Is there a clinical benefit with the use of codeine as a cough suppressant in COVID-19 patients compared to other available cough suppressants?

Comment by InpharmD Researcher

There is limited clinical data comparing various cough suppressants, including codeine, in patients with COVID-19. An observational survey found no difference in the perceived efficacy of codeine compared to other cough suppressants in patients with COVID-19. The U.K. National Institute for Health and Care Excellence (NICE) recommends codeine for acute symptom management of COVID-19 based on the theory that opiates can suppress the cough reflex network in the brainstem. However, associated risks with opioid use including dependence, abuse, and central nervous system adverse events may be of concern.

Background

A 2021 review article reviewed the current knowledge regarding COVID-19 cough. At the time of the article, evidence was lacking for management of COVID-19 associated cough, including codeine's place in therapy. The U.K. National Institute for Health and Care Excellence (NICE) guidelines for acute symptom management of COVID-19 recommended codeine along with other opioid-derived antitussives based on the theory that opiates can suppress the cough reflex network in the brainstem. However, associated risks with opioid use regarding dependence, abuse, and central nervous system adverse events are highlighted concerns. [1]

References:

[1] Song WJ, Hui CKM, Hull JH, et al. Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med. 2021;9(5):533-544. doi:10.1016/S2213-2600(21)00125-9
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there a clinical benefit with the use of codeine as a cough suppressant in COVID-19 patients compared to other available cough suppressants?

Level of evidence

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Please see Table 1 for your response.

 

A Survey Of Provider-Reported Use And Perceived Effectiveness Of Medications For Symptom Management In Telemedicine And Outpatient Visits For Mild COVID-19 

Design

Observational survey study 

N= 62

Objective

To assess provider-reported use of medications and their perceived effectiveness and the degree of difficulty managing specific COVID-19 symptoms 

Study Groups

Episodic care (n= 30)

Longitudinal care (n= 32)

Inclusion Criteria

Patients with mild COVID-19 with symptoms requiring acute and follow-up care

Exclusion Criteria

N/A

Methods

An online survey was sent to COVID-19 care sites at an academic medical center asking about the medications and their perceived effectiveness in treating symptoms of COVID-19 and the perceived challenge of symptoms management. Comparisons were grouped as either episodic or longitudinal sites of care. 

Duration

May 24, 2020, to June 4, 2020

Outcome Measures

 Characterized the perceived efficacy of therapeutic agents in symptom management and perceptions of difficulty in the outpatient management of symptoms associated with COVID-19

Baseline Characteristics

 

  

 

All respondents

(N= 62)

Episodic care

(n= 30)

Longitudinal care

(n= 32)

 p-value

Therapy used for cough

Honey

Dextromethorphan

Guaifenesin

Benzonatate

Codeine, hydrocodone

OTC lozenge

 

33 (53.2%)

46 (74.2%)

47 (75.8%)

52 (83.9%)

31 (50.0%)

39 (62.9%)

 

12 (40.0%)

21 (70.0%)

18 (60.0%)

22 (73.3%)

15 (50.0%)

15 (50.0%)

 

21 (65.6%)

25 (78.1%)

29 (90.6%)

30 (93.8%)

16 (50.0%)

24 (75.0%)

 

0.07

0.57

0.007

0.04

1.00

0.07

Results

Endpoint

All respondents

Episodic care

Longitudinal care

p-value

Therapies perceived as moderately or very effective

Honey (n= 33)

Dextromethorphan (n= 46)

Guaifenesin (n= 47)

Benzonatate (n= 52)

Codeine, hydrocodone (n= 31)

OTC lozenge (n= 39)

 

17 (51.5%)

31 (67.4%)

30 (63.8%)

37 (71.2%)

24 (77.4%)

20 (51.3%)

 

6 (50.0%)

12 (57.1%)

7 (38.9%)

13 (59.1%)

10 (66.7%)

7 (46.7%)

 

11 (52.4%)

19 (76.0%)

23 (79.3%)

24 (80.0%)

14 (87.5%)

13 (54.2%)

 

1.00

0.22

0.01

0.13

0.22

0.75

Symptoms perceived as very challenging

Cough (n= 54)

 

21 (38.9%)

 

12 (50.0%)

 

9 (30.0%)

 

0.17

Adverse Events

N/A

Study Author Conclusions

The increased perceived difficulty of management of lower respiratory symptoms reported by all providers may explain the high reported usage of medications for lower respiratory symptoms such as cough and shortness of breath, particularly by follow-up providers. Despite reporting high efficacy of these medications (albuterol, opioid-containing cough medication, and benzonatate), respondents still reported high difficulty, highlighting the overall challenge of managing lower respiratory infections at home. 

InpharmD Researcher Critique

The study had a low response rate, and the results were self-reported, leading to an increased risk of bias. Additionally, the study included a small sample size of 64 subjects, potentially limiting the external validity to other healthcare settings. 



References:

O'Keefe JB, Newsom LC, Taylor TH Jr. A Survey of Provider-Reported Use and Perceived Effectiveness of Medications for Symptom Management in Telemedicine and Outpatient Visits for Mild COVID-19. Infect Dis Ther. 2021;10(2):839-851. doi:10.1007/s40121-021-00432-8