September 15, 2009 — Results from a systematic review suggest that adding an antiviral

to corticosteroid therapy for Bell's palsy might increase efficacy. Antivirals as single
agents have proven unsuccessful in activating the cranial nerve but are often used in
combination with steroids. But the practice is mired in uncertainty and has prompted
questions that investigators worked to answer in a meta-analysis published September 2
in the Journal of the American Medical Association.

"The most important point is that we found the use of steroids early in Bell's palsy is
effective," study author Gordon Guyatt, MD, from McMaster University in Hamilton,
Ontario, said during an interview.

In contrast to the primary trials, the new meta-analysis suggests that antivirals might be
beneficial when combined with steroids. "Everyone had concluded that there is no place
for antivirals, but our work suggests the possibility of an even bigger effect," Dr. Guyatt
told Medscape Neurology."Our study emphasizes the importance of comprehensive
statistical reviews."

Although the results point to a possible incremental benefit, the investigators

acknowledge that the relative risk of 0.75 did not reach statistical significance (P = .05).
It is a problem that leaves much to clinical decision-making between doctors and patients
until more studies are done.

Failed to Reach Statistical Significance

The results conflict with a small meta-analysis published in June (Arch Otolaryngol
Head Neck Surg. 2009;135:558-564). In that study, investigators looked at just 4 studies
and concluded that no treatment is established in Bell's palsy.

But after reviewing 18 randomized controlled trials of more than 2700 patients, Dr.
Guyatt and his team, led by John de Almeida, MD, from Sunnybrook Hospital in
Toronto, Ontario, disagree with that study. They report that corticosteroids were
associated with a reduced risk for unsatisfactory recovery (relative risk, 0.69; 95%
confidence interval, 0.55 to 0.87; P = .001). They found the number needed to treat to
benefit 1 person is 11.

"This evidence is not likely to be contradicted by additional clinical trials," John Steiner,
MD, from Kaiser Permanente Colorado in Denver, said in an accompanying editorial. "It
has important implications for clinical practice."

"Corticosteroids are well established," Dr. Guyatt said.

Corticosteroids Standard, Antivirals Debatable

In their June article, Drs. John Goudakos and Konstantinos Markou, from AHEPA
University Hospital and Aristotle University of Thessaloniki in Greece, said that
"treatment decisions regarding patients with Bell's palsy are doubtful and remain a
common problem in medical practice."

Many questions remain when it comes to whether to experiment with combination

therapy. "Given the possibility of marginal benefit and the absence of major harm with
antiviral therapy, clinicians may convert uncertain knowledge into definitive action by
adding an antiviral medication to a corticosteroid for their next patient with Bell's palsy,"
Dr. Steiner noted.

"Until the next generation of clinical trials is completed, clinicians and patients will have
to deal with substantial uncertainty in deciding whether to add antiviral drugs to
corticosteroids." But, he adds, the availability of generic low-cost antivirals, such as
acyclovir, and the apparent absence of major adverse effects suggest that large clinical
trials are warranted.

The authors agree that more trials are needed, but they disagree with Dr. Steiner on the
issue of cost. At roughly $20 a day for acyclovir (4000 mg) and valacyclovir (3000 mg),
the price is "not insignificant," they note — especially for an uncertain benefit.

Coauthor Ian Witterick, MD, from Mount Sinai Hospital in Toronto, Ontario, reports
receiving funding from Schering, Abbott Laboratories, and Alcon Canada.

JAMA. 2009;302:985-993. Abstract

Additional Resource

More information on Bell's Palsy is available on the National Institute of Neurological

Disorders and Stroke Web site.

Clinical Context

Bell's palsy is a common inflammatory condition of the facial nerve which can be
distressing to the patient. Both the herpes simplex virus and the varicella zoster virus
have been implicated in promoting this inflammation, and the annual incidence of Bell's
palsy is 20 to 30 cases per 100,000 persons. A total of 71% of patients with Bell's palsy
recover completely, although more severe facial paralysis is associated with a worse
prognosis.

Both corticosteroids and antiviral medications are currently used to hasten recovery from
Bell's palsy and reduce long-term rates of residual symptoms, but the research into these
treatment methods has been mixed. The current systematic review and meta-analysis
examines the efficacy of antiviral medications and corticosteroids, individually and in
combination, on outcomes of Bell's palsy.

Study Highlights
 • Researchers examined medical databases for randomized controlled trials of
treatment with corticosteroids or antiviral medications for Bell's palsy. The
literature search included studies published before March 1, 2009. All research
reported outcomes of facial recovery, synkinesis, autonomic dysfunction, and/or
adverse events.
• The primary outcome of the meta-analysis was unsatisfactory facial recovery at 4
months or longer. Researchers also examined short-term recovery at 6 weeks to
less than 4 months, autonomic dysfunction, and rates of adverse events.
• 854 studies were identified on the original search, and 18 met inclusion criteria. A
total of 8 studies evaluated corticosteroids, 7 evaluated antiviral agents, and 3
studies evaluated both agents.
• The 18 trials included a total of 2786 patients. The median follow-up time was 6
months, 1 trial included only pediatric patients, and 6 trials included pediatric
patients.
• 10 studies used blinded evaluators for outcomes, and 5 trials used a modified
intent-to-treat analysis. The best quality of evidence came from trials of
corticosteroids.
• The relative risk for unsatisfactory recovery for corticosteroids alone vs control
treatments was 0.69. This finding translated into a number needed to treat of 11
with corticosteroids to promote 1 more satisfactory outcome.
• Corticosteroids alone also reduced the risks for synkinesis and autonomic
dysfunction vs control treatment (relative risk, 0.48).
• The use of corticosteroids alone did not significantly increase the risk for adverse
events.
• Corticosteroid treatment with antiviral agents created a synergistic effect and
reduced the rate of unsatisfactory facial recovery (relative risk, 0.48).
• However, antiviral medications alone were not significantly different from control
treatment in rates of satisfactory facial recovery, synkinesis, autonomic
dysfunction, and adverse events.
• Corticosteroids at cumulative doses equivalent to 450 mg of prednisone or more
were associated with a greater treatment effect vs doses lower than 450 mg.
Treatment within 72 hours failed to significantly alter the therapeutic effect of
corticosteroids and antiviral agents, and there was a trend toward greater efficacy
of corticosteroids for moderate paresis vs severe paresis.
• Only corticosteroids were associated with a treatment benefit between 6 weeks
and 4 months.

Clinical Implications

• Slightly more than 70% of individuals with Bell's palsy fully recover facial nerve
function without treatment.
• The current meta-analysis suggests that corticosteroids are effective in improving
outcomes of Bell's palsy, and adding antiviral medications may make treatment
even more effective. However, antiviral agents alone do not improve Bell's palsy.