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 ElChami, MD; Christine Boutwell, MD; and
Hassim Ali, M.D.
Published in Neurology 2004;63:959-965
© 2004 American Academy of Neurology
February 25, 2004
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.
© 2004 American Academy of Neurology
February 25, 2004
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
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.
Class
III
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
Class
IV
© 2004 American Academy of Neurology
February 25, 2004
AAN Translation of evidence to level of
recommendation
Level
A
Level
B
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 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.
© 2004 American Academy of Neurology
February 25, 2004
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
Incidence
– Postherpetic neuralgia is relatively common, affecting
10–15 % of those with herpes zoster
– Incidence increases with age
© 2004 American Academy of Neurology
February 25, 2004
Clinical question
In patients with postherpetic neuralgia, which
treatments provide benefit in terms of decreased
pain and improved quality of life?
© 2004 American Academy of Neurology
February 25, 2004
Tricyclic antidepressants
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Evidence
Intervention
Results
ARR* / NNT**
Watson,
1992
I
• Amtriptyline vs.
maprotiline
• Double blind,
randomized,
crossover
Benefit found for
both treatment (AT >
MT) compared to
baseline
Watson,
1982
II
• Amitriptyline
• Double blind,
randomized, crossover
Significant benefit
for amitriptyline
ARR=62.5%
NNT=1.6
*AAR=absolute risk reduction
** NNT=number needed to treat
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Max, 1988 II
• Amitriptyline,
lorazepam, and
placebo
• Double blind,
randomized,
crossover
• 41 completed both
arms
• Amitriptyline has
improvement over
lorazepam and
placebo
KishoreKumar,
1990
• Despiramine vs.
benzotropine as
active placebo
• Double blind
randomized study
ARR=53%
NNT=1.9
II
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Watson,
1998
II
• Amitriptyline vs.
Nortriptyline
• Double blind,
randomized,
crossover
• 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
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Intervention
Evidence
Rowbotham, I
1998
© 2004 American Academy of Neurology
Results
ARR / NNT
• Gabapentin up
• Decrease of 2.1 on
to 3600 mg/d vs.
Gabapentin, 0.5
placebo
placebo.
• Double blind,
• Based on global
randomized
perception of change
66/94 improved on
gabapentin, 25/79 on
placebo
ARR=46.2%
NNT=2
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Max,
1988
(also
TCA)
II
• Amitriptyline,
lorazepam, and
placebo
• Double blind,
randomized,
crossover
• 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.
© 2004 American Academy of Neurology
February 25, 2004
Opioids
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Intervention
Evidence
Results
ARR / NNT
• 11 chose MS as
providing the most
relief
• 4 lidocaine
• 1 saline
• 3 reported no benefit
Rowbotham, I
1991
MS 0.3mg/kg vs.
lidocaine 5mg/kg
vs. placebo
Watson,
1998
• Oxycodone vs. • 38 completed study.
placebo
• Benefit of oxycodone,
approximately 50%
• Double blind,
decrease in visual
randomized, two
analog scale
way cross over
I
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Intervention
Evidence
Max, 1988
II
© 2004 American Academy of Neurology
Results
ARR / NNT
• Clonidine
• Benefit only for
0.2mg, codeine
clonidine over the rest.
120mg,
• Significant adverse
ibuprofen
effects rate.
800mg, placebo
• Double blind,
randomized
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.
© 2004 American Academy of Neurology
February 25, 2004
Topical and Intradermal
Agents
Anti-inflammatory agents
Capsaicin
Topical anesthetics
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence: Anti-inflammatory
agents
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Tajti, 1999
I
ASA in ointment
vs. lidocaine in
ointment
Benefit for both
compared to baseline
(20 vs. 2 for ASA and
15 vs. 3 for lidocaine)
McQuay,
1990
II
• Benzydamine
cream (a topical
NSAI) vs.
placebo
• Double blind
No benefit
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence Capsaicin
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Watson,1993
I
0.075% capsaicin
vs. placebo
• 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
Level of
Intervention
Evidence
Rowbotham,
1995
I
© 2004 American Academy of Neurology
Results
ARR / NNT
• Lidocaine base 5% • No significant
in gel vehicle,
relief for cranial
covered with
PHN,
occlusive dressing • Significant
vs. placebo
decrease in VAS
• Double blind,
by 14mm at 8
randomized, cross
hours for torso –
over
limb PHN
February 25, 2004
Class I and II Evidence Topical anesthetics
Author,
Year
Level of
Evidence
Rowbotham, I
1996
© 2004 American Academy of Neurology
Intervention
Results
ARR / NNT
• Lidocaine 5% in • Pain relief by
non-woven
12.3mm on visual
polyethylene
analog scale
patch
• 24 had from slight to
• Double blind
complete relief
randomized,
cross over
February 25, 2004
Class I and II EvidenceTopical anesthetics:
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Galer,
1999
I
• Lidocaine
patches vs.
placebo
• Enriched
population,
double blind,
randomized
• >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
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
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence NMDA
antagonist
Author,
Year
Level of
Evidence
Intervention
Nelson,
1997
I
dextromethorphan • 5 reported benefit for
vs. placebo
DM
• 3 for placebo
• (5 could not
complete study due
to sedation)
ARR 15.4%
NNT = 65
© 2004 American Academy of Neurology
Results
ARR / NNT
February 25, 2004
Class I and II Evidence NMDA
antagonist
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Eide,
1994
II
Ketamine
0.15mg/kg
vs.
MS 0.075 mg/kg
vs.
saline
• 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
© 2004 American Academy of Neurology
February 25, 2004
Class I and II Evidence: Other
Modalities
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Kotani,
2000
I
Intrathecal
methylprednisolone
plus lidocaine
vs.
intrathecal
lidocaine
vs.
no treatment
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
Level of
Evidence
Intervention
Kikuchi,
1999
II
• Intrathecal vs.
• At 24 weeks
epidural
substantial
methylprednisolone
benefit for
intrathecal
• 4 sessions at 1
week intervals
• Not for epidural
NNT = 1.4
© 2004 American Academy of Neurology
Results
ARR / NNT
February 25, 2004
Class I and II Evidence
Author,
Year
Level of
Evidence
Intervention
Results
ARR / NNT
Lewith,
1983
II
• Acupuncture vs.
mock
transcutaneous
electrical
stimulation
• Single blind,
randomized
• 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
• The minimal benefit reported for iontophoresis
of vincristine is negated by side effects.
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
• The following are effective and should be used in
the treatment of postherpetic neuralgia (Level A,
Class I and II):
– Tricyclic antidepressants (amitriptyline,
nortriptyline, desipramine and maprotiline)
– Gabapentin
– Pregabalin
– Opioids
– 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).
© 2004 American Academy of Neurology
February 25, 2004
Recommendations
The following treatments are not of benefit (Level
B, Class II):
– Acupuncture
– Benzydamine cream
– Dextromethorphan
– Indomethacin
– Epidural
methylprednisolone
© 2004 American Academy of Neurology
– Epidural morphine
sulfate
– Lontophoresis of
vincristine
– Lorazepam
– Vitamin E
– Zimelidine
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
© 2004 American Academy of Neurology
–Intralesional
triamcinolone
–Cryocautery
–Topical piroxicam
–Extract of Ganoderma
lucidum
–Dorsal root entry zone
lesions
–Stellate ganglion block
February 25, 2004
Recommendations
•
There is insufficient evidence at this time to
make any recommendations on the long-term
effects of these treatments.
© 2004 American Academy of Neurology
February 25, 2004
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.
© 2004 American Academy of Neurology
February 25, 2004
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
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.
© 2004 American Academy of Neurology
February 25, 2004
To view the entire guideline and additional AAN
guidelines visit:
www.aan.com/professionals/practice/index/cfm
Published in Neurology 2004;
© 2004 American Academy of Neurology
February 25, 2004