Clinical Review & Education

JAMA Clinical Evidence Synopsis

Antiviral Agents Added to Corticosteroids

for Early Treatment of Adults With Acute Idiopathic
Facial Nerve Paralysis (Bell Palsy)
Frank Sullivan, FRSE; Fergus Daly, PhD; Ildiko Gagyor, MD

CLINICAL QUESTION Compared with oral corticosteroids alone, are oral antiviral drugs
associated with improved outcomes when combined with oral corticosteroids in patients
presenting within 72 hours of the onset of Bell palsy?

BOTTOM LINE Compared with oral corticosteroids alone, the addition of acyclovir,
valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy
was associated with a higher proportion of people who recovered at 3- to 12-month
follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result
estimates, and risk of bias.

Introduction Summary of Findings

Bell palsy affects 1 in 60 persons at some stage of their life.1 The
association of oral corticosteroids alone with corneal protection
in patients with Bell palsy is well established.2,3 This JAMA Clinical
Evidence Synopsis summarizes a Cochrane review4 that evalu-
ated the association of antiviral therapies plus oral corticosteroids
compared with oral corticosteroids alone for patients presenting
within 72 hours of onset of Bell palsy.4
Evidence Profile
No. of studies overall: 8
No. of randomized clinical trials: 8
Study years: Conducted, 1994-2011; published,
1996-2013
No. of patients: 1315
Men: 54% Women: 46%
Race/ethnicity: Not reported
Age, mean (range): 43.6 years (14-84 years)
Settings: Primary care and hospital clinics
Countries: China, Japan, Korea, Scandinavia, Scotland,
Spain, United States, and Uruguay
Comparison: Antivirals vs placebo or no treatment
among people taking oral corticosteroids.
Primary outcomes: Incomplete recovery (the equivalent
of House-Brackmann scale grade of II or worse) at
end of study (3-12 months) based on use of the
House-Brackmann scale, Sunnybrook facial grading scale,
or Yanagihara scale.5
Secondary outcomes: (1) Motor synkinesis (an anomalous
nerve regeneration leading to involuntary movements)
or crocodile tears (lacrimation, salivation) at the end
of the study; (2) adverse events (nausea, dyspepsia,
constipation, or rash); and (3) incomplete
recovery at month 6 in severe cases.
Among patients receiving oral corticosteroids for Bell palsy, the
addition of antiviral therapy was associated with a lower incom-
plete recovery rate of 11.5% (77/672) compared with 16.8% (108/
643) for those treated with placebo or no treatment (risk ratio
[RR], 0.61 [95% CI, 0.39-0.97]; P = .03). The number needed to
treat for complete recovery after 3 to 12 months was 19 patients.
Treatment with corticosteroids alone was associated with better
outcomes for 29.4% (113/384) compared with 15.1% (58/384) for
those treated with antivirals alone (RR, 2.82 [95% CI, 1.09-7.32];
P = .03).
Treatment with antivirals alone was associated with
no benefit compared with placebo (30.6% [101/330] vs 27.7%
[91/328], respectively; RR, 1.10 [95% CI, 0.87-1.40]; P = .41). For
people with severe Bell palsy (grades of V or VI on the House-
Brackmann scale or the equivalent on other scales), therapy with
antivirals plus corticosteroids was associated with a lower rate of
incomplete recovery at 6-month follow-up of 17.2% (41/238)
compared with the rate of 28.8% (69/240) for patients treated
with corticosteroids alone (RR, 0.64 [95% CI, 0.41-0.99];
P = .049).
In 2 studies involving 469 participants, antiviral therapy plus
corticosteroids was associated with a lower rate of long-term
sequelae (motor synkinesis and crocodile tears) of 11% (26/237)
compared with the rate of 19.4% (45/232) for those treated with
corticosteroids plus placebo or no treatment (RR, 0.56 [95% CI,
0.36-0.87]; P = .01). Adverse event data were available in 3 stud-
ies including 877 participants. In trials comparing antivirals plus
corticosteroids with coricosteroids plus placebo or no treatment,
the adverse event rate was 12.5% (55/440) vs 10.8% (47/437),
respectively (RR, 1.18 [95% CI, 0.83-1.69]; P = .42).
Discussion
Among 1315 patients who participated in 8 randomized clinical
trials (Figure), the addition of an antiviral agent (acyclovir, valacy-
clovir, or famcyclovir) to oral corticosteroids was associated with

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 JAMA Clinical Evidence Synopsis Clinical Review & Education

Figure. Antivirals Plus Corticosteroids vs Corticosteroids Plus Placebo or No Treatment for Patients With Bell Palsy

Antiviral Plus Corticosteroids Corticosteroids Alone

No. With No. With Favors Favors
Incomplete Total No. of Incomplete Total No. of Antivirals Plus Corticosteroids
Study Recovery Participants Recovery Participants Risk Ratio (95% CI) Corticosteroids Alone
Li, 1997 4 25 13 21 0.26 (0.10-0.67)
Adour, 1996 4 53 11 46 0.32 (0.11-0.92)
Hato, 2007 4 114 11 107 0.34 (0.11-1.04)
Yeo, 2008 3 44 7 47 0.46 (0.13-1.66)
Kawaguchi, 2007 8 84 9 66 0.70 (0.29-1.71)
Engström, 2008 42 206 50 210 0.86 (0.60-1.23)
Vázquez, 2008 3 22 2 19 1.30 (0.24-6.96)
Sullivan, 2007 9 124 5 127 1.84 (0.64-5.35)
Total 77 672 108 643 0.61 (0.39-0.97)

0.1 1.0 10
Risk Ratio (95% CI)

The size of the data markers is proportional to the study’s weight in the meta-analysis.

lower rates of incomplete recovery and long-term sequelae at 3 to
12 months compared with oral corticosteroids alone.
Limitations
The analyses are limited by data heterogeneity, imprecision of the
study results, and risk of bias. Some of the trials were small; other
trials did not meet current best standards in allocation conceal-
ment and blinding. Only 4 studies provided data on severe cases
(n = 487). There were no studies that included children.
Comparison of Findings With Current Practice Guidelines
Guidelines from the American Academy of Otolaryngology
and the Canadian Society of Otolaryngology recommend using
corticosteroids alone but suggest that clinicians consider combin-
ing corticosteroids with antiviral therapy in severe cases.6,7 Data
from this review suggest that the combination of oral corticoste-
roids plus antiviral therapies is associated with lower rates of
incomplete recovery compared with oral corticosteroids alone
(RR, 0.61; 95% CI, 0.39-0.97). However, the quality of the evi-
dence is low.
Areas in Need of Further Study
An individual patient meta-analysis that includes an analysis accord-
ing to severity of the Bell palsy and patient subgroups based on age
may be warranted to identify subgroups of patients, such as chil-
dren and patients with facial paralysis of varying severity, who may
benefit from the addition of antivirals to corticosteroids and those
who may not.8

ARTICLE INFORMATION
Author Affiliations: UTOPIAN FMTU, North York
General Hospital, Toronto, Ontario, Canada
(Sullivan); Department of Family and Community
Medicine and Dalla Lana School of Public Health,
University of Toronto, Ontario, Canada (Sullivan);
Scientist Institute for Clinical Evaluative Sciences,
Toronto, Ontario, Canada (Sullivan); Frontier
Science Ltd, Grampian View, Scotland (Daly);
Department of General Practice, Goettingen
University Medical Center, Goettingen, Germany
(Gagyor).
Corresponding Author: Frank Sullivan, FRSE,
University of Toronto, Department of Family and
Community Medicine, 500 University Ave, Toronto,
ON M5G1V7, Canada (frank.sullivan@nygh.on.ca).
Section Editor: Mary McGrae McDermott, MD,
Senior Editor.
Conflict of Interest Disclosures: The authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
Submissions: We encourage authors to submit
papers for consideration as a JAMA Clinical
Evidence Synopsis. Please contact Dr McDermott at
mdm608@northwestern.edu.
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5. Fattah AY, Gurusinghe AD, Gavilan J, et al;
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