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Meta-Analysis
. 2014 Feb 6;2014(2):CD006866.
doi: 10.1002/14651858.CD006866.pub3.

Antiviral treatment for preventing postherpetic neuralgia

Ning Chen  1 , Qifu Li, Jie Yang, Muke Zhou, Dong Zhou, Li He
Affiliations
Meta-Analysis

Antiviral treatment for preventing postherpetic neuralgia

Ning Chen et al. Cochrane Database Syst Rev. .

Abstract

Background: Postherpetic neuralgia (PHN) is a painful and refractory complication of herpes zoster. Treatments are either partially or totally ineffective for many people with PHN. Antiviral agents, used at the time of the rash, have been proposed as an intervention to prevent the development of PHN. This is the first update since the first publication of the review in 2009.

Objectives: To assess the effectiveness of antiviral agents in preventing PHN.

Search methods: On 26 April 2013, we updated the searches in the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and the Chinese Biomedical Retrieval System. We checked the references of published studies to identify additional trials, and contacted authors to obtain additional data. We searched other databases in The Cochrane Library for information for the Discussion and two clinical trials registries for ongoing trials.

Selection criteria: We considered all randomised controlled trials (RCTs) of antiviral treatment given within 72 hours after the onset of herpes zoster for preventing PHN. There were no language restrictions.

Data collection and analysis: Two authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data.

Main results: Six RCTs with a total of 1211 participants were eligible; five trials evaluated oral aciclovir, and one, with 419 participants, evaluated oral famciclovir. We were able to conduct meta-analyses as there were sufficient similarities in the included studies, such as the reporting of the presence of PHN, duration of rash before treatment initiation and treatment regimen. For our primary outcome, based on three trials (609 participants) we found no significant difference between the aciclovir and control groups in the incidence of PHN four months after the onset of the acute herpetic rash (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.51 to 1.11), nor was there a significant difference at six months (RR 1.05, 95% CI 0.87 to 1.27, two trials, 476 participants). In four of the trials (692 participants), there was some evidence for a reduction in the incidence of pain four weeks after the onset of rash. In the trial of famciclovir versus placebo, neither 500 mg nor 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly. The most commonly reported adverse events were nausea, vomiting, diarrhoea and headache for aciclovir, and headache and nausea for famciclovir. For neither treatment was the incidence of adverse events significantly different from placebo. None of the studies were at high risk of bias, although the risk of bias was unclear in at least one domain for all but one study. We found no new RCTs when we updated the searches in April 2013.

Authors' conclusions: There is high quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments; therefore, further well-designed RCTs are needed to investigate famciclovir or other new antiviral agents in preventing PHN. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different subgroups of people, such as people who are immunocompromised.

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Conflict of interest statement

None known

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study. Green = low risk of bias; yellow = unclear risk of bias, red = high risk of bias (not shown).
2
2
Forest plot of comparison 1: Oral aciclovir versus placebo or no treatment, outcome 1.1 The presence of PHN 6 months after the onset of the acute herpetic rash.
3
3
Forest plot of comparison 1 Oral aciclovir versus placebo or no treatment, outcome 1.2 The presence of PHN 4 months after the onset of the acute herpetic rash.
4
4
Forest plot of comparison 1 Oral aciclovir versus placebo or no treatment, outcome 1.4 Adverse events.
5
5
Forest plot of comparison 1 Oral aciclovir versus placebo or no treatment, outcome 1.3 The presence of herpetic neuralgia 1 month after the onset of the acute herpetic rash.
6
6
Forest plot of comparison 4 Sensitivity analysis, outcome 4.1 The presence of postherpetic neuralgia.
1.1
1.1. Analysis
Comparison 1 Oral aciclovir versus placebo or no treatment, Outcome 1 Presence of PHN 6 months after the onset of the acute herpetic rash.
1.2
1.2. Analysis
Comparison 1 Oral aciclovir versus placebo or no treatment, Outcome 2 Presence of PHN 4 months after the onset of the acute herpetic rash.
1.3
1.3. Analysis
Comparison 1 Oral aciclovir versus placebo or no treatment, Outcome 3 Presence of PHN 1 month after the onset of the acute herpetic rash.
1.4
1.4. Analysis
Comparison 1 Oral aciclovir versus placebo or no treatment, Outcome 4 Adverse events.
2.1
2.1. Analysis
Comparison 2 Oral famciclovir versus placebo or no treatment, Outcome 1 Presence of PHN.
3.1
3.1. Analysis
Comparison 3 Subgroup analysis (the presence of PHN), Outcome 1 Adults 49 years of age or less.
3.2
3.2. Analysis
Comparison 3 Subgroup analysis (the presence of PHN), Outcome 2 Adults aged 50 years or more.
4.1
4.1. Analysis
Comparison 4 Sensitivity analysis, Outcome 1 Presence of PHN.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Harding 1991 {published data only}
    1. Harding SP, Porter SM. Oral acyclovir in herpes zoster ophthalmicus. Current Eye Research 1991;10(Suppl):177‐82. [PUBMED: 1864092] - PubMed
Huff 1988 {published data only}
    1. Huff JC, Bean B, Balfour HH, Laskin OL, Connor JD, Corey L, et al. Therapy of herpes zoster with oral acyclovir. American Journal of Medicine 1988;85(2A):84‐9. [PUBMED: 3044099] - PubMed
Morton 1989 {published data only}
    1. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. New Zealand Medical Journal 1989;102(863):93‐5. [PUBMED: 2648213] - PubMed
Tyring 1995 {published data only}
    1. Tyring S, Barbarash RA, Nahlik JE, Cunningham A, Marley J, Heng M, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double‐blind, placebo‐controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Annals of Internal Medicine 1995;123(2):89‐96. [PUBMED: 7778840] - PubMed
Whitley 1996 {published data only}
    1. Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG, et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo‐controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Annals of Internal Medicine 1996;125(5):376‐83. [PUBMED: 8702088] - PubMed
Wood 1988 {published data only}
    1. Wood MJ, Ogan PH, McKendrick MW, Care CD, McGill JI, Webb EM. Efficacy of oral acyclovir treatment of acute herpes zoster. American Journal of Medicine 1988;85(2A):79‐83. [PUBMED: 3044098] - PubMed

References to studies excluded from this review

Benoldi 1991 {published data only}
    1. Benoldi D, Mirizzi S, Zucchi A, Allegra F. Prevention of post‐herpetic neuralgia. Evaluation of treatment with oral prednisone, oral acyclovir, and radiotherapy. International Journal of Dermatology 1991;30(4):288‐90. - PubMed
Cobo 1986 {published data only}
    1. Cobo LM, Foulks GN, Liesegang T, Lass J, Sutphin JE, Wilhelmus K, et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalmology 1986;93(6):763‐70. - PubMed
Dekonenko 1998 {published data only}
    1. Dekonenko EP, Shishov AS, Kupriianova LV, Rudometov IuP, Bagrov FI. Neuralgia and Zovirax treatment of patients with herpes zoster. Terapevticheskii Arkhiv 1998;70(12):63‐5. [PUBMED: 10067257] - PubMed
Dekonenko 1999 {published data only}
    1. Dekonenko EP, Shishov AS, Kupriianova LV, Rudometov IuP, Bagrov FI. Postherpetic neuralgia in herpes zoster: its treatment with Zovirax. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova 1999;99(6):56‐8. [PUBMED: 10441870] - PubMed
Esmann 1982 {published data only}
    1. Esmann V, Ipsen J, Peterslund NA, Seyer‐Hansen K, Schønheyder H, Juhl H. Therapy of acute herpes zoster with acyclovir in the nonimmunocompromised host. American Journal of Medicine 1982;73(1A):320‐5. - PubMed
Galbraith 1983 {published data only}
    1. Galbraith AW. Prevention of post‐herpetic neuralgia by amantadine hydrochloride (Symmetrel). British Journal of Clinical Practice 1983;37(9):304‐6. - PubMed
Hoang‐Xuan 1992 {published data only}
    1. Hoang‐Xuan T, Büchi ER, Herbort CP, Denis J, Frot P, Thénault S, et al. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology 1992;99(7):1062‐71. - PubMed
Mandal 1988 {published data only}
    1. Mandal BK, Dunbar EM, Ellis ME, Ellis J, Dowd P. A double‐masked, placebo‐controlled trial of acyclovir cream in immunocompetent patients with herpes zoster. Journal of Infection 1988;17(2):57‐63. - PubMed
McGill 1983 {published data only}
    1. McGill J, MacDonald DR, Fall C, McKendrick GD, Copplestone A. Intravenous acyclovir in acute herpes zoster infection. Journal of Infection 1983;6(2):157‐61. - PubMed
Mondelli 1996 {published data only}
    1. Mondelli M, Romano C, Passero S, Porta PD, Rossi A. Effects of acyclovir on sensory axonal neuropathy, segmental motor paresis and postherpetic neuralgia in herpes zoster patients. European Neurology 1996;36(5):288‐92. - PubMed
Payne 1989 {published data only}
    1. Payne CM, Menday AP, Rogers T, Staughton RC. Isoprinosine does not influence the natural history of herpes zoster or postherpetic neuralgia. Scandinavian Journal of Infectious Diseases 1989;21(1):15‐8. - PubMed
van der Broek 1984 {published data only}
    1. Broek PJ, Meer JW, Mulder JD, Versteeg J, Mattie H. Limited value of acyclovir in the treatment of uncomplicated herpes zoster: a placebo controlled study. Infection 1984;12(5):338‐41. - PubMed
Varotti 2001 {published data only}
    1. Varotti C, Rafanelli A. Evaluation of efficacy and tolerance of neuramide in the treatment of herpes zoster and postherpetic neuritis. Drugs under Experimental and Clinical Research 2001;27(5‐6):199‐208. [PUBMED: 11951578] - PubMed
Wassilew 1987 {published data only}
    1. Wassilew SW, Reimlinger S, Nasemann T, Jones D. Oral acyclovir for herpes zoster: a double‐blind controlled trial in normal subjects. British Journal of Dermatology 1987;117(4):495‐501. - PubMed
Wood 1994 {published data only}
    1. Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. New England Journal of Medicine 1994;330(13):896‐900. - PubMed

Additional references

Alper 2000
    1. Alper BS, Lewis PR. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia?. Journal of Family Practice 2000;49(3):255‐64. - PubMed
Anonymous 1998
    1. Anonymous. Famciclovir: slightly helpful in herpes zoster. Prescrire International 1998;35(7):81‐2. - PubMed
Attal 2006
    1. Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, et al. EFNS Task Force. EFNS guidelines on pharmacological treatment of neuropathic pain. European Journal of Neurology 2006;13(11):1153‐69. - PubMed
Chen 2011
    1. Chen N, Li Q, Zhang Y, Zhou M, Zhou D, He L. Vaccination for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD007795.pub2] - DOI - PubMed
Crooks 1991
    1. Crooks RJ, Jones DA, Fiddian AP. Zoster‐associated chronic pain: an overview of clinical trials with acyclovir. Scandinavian Journal of Infectious Diseases 1991;80(Suppl):62‐8. - PubMed
Desmond 2002
    1. Desmond RA, Weiss HL, Arani RB, Soong SJ, Wood MJ, Fiddian PA, et al. Clinical applications for change‐point analysis of herpes zoster pain. Journal of Pain and Symptom Management. 2002;23(6):510‐6. - PubMed
Dubinsky 2004
    1. Dubinsky RM, Kabbani H, El‐Chami Z, Boutwell C, Ali H, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of postherpetic neuralgia: an evidence‐based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004;63(6):959‐65. - PubMed
Dworkin 1994
    1. Dworkin RH, Portenoy RK. Proposed classification of herpes zoster pain. Lancet 1994;343(8913):1648. - PubMed
Dworkin 2001
    1. Dworkin RH, Schmader KE. Epidemiology and natural history of herpes zoster and postherpetic neuralgia. Herpes zoster and postherpetic neuralgia. 2nd Edition. New York: Elsevier Press, 2001:39‐64.
Fillet 2002
    1. Fillet AM. Prophylaxis of herpesvirus infections in immunocompetent and immunocompromised older patients. Drugs & Aging 2002;19(5):343‐54. - PubMed
Gnann 2002
    1. Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. New England Journal of Medicine 2002;347(5):340‐6. - PubMed
GRADE working group 2004
    1. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490‐4. - PMC - PubMed
Griffin 1998
    1. Griffin MJ, Chambers FA, MacSullivan R. Post herpetic neuralgia: a review. Irish Journal of Medical Science 1998;167(2):74‐8. - PubMed
Han 2013
    1. Han Y, Zhang J, Chen N, He L, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2013, Issue 3. [DOI: 10.1002/14651858.CD005582.pub4] - DOI - PubMed
Hempenstall 2005
    1. Hempenstall K, Nurmikko TJ, Johnson RW, A'Hern RP, Rice AS. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Medicine/Public Library of Science 2005;2(7):e164. - PMC - PubMed
Higgins 2002
    1. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statistics in Medicine 2002;21(11):1539‐58. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. British Medical Journal 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011a
    1. Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Intervention Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. [Available from www.cochrane‐handbook.org.]
Higgins 2011b
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. [Available from www.cochrane‐handbook.org.]
ICHEWG 2007
    1. Intemational Conference on Harmonisation Expert Working Group. International conference on harmonisation of technical requirements for registration of Pharmaceuticals for human use adopts Consolidated Guideline on Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. International Digest of Health Legislation. 1997; Vol. 48:231‐4. - PubMed
Jackson 1997
    1. Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta‐analysis. Archives of Internal Medicine 1997;157(8):909‐12. - PubMed
Khaliq 2007
    1. Khaliq W, Alam S, Puri NK. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD004846.pub2] - DOI - PubMed
Kost 1996
    1. Kost RG, Straus SE. Postherpetic neuralgia ‐ pathogenesis, treatment, and prevention. The New England Journal of Medicine 1996;335(1):32‐42. - PubMed
Lancaster 1995
    1. Lancaster T, Silagy C, Gray S. Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials. British Journal of General Practice 1995;45(390):39‐45. - PMC - PubMed
Mahalingam 1995
    1. Mahalingam R, Wellish M, Brucklier J, Gilden DH. Persistence of varicella‐zoster virus DNA in elderly patients with postherpetic neuralgia. Journal of Neurovirology 1995;1(1):130‐3. - PubMed
McKendrick 1986
    1. McKendrick MW, McGill JI, White JE, Wood MJ. Oral acyclovir in acute herpes zoster. British Medical Journal 1986;293:1529‐32. - PMC - PubMed
Oxman 2005
    1. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. New England Journal of Medicine 2005;352(22):2271‐84. - PubMed
Portenoy 1986
    1. Portenoy RK, Duma C, Foley KM. Acute herpetic and postherpetic neuralgia: clinical review and current management. Annals of Neurology 1986;20(6):651‐64. - PubMed
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Schmader 2002
    1. Schmader KE. Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy. The Clinical Journal of Pain 2002;18(6):350‐4. - PubMed
Schünemann 2011a
    1. Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and 'Summary of findings' tables. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Schünemann 2011b
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Smith 1978
    1. Smith FP. Pathological studies of spinal nerve ganglia in relation to intractable intercostal pain. Surgical Neurology 1978;10(1):50‐3. - PubMed
Stankus 2000
    1. Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. American Family Physician 2000;61(8):2437‐44, 2447‐8. - PubMed
Stratton Hill 1997
    1. Stratton Hill C. Guidelines for Treatment of Cancer Pain: The Revised Pocket Edition of the Final Report of the Texas Cancer Council's Workgroup on Pain Control in Cancer Patients. 2nd Edition edition. Texas Cancer Council, 1997.. Guidelines for Treatment of Cancer Pain: The Revised Pocket Edition of the Final Report of the Texas Cancer Council's Workgroup on Pain Control in Cancer Patients. 2nd Edition. Texas Cancer Council, 1997.
Thyregod 2007
    1. Thyregod HG, Rowbotham MC, Peters M, Possehn J, Berro M, Petersen KL. Natural history of pain following herpes zoster. Pain 2007;128(1‐2):148‐56. - PMC - PubMed
Vafai 1988
    1. Vafai A, Wellish M, Gilden DH. Expression of varicella‐zoster virus in blood mononuclear cells of patients with postherpetic neuralgia. Proceedings of the National Academy of Sciences of the United States of America 1988;85(8):2767‐70. - PMC - PubMed
Wang 2009
    1. Wang P, Zhao J, Wu T. Acupuncture for postherpetic neuralgia. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD007793] - DOI
Ware 1998
    1. Ware JE, Gandek B. Overview of the SF‐36 Health‐Survey and the International Quality of Life Assesment (IQOLA) Project. Journal of Clinical Epidemiology 1998;51(11):903‐12. - PubMed
Watson 1991
    1. Ware JE, Gandek B. Overview of the SF‐36 Health‐Survey and the International Quality of Life Assesment (IQOLA) Project. Journal of Clinical Epidemiology 1998;51(11):903‐12. - PubMed
Wood 1996
    1. Wood MJ, Kay R, Dworkin RH, Soong SJ, Whitley RJ. Oral acyclovir therapy accelerates pain resolution in patients with herpes zoster: a meta‐analysis of placebo‐controlled trials. Clinical Infectious Diseases 1996;22(2):341‐7. - PubMed

References to other published versions of this review

Li 2007
    1. Li Q, He L, Zhang Q, Zhou M, Zhou D. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006866] - DOI
Li 2009
    1. Li Q, Chen N, Yang J, Zhou M, Zhou D, Zhang Q, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD006866.pub2] - DOI - PubMed

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