Non‐steroidal anti‐inflammatory drugs for the common cold

Soo Young Kim; Yoon‐Jung Chang; Hye Min Cho; Ye‐Won Hwang; Yoo Sun Moon

doi:10.1002/14651858.CD006362.pub4

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Figure 1

'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies

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Figure 2

'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study

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Analysis 1.1

Comparison 1 NSAIDs versus placebo, global effect, Outcome 1 Sum of overall symptom score (random‐effects model).

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Analysis 1.2

Comparison 1 NSAIDs versus placebo, global effect, Outcome 2 Moderate to marked severity.

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Analysis 1.3

Comparison 1 NSAIDs versus placebo, global effect, Outcome 3 Duration of colds (random‐effects model).

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Analysis 1.4

Comparison 1 NSAIDs versus placebo, global effect, Outcome 4 Duration of restriction of daily activities.

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Analysis 2.1

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 1 Throat irritation score (fixed‐effect model).

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Analysis 2.2

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 2 Headache score (random‐effects model).

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Analysis 2.3

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 3 Score of pain in muscles/joints score (fixed‐effect model).

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Analysis 2.4

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 4 Malaise score (fixed‐effect model).

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Analysis 2.5

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 5 Chilliness score (random‐effects model).

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Analysis 2.6

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 6 Nose irritation score.

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Analysis 2.7

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 7 Score of pain on swallowing.

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Analysis 2.8

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 8 Eye itching score.

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Analysis 2.9

Comparison 2 NSAIDs versus placebo, analgesic effect, Outcome 9 Earache score.

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Analysis 3.1

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 1 Cough score (random‐effects model).

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Analysis 3.2

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 2 Sneezing score (fixed‐effect model).

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Analysis 3.3

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 3 Total number of sneezes.

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Analysis 3.4

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 4 Rhinorrhoea score (fixed‐effect model).

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Analysis 3.5

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 5 Nasal obstruction score (fixed‐effect model).

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Analysis 3.6

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 6 Nasal obstruction score > 5.

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Analysis 3.7

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 7 Total number of nose blows.

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Analysis 3.8

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 8 Total mucus weight.

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Analysis 3.9

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 9 Total tissue number count.

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Analysis 3.10

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 10 Score of dryness in the nose.

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Analysis 3.11

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 11 Score of reduced sense of smell.

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Analysis 3.12

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 12 Hoarseness score.

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Analysis 3.13

Comparison 3 NSAIDs versus placebo, non‐analgesic effect, Outcome 13 Fatigue score.

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Analysis 4.1

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 1 Overall side effects (random‐effects model).

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Analysis 4.2

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 2 GI complaint (fixed‐effect model).

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Analysis 4.3

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 3 Lethargy/drowsiness (fixed‐effect model).

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Analysis 4.4

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 4 Feeling hyperactive.

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Analysis 4.5

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 5 Feeling more awake.

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Analysis 4.6

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 6 Flushed face.

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Analysis 4.7

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 7 Difficulty sleeping.

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Analysis 4.8

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 8 Light‐headedness.

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Analysis 4.9

Comparison 4 NSAIDs versus placebo, adverse effects, Outcome 9 Dry mouth.

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Analysis 5.1

Comparison 5 Head to head comparison, global effect, Outcome 1 Global improvement rating, marked improvement (fixed‐effect model).

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Analysis 5.2

Comparison 5 Head to head comparison, global effect, Outcome 2 Global improvement rating, moderate to marked improvement (fixed‐effect model).

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Summary of findings for the main comparison. Non‐steroidal anti‐inflammatory drugs for the common cold

Non‐steroidal anti‐inflammatory drugs for the common cold
Patient or population: patients with common cold Settings: community or care facilities or hospital Intervention: non‐steroidal anti‐inflammatory drugs
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Non‐steroidal anti‐inflammatory drugs
Sum of overall symptom score	—	The mean sum of overall symptom score in the intervention groups was 0.4 standard deviations lower (1.03 lower to 0.24 higher)	—	293 (3 studies)	⊕⊕⊕⊝ moderate¹	—
Duration of colds	—	The mean duration of colds in the intervention groups was 0.23 lower (0 to 0 higher)	—	214 (2 studies)	⊕⊕⊕⊝ moderate²	—
Throat irritation score	—	The mean throat irritation score in the intervention groups was 0.01 standard deviations lower (0.33 lower to 0.3 higher)	—	159 (2 studies)	⊕⊕⊕⊝ moderate²	—
Headache score	—	The mean headache score in the intervention groups was 0.65 standard deviations lower (1.11 to 0.19 lower)	—	159 (2 studies)	⊕⊕⊕⊝ moderate²	—
Score of pain in muscles/joints score	—	The mean pain in muscles/joints score in the intervention groups was 0.40 standard deviations lower (0.77 to 0.03 lower)	—	0 (2 studies)	See comment	—
Cough score	—	The mean cough score in the intervention groups was 0.05 standard deviations lower (0.66 lower to 0.56 higher)	—	159 (2 studies)	⊕⊕⊕⊝ moderate²	—
Rhinorrhoea score	—	The mean rhinorrhoea score in the intervention groups was 0.03 standard deviations higher (0.25 lower to 0.3 higher)	—	199 (3 studies)	⊕⊕⊕⊝ moderate²	—
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹# NSAIDs group 141, placebo group 152. ²Too small sample size.

Summary of findings for the main comparison. Non‐steroidal anti‐inflammatory drugs for the common cold

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Comparison 1. NSAIDs versus placebo, global effect

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sum of overall symptom score (random‐effects model) Show forest plot	3	293	Std. Mean Difference (IV, Random, 95% CI)	‐0.40 [‐1.03, 0.24]

2 Moderate to marked severity Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.18, 2.11]

3 Duration of colds (random‐effects model) Show forest plot	2	214	Mean Difference (IV, Random, 95% CI)	‐0.23 [‐1.75, 1.29]

4 Duration of restriction of daily activities Show forest plot	1	174	Mean Difference (IV, Fixed, 95% CI)	‐0.56 [‐1.24, 0.12]

Comparison 1. NSAIDs versus placebo, global effect

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Comparison 2. NSAIDs versus placebo, analgesic effect

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Throat irritation score (fixed‐effect model) Show forest plot	2	159	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐0.33, 0.30]

2 Headache score (random‐effects model) Show forest plot	2	159	Std. Mean Difference (IV, Random, 95% CI)	‐0.65 [‐1.11, ‐0.19]

3 Score of pain in muscles/joints score (fixed‐effect model) Show forest plot	2	114	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.40 [‐0.77, ‐0.03]

4 Malaise score (fixed‐effect model) Show forest plot	2	159	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.29 [‐0.60, 0.03]

5 Chilliness score (random‐effects model) Show forest plot	2	159	Std. Mean Difference (IV, Random, 95% CI)	‐0.03 [‐1.12, 1.06]

6 Nose irritation score Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.48, 0.40]

7 Score of pain on swallowing Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.07 [‐0.51, 0.37]

8 Eye itching score Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.14 [‐0.58, 0.30]

9 Earache score Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.59 [‐1.04, ‐0.14]

Comparison 2. NSAIDs versus placebo, analgesic effect

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Comparison 3. NSAIDs versus placebo, non‐analgesic effect

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cough score (random‐effects model) Show forest plot	2	159	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.66, 0.56]

2 Sneezing score (fixed‐effect model) Show forest plot	2	159	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.44 [‐0.75, ‐0.12]

3 Total number of sneezes Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.51 [‐0.95, ‐0.06]

4 Rhinorrhoea score (fixed‐effect model) Show forest plot	3	199	Std. Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.25, 0.30]

5 Nasal obstruction score (fixed‐effect model) Show forest plot	3	199	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.15 [‐0.43, 0.13]

6 Nasal obstruction score > 5 Show forest plot	1	27	Risk Ratio (M‐H, Fixed, 95% CI)	5.36 [0.28, 102.12]

7 Total number of nose blows Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.27, 0.61]

8 Total mucus weight Show forest plot	1	40	Std. Mean Difference (IV, Fixed, 95% CI)	0.13 [‐0.49, 0.76]

9 Total tissue number count Show forest plot	1	40	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.83, 0.42]

10 Score of dryness in the nose Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.40, 0.48]

11 Score of reduced sense of smell Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	0.08 [‐0.36, 0.51]

12 Hoarseness score Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	0.32 [‐0.12, 0.76]

13 Fatigue score Show forest plot	1	80	Std. Mean Difference (IV, Fixed, 95% CI)	0.18 [‐0.26, 0.62]

Comparison 3. NSAIDs versus placebo, non‐analgesic effect

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Comparison 4. NSAIDs versus placebo, adverse effects

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall side effects (random‐effects model) Show forest plot	2	220	Risk Ratio (M‐H, Random, 95% CI)	2.94 [0.51, 17.03]

2 GI complaint (fixed‐effect model) Show forest plot	3	189	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.17, 3.32]

3 Lethargy/drowsiness (fixed‐effect model) Show forest plot	2	110	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.14, 6.91]

4 Feeling hyperactive Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 70.02]

5 Feeling more awake Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 70.02]

6 Flushed face Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 70.02]

7 Difficulty sleeping Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 7.78]

8 Light‐headedness Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.15, 6.51]

9 Dry mouth Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 70.02]

Comparison 4. NSAIDs versus placebo, adverse effects

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Comparison 5. Head to head comparison, global effect

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global improvement rating, marked improvement (fixed‐effect model) Show forest plot	2	365	Risk Ratio (M‐H, Fixed, 95% CI)	1.52 [0.99, 2.34]

2 Global improvement rating, moderate to marked improvement (fixed‐effect model) Show forest plot	2	365	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [1.02, 1.41]

Comparison 5. Head to head comparison, global effect

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