24D67F0E6CD52B7F00256ECA003FF6A5/$FILE/Pektólín.doc Cited 19 May 2006.

  5. Smith MBH, Feldman W. Over-the-counter cold medications: a critical review of clinical trials between 1950 and 1991. JAMA 1993;269:2258–63.

    Article  PubMed  CAS  Google Scholar 

  6. Lovell S. Cough medicines. On Continuing Practice 1982;9(4):21–4.

  7. Katcher ML. Cold, cough, and allergy medications: uses and abuses. Pediatr Rev 1996;17(1):12–7.

    Article  PubMed  CAS  Google Scholar 

  8. Corrao WM. Chronic cough: an approach to management. Compr Ther 1986;12(7):14–9.

    PubMed  CAS  Google Scholar 

  9. Phelan PD. Symptomatic treatment of cough in children. Curr Ther 1986;27/4:77–82.

    Google Scholar 

  10. Irwin RS, Curley FJ, Pratter MR. The effects of drugs on cough. Eur J Respir Dis 1987;71(Suppl.153):173–81.

    Google Scholar 

  11. Micromedex. Drug consults. Antitussive agents—comparative efficacy. Diphenhydramine. Available from Scandinavian Medical Information. http://www.smi.dk/index_mpas.html Cited 23 March 2006.

  12. Banner AS. Cough: physiology, evaluation and treatment. Lung 1986;164:79–92.

    Article  PubMed  CAS  Google Scholar 

  13. Eddy NB, Friebel H, Hahn KJ, Halbach H. Codeine and its alternates for pain and cough relief. 3. The antitussive action of codeine–mechanism, methodology and evaluation. Bull World Health Organ 1969;40(3):425–454.

    PubMed  CAS  Google Scholar 

  14. Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998;52:377–384.

    Article  PubMed  CAS  Google Scholar 

  15. Matts SG. A trial of Lotussin and linctus diphenhydramine in patients with an irritant cough. J Int Med Res 1977;5(6):470–2.

    PubMed  CAS  Google Scholar 

  16. Packman EW, Ciccone PE, Wilson J, Masurat T. Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans. Int J Clin Pharmacol Ther Toxicol 1991;29:218–22.

    PubMed  CAS  Google Scholar 

  17. Lilienfield LS, Rose JC, Princiotto JV. Antitussive activity of diphenhydramine in chronic cough. Clin Pharmacol Ther 1976;19:421–5.

    PubMed  CAS  Google Scholar 

  18. Danzon A, Lacroix J, Infante-Rivard C, Chicoine L. A double-blind clinical trial on Diphenhydramine in Pertussis. Acta Paediatr Scand 1988;77(4):614–5.

    PubMed  CAS  Google Scholar 

  19. Paul IM, Yoder KE, et al. Effect of dextrometorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics 2004;114:85–90.

    Article  Google Scholar 

  20. Weippl G. Therapeutic approaches to the common cold in children. Clin Ther 1984;6:475–82.

    PubMed  CAS  Google Scholar 

  21. Middleton RSW. Double blind trial in general practice comparing the efficacy of “Benylin Day and Night” and paracetamol in the treatment of the common cold. Br J Clin Pract 1981;35:297–300.

    PubMed  CAS  Google Scholar 

  22. Jaffe GV, Grimshaw JJ. Benylin Expectorant versus Actifed Expectorant in the treatment of acute cough. Br J Clin Pract 1985;39:238–42.

    PubMed  CAS  Google Scholar 

  23. Jayaram S, Desai A. Efficacy and safety of Ascoril Expectorant and other cough formula in the treatment of cough management in paediatric and adult patients—a randomised double-blind comparative trial. J Indian Med Assoc 2000;98:68–70.

    PubMed  CAS  Google Scholar 

  24. Curley FC, Irvin RS, Pratter MR, et al. Cough and the common cold. Am Rev Respir Dis 1988;138:305–11.

    PubMed  CAS  Google Scholar 

  25. Hutton N, Wilson MH, Mellits D, et al. Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial. J Pediatr 1991;118:125–30.

    Article  PubMed  CAS  Google Scholar 

  26. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 2005;58(9):882–93.

    Article  PubMed  Google Scholar 

  27. Kleinschmidt H. [Attempt to test a new antitussive agent] [In German] Z Allgemeinmed. 1974;50(4):185–7.

  28. Elberg M. [The treatment of dry cough in orhinolaryngology] [In German] ZFA (Stuttgart). 1976;52(10):542–3.

  29. Weilacher JS [Cough and its treatment with a new cough-blocking drug] [In German]. Z Allgemeinmed. 1972;48(4):185–7.

    Google Scholar 

  30. Moher D, Jadad AR, Nichol G, et al. Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. Control Clin Trials 1995;16:62–73.

    Article  PubMed  CAS  Google Scholar 

  31. Goodman SN, Berlin J, Fletcher SW, Fletcher RH Manuscript quality before and after peer review and editing at Annals of Internal Medicine. Ann Intern Med 1994;121(1):11–21.

    PubMed  CAS  Google Scholar 

  32. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding Necessary? Control Clin Trials 1996;17:1–12.

    Article  PubMed  CAS  Google Scholar 

  33. Directive 2004/24/Ec of The European Parliament and of The Council. Official Journal of the European Union 2004(30.4) L 136/85–90. Available from the homepage of European Commission, Enterprise and Industry, Pharmaceuticals at http://www.ec.europa.eu/enterprise/pharmaceuticals/review/doc/final_publ/dir_2004_24_20040430_en.pdf Cited 22 August 2006.

Download references

Acknowledgments

The study was done partly in the authors’ own time and partly while the first author was on a post doctoral fellow grant at the University of Toronto. The authors want to thank for constructive reviewer comments and editorial comments. The authors have no conflicts of interests to declare.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Pharmacotherapy, Section for Social Pharmacy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Ingunn Björnsdóttir

  2. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada

    Thomas Ray Einarson

  3. Department of Pharmacology and Toxicology, University of Iceland, Reykjavik, Iceland

    Lárus Steinþór Guðmundsson

  4. Faculty of Pharmacy, University of Iceland, Reykjavík, Iceland

    Rannveig Alma Einarsdóttir

Authors
  1. Ingunn Björnsdóttir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Ray Einarson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lárus Steinþór Guðmundsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rannveig Alma Einarsdóttir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ingunn Björnsdóttir.

Appendices

Appendix 1

Study Inclusion Sheet to assess appropriateness of studies for meta-analysis/critical-review

Clinical trial

Yes

No

Do not know

Blinding

Not

Single

Double

English

Yes

No

Abstract English Not main text

Subjects 1 year and older

Yes

No

Do not know

Both genders

Yes

No

Do not know

Diagnosis of cough, method:

Associated disorders

Yes

No

Do not know

Patient entered on a previous date

Yes

No

Do not know

Intention-to-treat study

Yes

No

Do not know

Product with more than one active ingredient

Yes

No

Do not know

Cough treatment with more than one product

Yes

No

Do not know

Information about dropouts

Yes

No

Do not know

Randomized

Yes

No

Do not know

Comparison group

No treatment

Non-drug

Placebo

Other drug

Do not know

Outcome

Success

Failure

Other

Number of observations

 

Summaries of outcomes

 

Number of dropouts

 

Reasons for dropout

 
  1. ADE = Adverse Drug Event

Appendix 2

Less-than-perfect quality: number of missing points* on the Downs & Black scale [14].

Study

Question / (max. points)

3 (1)

5 (2)

8 (1)

11 (1)

12 (1)

13 (1)

24 (1)

25 (1)

27 (5)

Packman et al. [16]

1

1

1

1

1

1

1

 

5

Lilienfield et al. [17]

1

1

 

1

1

1

 

1

5

Danzon et al. [18]

 

2

  

1

   

4

Paul et al. [19]

 

1

  

1

   

4

  1. * A point can be missing either because of a “no” to the question or because of an “unable to determine” score.
  2. 3. Are the characteristics of the patients included in the study clearly described?
  3. 5. Are the distributions of principal confounders in each group of subjects to be compared clearly described?
  4. 8. Have all important adverse events that may be a consequence of the intervention been reported?
  5. 11. Were the subjects asked to participate in the study representative of the entire population from which they were recruited?
  6. 12. Were those subjects who were prepared to participate representative of the entire population from which they were recruited?
  7. 13. Were staff, places, and facilities where the patients were treated, representative of the treatment the majority of patients receive?
  8. 24. Was the randomization intervention assignment concealed from both patients and health care staff until recruitment was complete and irrevocable?
  9. 25. Was there adequate adjustment for confounding in the analyses from which the main findings were drawn?
  10. 27. Did the study have sufficient power to detect a clinically important effect where the probability value for a difference being due to chance is less than 5%?

Rights and permissions

Reprints and permissions

About this article

Cite this article

Björnsdóttir, I., Einarson, T.R., Guðmundsson, L.S. et al. Efficacy of diphenhydramine against cough in humans: a review. Pharm World Sci 29, 577–583 (2007). https://doi.org/10.1007/s11096-007-9122-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-007-9122-2

Keywords

Search

Navigation