Evidence-Based Practice
A Peer-Reviewed Journal of the Family Physicians Inquiries Network
EDITORIAL
3 Where’s the harm?
DIVING FOR PURLs
4 Starting solids early
Fetal fibronectin and preterm birth
PEDIATRICS
5 Prognosis after therapy
for teenage depression
HELPDESK ANSWERS
6 Antidepressants for patients with chronic
neuropathic pain
7 Best pharmacologic treatment for gastroparesis
8 Tilt testing for dehydration
9 Best treatment for vertebral
body compression fractures
10 Negative pressure wound therapy
for acute surgical wounds
Sensitivity and specificity of RAST
in allergic rhinitis
11 Treatment options for Chlamydia trachomatis
in pregnancy
12 Is it safe to breastfeed if the mother has chronic
hepatitis B?
13 Coffee for patients with tachycardia
14 What is the best pharmacologic management
of insomnia in patients with COPD?
E1 Telephone counseling and weight loss
in obese adolescents
E2 Allopurinol for preventing recurrent gout attacks
E3 EMLA cream versus placebo or dorsal penile
block for pain of circumcision in newborn boys
CT coronary angiogram for evaluation of CAD
E5 Raw food diet for the prevention or treatment
of diabetes
E6 Adequacy of self-collection for gonorrhea
and Chlamydia screening in MSMs
E7 Medications for pediatric patients
with depression
SPOTLIGHT ON PHARMACY
15 Safety of DPP-4 inhibitor plus
metformin therapy in elderly patients
V O L U M E 19 N U M B E R 9 SEPT EM BER 2016
IN DEPTH
Do over-the-counter remedies relieve cough
in acute upper respiratory infections?
Evidence-based answer
In children, over-the-counter (OTC) antitussives, antihistamines,
and mucolytics do not appear to reduce cough symptoms (SOR: A,
systematic review of RCTs). Honey modestly reduces cough frequency
in children compared with no treatment, but is not more effective than
dextromethorphan (SOR: A, systematic review of RCTs). Vapor rub is
more effective than no treatment in children for both cough severity and
frequency (SOR: B, RCT). In adults, dextromethorphan reduces cough
compared with placebo whereas guaifenesin has mixed results (SOR:
A, systematic review of RCTs). High-dose zinc acetate reduces cough
duration in adults if started within 24 hours of symptoms (SOR: A, meta-
analysis of RCTs).
Evidence summary
A 2014 systematic review of RCTs examined the effectiveness of OTC
medications for the treatment of cough in acute upper respiratory
infections (URIs) in children and adults.1 Ten trials (N=885, age range
6 months to 22 years) evaluated OTC cough remedies including
antitussives such as dextromethorphan (4 studies); antihistamines such
as diphenhydramine, clemastine, and chlorpheniramine (3 studies); the
mucolytic agent letosteine (1 study); and antihistamine-decongestant
combinations (2 studies).
No difference was noted in cough relief measured by child- or parent-
reported symptom scores or sleep duration with these medications
versus placebo, with the exception of 1 study (n=40) of the mucolytic
letosteine (not available in the United States), which showed a 2-point
symptom score decrease on a 4-point scale after 3 days of treatment
(P<.01).1
In adults, 9 single-dose trials of 30 mg dextromethorphan studied
cough outcomes for up to 3 hours. A report of 3 RCTs (n=451 adults)
found dextromethorphan decreased mean recorded cough counts by
19% to 36% over placebo (P<.05), while a meta-analysis of 5 RCTs
Evidence-Based Practice / Vol. 19, No. 9 1
In Depth
(n=710) found dextromethorphan decreased cough
bouts, cough effort, and cough latency by 12% to 17%
compared with placebo (P<.004). One small RCT (n=44)
found no benefit for dextromethorphan compared with
placebo in cough frequency or cough scores.1
In 3 trials studying the effect of guaifenesin, 1 trial
(480 mg every 6 hours for 30 hours, n=65) showed no
benefit, while another trial (extended-release 1,200 mg
twice daily for 7 days, n=378) found a mean decrease in
symptom score of 2.6 using an 8-item symptom score
(P=.04) at day 4, but no benefit at day 7 compared
with placebo. In the final trial (200 mg 4 times daily for
3 days, n=239), more patients taking guaifenesin
reported a “helpful” reduction in cough compared with
placebo (75% vs 31%; P<.01) over a 3-day period.1
A 2014 systematic review of 3 RCTs (N=568)
compared honey with diphenhydramine,
dextromethorphan, placebo, and no treatment for the
treatment of acute cough in children aged 1 to 18 years.2
All studies were for single-night durations. Cough
frequency was measured by caregivers using a 7-point
Likert scale with answers ranging from “not at all” to
“extremely.”
Honey administered 30 minutes before bedtime was
found moderately more effective in reducing frequency
of cough compared with no treatment (2 trials, n=154;
mean difference [MD] –1.1; 95% CI, –1.5 to –0.6) and
compared with placebo (1 trial, n=300; MD –1.9; 95%
CI, –3.4 to –1.3). Honey did not differ significantly
from dextromethorphan in reducing cough frequency
in 2 studies (n=149), whereas honey reduced cough
frequency better than diphenhydramine (1 trial, n=80;
MD –0.57; 95% CI –0.9 to –0.2).2
A partially blinded RCT (N=138) compared vapor
rub, petrolatum, and no treatment for nocturnal cough
with 2 consecutive days of surveys using a validated
pediatric cough questionnaire, with each item rated on
a 7-point scale ranging from “not severe at all” to “very
GLOSSARY
ARR=absolute risk reduction HR=hazard ratio
CDC=Centers for Disease Control LOE=level of evidence
and Prevention MRI=magnetic resonance imaging
CI=confidence interval NNH=number needed to harm
CT=computed tomography NNT=number needed to treat
FDA=US Food and Drug Administration NSAID=nonsteroidal anti-inflammatory drug
2 Evidence-Based Practice / September 2016
severe.”3 Participants received jars of 5 mL vapor rub
(for patients aged 2–5 years) or 10 mL vapor rub (for
patients aged 6–11 years), equal volumes of petrolatum,
or an empty jar. As a blinding strategy, parents were
instructed to place vapor rub into their own nostrils
and their child’s nostrils prior to applying study
material onto the neck and chest area and rubbing in
for 1 minute.
For both cough severity and frequency, vapor rub
was significantly better than no treatment (change
on 7-point scale of –2.0 vs –1.2 and –2.5 vs –1.1,
respectively; P<.01 for both comparisons), but not
significantly better than petrolatum. Children treated
with vapor rub and their parents were both more able
to sleep than children in the petrolatum group (change
on 7-point scale of –2.5 vs –1.6; P=.006).3
A 2015 systematic review of 3 RCTs (N=199)
examined duration of URI symptoms with use of high-
dose zinc acetate (1 lozenge every 2–3 hours while awake,
mean daily zinc dose 80–92 mg) compared with placebo
in young adults.4 The study showed a 46% reduction in
duration of days with cough (95% CI, 28%–64%) when
zinc acetate was used within 24 hours of symptom onset
for a total treatment period of less than 2 weeks. EBP
Sandy Robertson, PharmD
Mark Robinson, MD
Amanda Schultz, MD
Rachel Villella, DO
Cabarrus FMRP
Concord, NC
REFERENCES
1. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough
in children and adults in community settings. Cochrane Database Syst Rev. 2014;
(11):CD001831. [STEP 1]
2. Oduwole O, Meremikwu MM, Udoh EE. Honey for acute cough in children. Cochrane
Database Syst Rev. 2014; (12):CD007094. [STEP 1]
3. Paul IA, Beiler JS, King TS, et al. Vapor rub, petrolatum, and no treatment for children with
nocturnal cough and cold symptoms. Pediatrics. 2010; 126(6):1092–1099. [STEP 2]
4. Harri Hemilä, Elizabeth Chalker. The effectiveness of high dose zinc acetate lozenges on
various common cold symptoms: a meta-analysis. BMC Fam Pract. 2015; 16:24. [STEP 2]
OR=odds ratio
RCT=randomized controlled trial
RR=relative risk
SOR=strength of recommendation
SSRI=selective serotonin reuptake inhibitor
WHO=World Health Organization