Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
XXIXXIII
NO 1
JUNE
2013 2015
VOL
NO
4 MAY
Editorial
Boardneuralgia (PHN)
ostherpetic
Michael C. Rowbotham, MD
California Pacific Medical Center
Research Institute
Department of Anesthesia,
UCSF School of Medicine
San Francisco, Calif., USA
Email: rowbotm@cpmcri.org
PAIN: CLINICAL UPDATES MAY 2015
June2013
Antiviral Agents
Pharmacotherapy of Acute
Herpes Zoster
The treatment of HZ aims to limit the
duration and severity of the attack,
relieve symptoms, and prevent complications. All patients should receive
a medical and psychosocial history
evaluation and targeted physical
examination to confirm the diagnosis,
document comorbid illnesses, and
provide a basis for treatment.
Treatment of Postherpetic
Neuralgia
The efficacy of current treatments is
still far from satisfactory. PHN is a classical model to test the efficacy of potential new drugs for neuropathic pain. A
global database of all registered PHN
trials and results (if any are available)
has been reported28 and was updated in
mid-2014.29,30 The database is available
as part the Repository of Registered
Analgesic Clinical Trials (RReACT)
through the ACTTION website (http://
www.acttion.org/). Of 112 unique registered trials, 66 were reported as completed. Only 20 completed trials had
results available in the peer-reviewed
literature, and another 17 had results
available via the gray literature or
posted on a trials registry. In addition to
the lack of results from a large proportion of completed trials, some important
clinical issues have not been tested in a
clinical trial. For example, none of the
available serotonin and norepinephrine
reuptake inhibitors (SNRIs) have been
studied for PHN.
Numerous meta-analyses and
treatment guidelines have been published. A PHN-specific meta-analysis
was published in 2005,31 but recommendations provided here are largely based
on analyses from 2014 and 2015.1,32
Tricyclic antidepressants (TCAs),
gabapentinoids, opioids, and topical capsaicin have strong evidence
Editorial Board
Editor-in-Chief
M.R. Rajagopal, MD
Pain Medicine, Palliative Medicine
India
Claudia Sommer, MD
Neurology
Germany
Table I
Studies on evidence of TCAs, gabapentinoids, opioids, and topical capsaicin for postherpetic neuralgia
showing positive (P) or negative (N) outcomes
Drug, Maximal Daily Dose
Outcome
Number
Randomized
Duration
Amitriptyline, average 73 mg
24
3 weeks
Amitriptyline, average 65 mg
62
6 weeks
Amitriptyline, 200 mg
NA
24/49
8 weeks
Desipramine, 250 mg
26
6 weeks
76
8 weeks
Pregabalin, 600 mg
173
8 weeks
157/238
8 weeks
281/370
13 weeks
270
4 weeks
Gabapentin, 3600 mg
229
8 weeks
334
7 weeks
407
10 weeks
452
10 weeks
P twice daily;
N once daily
158
4 weeks
NCT00619476
ClinTrials.gov
376
13 weeks
Tramadol, 400 mg
127
6 weeks
Oxycodone, 60 mg
50
4 weeks
76
8 weeks
402
12 weeks
38
4 weeks
418
12 weeks
299
12 weeks
155
12 weeks
Capsaicin, 0.075%
32
6 weeks
Capsaicin, 0.075%
143
6 weeks
Study
TCAs
PREGABALIN
GABAPENTIN
GABAPENTIN ER or ENACARBIL
TRAMADOL
Boureau et al. 2003
OPIOIDS
CAPSAICIN 8%
CAPSAICIN CREAM
Table 2
Mechanisms of action and dosing of systemic drugs for neuropathic pain
Medication
Maximum Recommended
Dose
Mechanism of Action
Starting Dose
Titration
1025 mg at
bedtime
Gabapentin
100300 mg at
bedtime
Increase by
100300 mg
three times daily
every 17 days
Pregabalin
75 mg twice
daily
Increase to 300
mg daily after 37
days, then by 150
mg/d every 37
days
Tramadol
50 mg once or
twice daily
Increase by
50100 mg daily
in divided doses
every 37 days as
tolerated
Oxycodone CR
10 mg twice
daily
Increase by 20
mg daily or more
slowly as tolerated
TCAs
Nortriptyline, desipramine,
(amitriptyline, imipramine)1
Gabapentinoids
Opioid Agonists
Prevention of Postherpetic
Neuralgia
The only well-documented means of preventing PHN is the prevention of HZ. A
live attenuated VZV vaccine is approved
for immunocompetent persons of age 50
years or older. The Shingles Prevention
Study, which included people 60 years or
older, showed that the vaccine reduced
the incidence of HZ by 51% and the incidence of PHN by 66%.7 A much smaller
study involving persons 50 to 59 years of
age showed that vaccination reduced the
incidence of HZ by 70%.42 A long-term
persistence substudy showed that vaccine efficacy decreased from 51% to 21%
for incidence of HZ and from 66% to 35%
for incidence of PHN from 7 through
11 years post-vaccination. Statistically
significant vaccine efficacy for incidence
of HZ persisted only through year 8.43
Cost-effectiveness analyses of the zoster
vaccine have estimated the cost of a quality-adjusted life year from US$10,000 to
more than US$100,000 depending on assumptions regarding duration of vaccine
protection and the magnitude of the loss
in quality of life associated with HZ and
PHN.3 In the United Kingdom, researchers estimated that vaccination at either
65 or 70 years is the most cost-effective,20
whereas a German study concluded
Conclusion
HZ and PHN present challenges to
health care systems, as they are prevalent, cause suffering and impaired
function, and are difficult to treat satisfactorily, especially in societies with
aging populations. The optimal use of
the current therapies by tailoring the
treatment individually, monitoring the
patients to assess efficacy, tolerability,
and functional status, and providing support in psychosocial aspects
when needed may improve the results.
Zoster vaccine is available to prevent
zoster, and new compounds to treat
PHN are awaited.
Conflicts of Interest
Maija Haanp has been a member of
the advisory boards of Abbvie, Allergan, Astellas, Eli Lilly, Janssen Cilag,
Pfizer, and Sanofi-Aventis. International congress attendance (registration
References
1. Johnson RW, Rice AS. Clinical practice. Postherpetic neuralgia. N Engl J
Med 2014;371:152633.
2. Yawn BP, Gilden D. The global epidemiology of herpes zoster. Neurology
2013;81:92830.
3. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence
and complications of herpes zoster: towards a global perspective. BMJ Open
2014;4:e004833.
4. Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A
population-based study of the incidence and complication rates of herpes
zoster before zoster vaccine introduction. Mayo Clin Proc 2007;82:13419.
5. Gauthier A, Breuer J, Carrington D, Martin M, Rmy V. Epidemiology
and cost of herpes zoster and post-herpetic neuralgia in the United Kingdom.
Epidemiol Infect 2009;137:3847.
6. van Wijck AJ, Opstelten W, Moons KG, van Essen GA, Stolker RJ, Kalkman CJ, Verheij TJ. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial. Lancet
2006;367:21924.
7. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD,
Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman
KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli
JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF,
Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton
DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS,
Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin
MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber
JL; Shingles Prevention Study Group. A vaccine to prevent herpes zoster and
postherpetic neuralgia in older adults. N Engl J Med 2005;352:227184.
8. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic
pain in the general population: a systematic review of epidemiological studies.
Pain 2014;155:65462.
9. Haanp M, Laippala P, Nurmikko T. Allodynia and pinprick hypoaesthesia
in acute herpes zoster predict the development of postherpetic neuralgia. J
Pain Symptom Manage 2000;20:50
10. Petersen KL, Rowbotham MC. Natural history of sensory function after
herpes zoster. Pain 2010;150:8392.
11. Boogaard S, De Vet HC, Faber CG, Zuurmond WW, Perez RS. An overview of predictors for persistent neuropathic pain. Expert Rev Neurother
2013;13:50513.
12. Watson CP, Deck JH, Morshead C, Van der Kooy D, Evans RJ. Post-herpetic
neuralgia: further post-mortem studies of cases with and without pain. Pain
1991;44:10517.
13. Johnson RW, Bouhassira D, Kassianos G, Leplge A, Schmader KE, Weinke
T. The impact of herpes zoster and post-herpetic neuralgia on quality-of-life.
BMC Med 2010;8:37.
14. Petersen KL, Rowbotham MC. Natural history of sensory function after
herpes zoster. Pain 2010;150:8392.
15. Petersen KL, Rice FL, Farhadi M, Reda H, Rowbotham MC. Natural history
of cutaneous innervation following herpes zoster. Pain 2010;150:7582.
16. Reda H, Greene K, Rice FL, Rowbotham MC, Petersen KL. Natural history
of herpes zoster: late follow-up of 3.9 years (n = 43) and 7.7 years (n = 10). Pain
2013;154:222733.
17. Bouhassira D, Chassany O, Gaillat J, Hanslik T, Launay O, Mann C, Rabaud
C, Rogeaux O, Strady C. Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in
general practice. Pain 2012;153:3429.
18. Drolet M, Brisson M, Schmader KE, Levin MJ, Johnson R, Oxman MN,
Patrick D, Blanchette C, Mansi JA. The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study. CMAJ
2010;182:17316.
19. Daniel HC, Narewska J, Serpell M, Hoggart B, Johnson R, Rice AS.
Comparison of psychological and physical function in neuropathic pain and
nociceptive pain: implications for cognitive behavioral pain management
programs. Eur J Pain 2008;12:73141.
20. van Hoek AJ, Gay N, Melegaro A, Opstelten W, Edmunds WJ. Estimating
the cost-effectiveness of vaccination against herpes zoster in England and
Wales. Vaccine 2009;27:145467.
21. Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja
M, Betts RF, Gershorn AA, Haanp ML, McKendrick MW, Nurmikko TJ,
Oaklander AL, Oxman MN, Pavan-Langston D, Petersen KL, Rowbotham MC,
Schmader KE, Stacey BR, Tyring ST, van Wijck AJM, Wallace MS, Wassilew
SW, Whitley RJ. Recommendations for the management of herpes zoster. Clin
Inf Dis 2007;44:S126.
22. Chen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment
for preventing postherpetic neuralgia. Cochrane Database Syst Rev
2014;2:CD006866.
23. Dworkin RH, Barbano RL, Tyring SK, Betts RF, McDermott MP, PennellaVaughan J, Bennett GJ, Berber E, Gnann JW, Irvine C, Kamp C, Kieburtz K,
Max MB, Schmader KE. A randomized, placebo-controlled trial of oxycodone
and of gabapentin for acute pain in herpes zoster. Pain 2009;142:20917.
24. Berry JD, Petersen KL. A single dose of gabapentin reduces acute pain and
allodynia in patients with herpes zoster. Neurology 2005;65:4447.
25. Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia
with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain
Symptom Manage 1997;13:32731.
26. Han Y, Zhang J, Chen N, He L, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2013;3:CD005582.
27. Ji G, Niu J, Shi Y, Hou L, Lu Y, Xiong L. The effectiveness of repetitive
paravertebral injections with local anesthetics and steroids for the prevention
of postherpetic neuralgia in patients with acute herpes zoster. Anesth Analg
2009;109:16515.
28. Greene K, Dworkin RH, Rowbotham MC. A snapshot and scorecard
for analgesic clinical trials for chronic pain: the RReACT database. Pain
2012;153:17947.
29. Munch T, Dufka FL, Greene K, Smith SM, Dworkin RH, Rowbotham
MC. RReACT goes global: perils and pitfalls of constructing a global openaccess database of registered analgesic clinical trials and trial results. Pain
2014;155:13137.
30. Dufka FL, Munch T, Dworkin RH, Rowbotham MC. Results availability for
analgesic device, complex regional pain syndrome, and post-stroke pain trials:
comparing the RReADS, RReACT, and RReMiT databases. Pain 2015;156:72
80.
31. Hempenstall K, Nurmikko TJ, Johnson RW, AHern RP, Rice AS. Analgesic
therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med
2005;2:e164.