Practice Parameter: Treatment of Postherpetic Neuralgia

Transcript Practice Parameter: Treatment of Postherpetic Neuralgia

Practice Parameter: Treatment of Postherpetic Neuralgia

An Evidence Based Report of the QSS of the American Academy of Neurology Richard M. Dubinsky, MD; Haidar Kabbani, MD; Ziad El Chami, MD; Christine Boutwell, MD; and Hassim Ali, M.D.

Published in

Neurology

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Objective of the guideline

To determine which treatments provide benefit in terms of decreased pain and improved quality of life in patients with postherpetic neuralgia.

Methods of evidence review

• Searched Medline database and the Cochrane database for: – peer reviewed articles – published between 1960 and August, 2003, updating in January, 2004 – using MESH terms herpes zoster/*complications and neuralgia/*treatment • Reviewed titles and abstracts of these articles, for interventions that decrease the pain of postherpetic neuralgia © 2004 American Academy of Neurology February 25, 2004

Methods of evidence review

Inclusion criteria: • Alleviation of pain in postherpetic neuralgia, of at least 8 weeks after healing of the herpetic rash • Prospective, retrospective, or case series studies with clinical information on the subjects who received treatment © 2004 American Academy of Neurology February 25, 2004

Methods of evidence review

Inclusion criteria: • Detailed methodology and clear outcome measure • Demonstrate a decrease of pain related to postherpetic neuralgia • Treatment was feasible for an outpatient setting © 2004 American Academy of Neurology February 25, 2004

Methods of evidence review

• 206 articles met original Medline search criteria: – 111 articles regarding the treatment of postherpetic neuralgia were reviewed in their entirety – 42 met the predefined inclusion criteria – 9 additional articles were found by searching bibliographies of review articles and by searching Medline using names of primary authors in the original search © 2004 American Academy of Neurology February 25, 2004

AAN Strength of evidence

Class I

Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required: •primary outcome(s) is/are clearly defined •exclusion/inclusion criteria are clearly defined •adequate accounting for drop-outs and cross-overs with numbers sufficiently low to have minimal potential for bias •relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences © 2004 American Academy of Neurology February 25, 2004

AAN Strength of evidence

Class II Class III Class IV

Prospective matched group cohort study in a representative population with masked outcome assessment that meets a-d above OR a RCT in a representative population that lacks one criteria a-d. All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment. Evidence from uncontrolled studies, case series, case reports, or expert opinion © 2004 American Academy of Neurology February 25, 2004

AAN Translation of evidence to level of recommendation

Level A

Level A rating requires at least one convincing class I study or at least two consistent, convincing class II studies. Established as effective, ineffective, or harmful for the given condition in the specified population.

Level B

Level B rating requires at least one convincing class II study or at least three consistent class III studies. Probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population.

AAN Translation of evidence to level of recommendation

Level C Level U

Level C rating requires at least two convincing and consistent class III studies. Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. Data inadequate or conflicting. Given current knowledge, treatment is unproven. © 2004 American Academy of Neurology February 25, 2004

Introduction

Acute herpetic neuralgia – Associated with the outbreak of a herpes zoster rash – Characterized by: • Burning • Aching • Electric shock like pain • Unbearable itching – Pain may precede the onset of the herpetic rash – Often herpetic neuralgia occurs with the development of a rash © 2004 American Academy of Neurology February 25, 2004

Introduction

Postherpetic neuralgia – Persistence of the pain of herpes zoster more than three months after resolution of the rash – Clinical case definition of Postherpetic neuralgia varies from one to six months after resolution of the rash – Zoster-associated pain describes the range of pain from acute herpes zoster to the development of postherpetic neuralgia – Duration of postherpetic neuralgia is highly variable © 2004 American Academy of Neurology February 25, 2004

Introduction

Clinical question

In patients with postherpetic neuralgia, which treatments provide benefit in terms of decreased pain and improved quality of life?

Tricyclic antidepressants

Class I and II Evidence

Author, Year Watson, 1992 Watson, 1982 I Level of Evidence II Intervention • Amtriptyline vs. maprotiline • Double blind, randomized, crossover • Amitriptyline • Double blind, randomized, cross over *AAR=absolute risk reduction ** NNT=number needed to treat © 2004 American Academy of Neurology Results ARR* / NNT** Benefit found for both treatment (AT > MT) compared to baseline Significant benefit for amitriptyline ARR=62.5% NNT=1.6 February 25, 2004

Class I and II Evidence

Author, Year Level of Evidence Max, 1988 II Intervention Kishore Kumar, 1990 II • Amitriptyline, lorazepam, and placebo • Double blind, randomized, crossover • Despiramine vs. benzotropine as active placebo • Double blind randomized study © 2004 American Academy of Neurology Results ARR / NNT • 41 completed both arms • Amitriptyline has improvement over lorazepam and placebo ARR=53% NNT=1.9 February 25, 2004

Class I and II Evidence

Author, Year Watson, 1998 Level of Evidence II Intervention • Amitriptyline vs. Nortriptyline • Double blind, randomized, crossover Results ARR / NNT • 21 had similar benefit on AT and NT • 5 on AT and 4 on NT had response to one, but not the other © 2004 American Academy of Neurology February 25, 2004

Conclusion

Based upon class I and class II evidence, the tricyclic antidepressants, amitriptyline, nortriptyline, maprotiline and desipramine are effective in lessening the pain of postherpetic neuralgia. © 2004 American Academy of Neurology February 25, 2004

Antiepileptic Drugs

February 25, 2004

Class I and II Evidence Author, Year Rowbotham, 1998 Level of Evidence I Intervention • Gabapentin up to 3600 mg/d vs. placebo • Double blind, randomized Results ARR / NNT • Decrease of 2.1 on Gabapentin, 0.5 placebo. • Based on global perception of change 66/94 improved on gabapentin, 25/79 on placebo ARR=46.2% NNT=2 © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence Author, Year Max, 1988 (also TCA) Level of Evidence Intervention II • Amitriptyline, lorazepam, and placebo • Double blind, randomized, crossover Results ARR / NNT • 41 completed both arms • Amitriptyline had greater improvement over lorazepam and placebo © 2004 American Academy of Neurology February 25, 2004

Conclusion

• Based upon two class I studies of gabapentin and a single class I study of pregabalin these antiepileptic drugs are of benefit in the reduction of pain from postherpetic neuralgia.

• Data are insufficient to reach a conclusion on the use of carbamazepine.

Opioids

February 25, 2004

Class I and II Evidence Author, Year Rowbotham, 1991 Watson, 1998 Level of Evidence I I Intervention Results ARR / NNT MS 0.3mg/kg vs. lidocaine 5mg/kg vs. placebo • Oxycodone vs. placebo • Double blind, randomized, two way cross over • 11 chose MS as providing the most relief • 4 lidocaine • 1 saline • 3 reported no benefit • 38 completed study.

Class I and II Evidence Author, Year Max, 1988 Level of Evidence II Intervention • Clonidine 0.2mg, codeine 120mg, ibuprofen 800mg, placebo • Double blind, randomized Results ARR / NNT • Benefit only for clonidine over the rest. • Significant adverse effects rate. © 2004 American Academy of Neurology February 25, 2004

Conclusion

There is class I evidence that long acting oral opioid preparations and class II evidence that tramadol provide relief in treatment of postherpetic neuralgia.

Topical and Intradermal Agents

Class I and II Evidence: Anti-inflammatory agents Author, Year Tajti, 1999 McQuay, 1990 Level of Evidence I II Intervention ASA in ointment vs. lidocaine in ointment • Benzydamine cream (a topical NSAI) vs. placebo • Double blind Results ARR / NNT Benefit for both compared to baseline (20 vs. 2 for ASA and 15 vs. 3 for lidocaine) No benefit © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence Capsaicin Author, Year Level of Evidence Watson,1993 I Intervention 0.075% capsaicin vs. placebo Results ARR / NNT • Benefit for capsaicin vs. placebo during 6 week study. • Benefit maintained for 77 subjects in 2 year follow-up ARR=31.5% NNT=3.2 © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence Topical anesthetics Author, Year Rowbotham, 1995 Level of Evidence I Intervention • Lidocaine base 5% in gel vehicle, covered with occlusive dressing vs. placebo • Double blind, randomized, cross over Results ARR / NNT • No significant relief for cranial PHN, • Significant decrease in VAS by 14mm at 8 hours for torso – limb PHN © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence Topical anesthetics Author, Year Rowbotham, 1996 Level of Evidence I Intervention • Lidocaine 5% in non-woven polyethylene patch • Double blind randomized, cross over Results ARR / NNT • Pain relief by 12.3mm on visual analog scale • 24 had from slight to complete relief © 2004 American Academy of Neurology February 25, 2004

Class I and II EvidenceTopical anesthetics: Author, Year Galer, 1999 Level of Evidence I Intervention • Lidocaine patches vs. placebo • Enriched population, double blind, randomized Results ARR / NNT • >14 D for lidocaine • 3.8 D for placebo • 91% reported benefit on lidocaine vs. 41 on placebo NNT = 2 © 2004 American Academy of Neurology February 25, 2004

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Conclusion

Based upon class I evidence topical lidocaine is effective in reducing the pain of postherpetic neuralgia. • Based on class II and class III evidence aspirin in ointment or cream, is probably effective in reducing the pain of postherpetic neuralgia. • The magnitude of benefit for topical capsaicin and for aspirin in cream is below the level that is considered clinically important in treatment of chronic pain. © 2004 American Academy of Neurology February 25, 2004

NMDA antagonist

February 25, 2004

Class I and II Evidence NMDA antagonist

Author, Year Nelson, 1997 Level of Evidence I Intervention dextromethorphan vs. placebo Results ARR / NNT • 5 reported benefit for DM • 3 for placebo • (5 could not complete study due to sedation) ARR 15.4% NNT = 65 © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence NMDA antagonist

Author, Year Eide, 1994 Level of Evidence II Intervention Ketamine 0.15mg/kg vs. MS 0.075 mg/kg vs. saline Results ARR / NNT • 6 improved with ketamine vs. 4 with MS © 2004 American Academy of Neurology February 25, 2004

Conclusion

• There are single class II studies with evidence for the lack of efficacy of the NMDA antagonists dextromethorphan and memantine in treatment of postherpetic neuralgia. © 2004 American Academy of Neurology February 25, 2004

Other modalities

February 25, 2004

Class I and II Evidence: Other Modalities

Author, Year Kotani, 2000 Level of Evidence I Intervention Intrathecal methylprednisolone plus lidocaine vs. intrathecal lidocaine vs. no treatment Results ARR / NNT Long lasting benefit for methylprednisolone and lidocaine, compared to lidocaine ARR of 75.6% NNT = 1.3 © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence Other Modalities

Author, Year Kikuchi, 1999 Level of Evidence II Intervention • Intrathecal vs. epidural methylprednisolone • 4 sessions at 1 week intervals Results ARR / NNT • At 24 weeks substantial benefit for intrathecal • Not for epidural NNT = 1.4 © 2004 American Academy of Neurology February 25, 2004

Class I and II Evidence

Author, Year Lewith, 1983 Level of Evidence II Intervention • Acupuncture vs. mock transcutaneous electrical stimulation • Single blind, randomized Results ARR / NNT • High drop out rate • No difference between the groups © 2004 American Academy of Neurology February 25, 2004

Conclusion

• Based on single class I and II studies intrathecal methylprednisolone was effective in reducing the pain of postherpetic neuralgia. • Due to invasive nature of this treatment, potential for arachnoiditis, and difficulty in obtaining preservative free methylprednisolone, it should be considered only after agents noted above have been tried and failed. © 2004 American Academy of Neurology February 25, 2004

Conclusion

Recommendations

• The following are effective and should be used in the treatment of postherpetic neuralgia (

Level A, Class I and II

– Gabapentin – Pregabalin – Opioids ): – Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine and maprotiline) – Topical lidocaine patches © 2004 American Academy of Neurology February 25, 2004

Recommendations

• There is limited evidence to support nortriptyline over amitriptyline, (

Level B, single Class II study

) and the data are insufficient to recommend one opioid over another. • Amitriptyline has significant cardiac effects in the elderly when compared to notriptyline and desipramine. © 2004 American Academy of Neurology February 25, 2004

Recommendations

• Aspirin in cream is possibly effective in the relief of pain in patients with postherpetic neuralgia, (

Level C, Class II and III

) but the magnitude of benefit is low, as is seen with capsaicin (

Level A, Class I and II

). • In countries where preservative-free intrathecal methylprednisolone is available, it may be considered in the treatment of post herpetic neuralgia (

Level A, Class I and II

Recommendations

The following treatments are not of benefit (

Level B, Class II

): – Acupuncture – Benzydamine cream – Dextromethorphan – Indomethacin – Epidural methylprednisolone – Epidural morphine sulfate – Lontophoresis of vincristine – Lorazepam – Vitamin E – Zimelidine © 2004 American Academy of Neurology February 25, 2004

Recommendations

The effectiveness of the following treatments for postherpetic neuralgia are unproven: (

Level U, single Class II study and Class IV studies

) –Carbamazepine –Nicardepine –Biperiden –Chlorprothixene –Ketamine –He: Ne laser irradiation –Intralesional triamcinolone –Cryocautery –Topical piroxicam –Extract of

Ganoderma lucidum

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Recommendations

There is insufficient evidence at this time to make any recommendations on the long-term effects of these treatments.

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Future Research

Further areas for research in treatment of postherpetic neuralgia should expand upon: – Variety of treatments – – Natural history of postherpetic neuralgia Response of the various components of the pain of postherpetic neuralgia (dysesthesias, paresthesias, hyperalgesia, hyperesthesia, and allodynia) to treatment Contribution of evoked pain in the outcomes assessment of treatment of postherpetic neuralgia.

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Future Research

The case definition of postherpetic neuralgia has changed, with a trend towards a longer duration of symptoms required to distinguish postherpetic neuralgia from acute herpetic neuralgia. This is a major confounder in any attempt to generalize the results of many studies. © 2004 American Academy of Neurology February 25, 2004

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Future Research

Direct comparison studies of topical and oral agents are needed. Research into use of combinations of therapies, and therapies aimed at disease modification needs to be addressed. Long-term efficacy of treatments of postherpetic neuralgia must be compared to the natural history for resolution of postherpetic neuralgia.

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Practice Parameter: Treatment of Postherpetic Neuralgia

Transcript Practice Parameter: Treatment of Postherpetic Neuralgia