Aimee Dawson MPH, DMD; Tamara Wright BSc, MSc, DMD, Dip Perio
Evidence showed no significant benefit from anti-herpes simplex viral agents alone as compared with placebo in producing complete recovery from Bell’s palsy.
Although combined therapy using antivirals and corticosteroids were more likely to effect complete recovery than placebo treatment for Bell’s palsy, treatment with antivirals alone does not appear to have any benefit over placebo treatment.
For patients with Bell's palsy, does treatment with antiviral agents decrease risk for incomplete recovery and does treatment with antivirals plus corticosteroids further decrease the risk for incomplete recovery over treatment with corticosteroids alone?
The researchers searched four electronic databases to December 2008 for randomized and quasi-randomized controlled trials involving anti-herpes simplex antiviral medication alone or in combination with corticosteroid therapy in treatment of Bell’s palsy. Non-English papers were included. Each paper was independently assessed by at least two authors for relevance, eligibility and quality, with 100 percent agreement among authors for inclusion. The primary outcome measure was risk for incomplete recovery of facial function by the end of the trial, as defined by a validated rating scale. Risk of bias was completed using the 2008 Cochrane criteria. In combining the data, the authors used a random effects model where marked heterogeneity existed among studies (Chi2 test,P < 0.1, I2 > 50 percent). They used a fixed-effect model when heterogeneity was undetected with standard statistical methods. Sensitivity analysis was performed both to investigate whether the conclusions were altered when studies with a follow-up of less than six months were excluded and to assess the differing response to aciclovir and valaciclovir.
The review identified 97 papers of which seven trials (1,987 participants) met the inclusion criteria. The authors found no statistically significant inrease in the rate of incomplete recovery from anti-herpes simplex antiviral therapy as compared with placebo, including comparisons in which corticosteroids were given to both groups (n=1886, relative risk (RR) 0.88, 95 percent confident interval (CI) 0.65 to 1.18). The outcome for antivirals plus corticosteroid therapy was significantly better compared to placebo (n=658, RR 0.56, 95 percent CI 0.41 to 0.76). The risk for incomplete recovery for anti-herpes simplex antivirals alone versus placebo or no treatment was not statistically significant (n = 658, RR 1.14 (95% CI 0.80 to 1.62). Neither increasing the duration of follow-up to six months nor using different antiviral drugs significantly affected the results.
No significant benefit resulted from treatment with anti-herpes simplex antivirals compared with placebo in producing complete recovery from Bell's palsy and they were less likely than corticosteroids to produce complete recovery.
Source of Funding:
University of Dundee, UK
Importance and Context:
Bell’s palsy, an acute unilateral facial paralysis, is a common neurological condition of unknown etiology. About 30 percent of people with Bell's palsy do not recover completely (1), which underscores the importance of investigating the most effective treatment modalities in this review. Antiviral therapy commonly is prescribed to treat Bell’s palsy based on an assumption that herpes simplex may be implicated in this condition. In 2009 two systemic review articles (4, 5) compared corticosteroid treatment alone with corticosteroid plus antiviral treatment for Bell's palsy. Their published findings conflicted, with one review suggesting that combination treatment improved the rate of full recovery while the second did not. The contradictory findings of those reviews and of this one suggest that more research is needed into the role viral infection plays in the etiology of Bell's palsy.
Strengths and Weaknesses of the Systematic Review:
This is an update of a review published in 2001 (3) with relaxed inclusion criteria compared to the previous search. The focus of this review, however, was not to evaluate corticosteroid therapy, a topic which has been considered fully in another recent Cochrane Collaboration systematic review (2). The authors conducted a rigorous review but there was inconsistency in the editing of this paper, with respect to inclusion of corticosteroids in the intervention and comparison treatment, which made the review difficult to interpret. Their search methodology was thorough and they assessed risk-of-bias using accepted criteria. They performed sensitivity analysis to investigate how time and type of antivirals affected outcome and appropriately addressed heterogeneity.
Strengths and Weaknesses of the Evidence:
The number of randomized controlled trials included in this review was increased over the earlier review by broadening the inclusion criteria. Two large trials (n=1,480) were at low risk of bias. The addition of five studies at high risk of bias resulted in significant heterogeneity which could not be accounted for statistically. Inclusion of the results of the studies at high risk of bias did not change the overall conclusions. All trials reported different lengths of follow-up (3 to 12 months). Adverse events were reported in three trials, with no difference in rates between antivirals versus placebo.
Implications for Dental Practice:
Patients with acute onset of unilateral facial paralysis may seek treatment from a dentist. Antiviral therapy commonly is prescribed to treat this condition based on the hypothesis that its etiology involves the herpes simplex virus. In this review there is limited quality evidence to show that antivirals alone had no significant benefit versus placebo or no treatment. The combination of antivirals and corticosteroids did, however, appear to improve a patient's chance of complete recovery from Bell's palsy. Other systematic reviews present conflicting conclusions about combination therapy. This discrepancy supports the need for further investigation into the role viral infection plays in the etiology of Bell’s palsy.
1. Morgenlander JC, Massey EW. Bell's Palsy: ensuring the best possible outcome. Postgraduate Medicine 1990; 88(5)
2. Salinas RA, Alvarez G, Daly F, Ferreira J. Corticosteroids for Bell's Palsy (idiopathic facial paralysis). Cochrane Database of Systematic Reviews (online) 2010; 3: CD001942.
3. Salinas RA, Alvarez MI, Ferreira J. Corticosteroids for Bell's palsy (idiopathic facial paralysis). Cochrane Database of Systematic Reviews 2002, Issue 2.
4. de Almeida JR, Al Khabori M, Guyatt GH, Witterick IJ, Lin VY, Nedzelski JM, Chen JM. Combined corticosteroid and antiviral treatment for Bell Palsy: a systematic review and meta-analysis. JAMA 2009; 302(9): 985-993.
5. Goudakos JK, Konstantinos D, Markou D. Corticosteroids vs Corticosteroids Plus Antiviral Agents in the Treatment of Bell Palsy: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg 2009; 135 (6): 558-564.