Acta Neurol Scand 2005: 111: 229–232 DOI: 10.1111/j.1600-0404.2005.00300.
x Copyright
Blackwell Munksgaard 2005
Oxcarbazepine monotherapy in postherpetic
neuralgia unresponsive to carbamazepine
and gabapentin
Criscuolo S, Auletta C, Lippi S, Brogi F, Brogi A. Oxcarbazepine
monotherapy in postherpetic neuralgia unresponsive to carbamazepine
and gabapentin.
Acta Neurol Scand 2005: 111: 229–232.
Blackwell Munksgaard 2005.
Objectives – We present the results of a preliminary, open-label trial to
evaluate the efficacy and tolerability of oxcarbazepine in postherpetic
neuralgia (PHN) unresponsive to treatment with antiepileptic
drugs (carbamazepine and gabapentin) and local anesthetic blocks.
Materials and methods – Twenty-four patients were treated with
oxcarbazepine monotherapy for 8 weeks. Starting dose was
150 mg/day, subsequently increased by 150 mg/day every 2 days until
a maintenance dose of 900 mg/day. Pain was assessed using a visual
analog scale (VAS). Results – There was a significant decrease in the
mean VAS score following 8 weeks of treatment (D ¼ 5.33; paired
t-test: P < 0.0001) compared with baseline. Oxcarbazepine was
effective from the first week of treatment. There was a significant
reduction in allodynia, leading to improvements in patients’
functioning and quality of life. Oxcarbazepine was generally well
tolerated. Conclusion – Oxcarbazepine appears to be a promising
alternative monotherapeutic approach for patients affected by PHN.
Pain is a typical feature of acute herpes zoster and
in a proportion of patients persists beyond rash
healing. Currently, there is no clear consensus
about the point at which acute herpes zoster pain is
considered postherpetic neuralgia (PHN). Three
common definitions of PHN include pain persist-
ing 1 month after rash onset, pain persisting
3–6 months after rash onset, and pain persisting
at rash healing (1, 2). Symptoms of PHN are
mainly characterized by pain that can be steady
and burning, lancinating and itching, but this pain
is frequently associated with sensation abnormal-
ities such as allodynia, hyperalgesia, hyperesthesia
or hypoesthesia. In about 55% of cases, PHN is
located on thoracic dermatomes (3).
PHN affects approximately 10% of patients with
herpes zoster. The incidence of PHN is directly
related to age: PHN is relatively unusual in
patients <50 years old, yet it occurs in around
50% of patients ‡ 60 years old (4). As the general
population continues to increase in age, a further
increase in the incidence of PHN is likely.
ACTA NEUROLOGICA
SCANDINAVICA
S. Criscuolo1, C. Auletta2, S. Lippi1,
F. Brogi3, A. Brogi1
1
U.O.C. Terapia Antalgica e Terapia Postoperatoria,
Azienda Ospedaliera Senese Policlinico Le Scotte Siena;
2
Scuola di Specializzazione Anestesia e Rianimazione
Universit
degli Studi di Siena; 3U.O. Psichiatria
Universit
degli Studi di Siena, Siena, Italy
Key words: postherpetic neuralgia; neuropathic pain;
allodynia; oxcarbazepine; anticonvulsants
Amerigo Brogi, U.O.C. Terapia Antalgica e Terapia
Postoperatoria, Azienda Ospedaliera Senese, Policlinico
`Le Scotte´, Viale Bracci 2, 53100 Siena, Italy
Tel.: +39-0577585872
Fax: +39-0577586872
e-mail: am.brogi@ao-siena.toscana.it
Accepted for publication 5 April 2004
PHN is a feared complication of herpes zoster,
and often greatly reduces patients’ quality of life.
In particular, patients who suffer from allodynia
experience unpleasant sensory phenomenon such
as being unable to tolerate even the lightest contact
against the affected skin. As a consequence, they
may become isolated and suffer a significant degree
of depression and/or anxiety.
Treatment of PHN is still an unsolved problem,
partly due to the fact that the pathogenesis of this
condition is not completely understood. More
than half of patients fail to respond to pharma-
cologic treatments or experience intolerable side
effects. Tricyclic antidepressants (TCAs), antiepi-
leptic drugs (AEDs) such as carbamazepine,
topical capsaicin treatment, lidocaine patches,
and sympathetic nerve blocks have traditionally
been used to treat PHN. Recently the AED
gabapentin was found to be effective in patients
with PHN (5, 6).
Oxcarbazepine is an AED, which has been
used in several neuropathic pain conditions (e.g.
229
Criscuolo et al.

trigeminal neuralgia and painful diabetic neuro-
pathy) (7–11). The effectiveness of oxcarbazepine
in treating neuropathic pain is probably due to a
dual mechanism: the inhibition of sustained, high-
frequency, repetitive firing of voltage-gated sodium
channels combined with the inhibition of the high-
voltage P/Q and N-type calcium channels (12).
This results in a dose-dependent inhibition of
postsynaptic excitatory glutamatergic potentials
on striatal neurons.
We present the results of a preliminary, open-
label trial to evaluate the efficacy and tolerability of
oxcarbazepine monotherapy in PHN unresponsive
to treatment.
Materials and methods
Patients enrolled in this trial had to be diagnosed
with PHN and have presented with allodynia for
‡ 8 weeks, have failed previous treatment with
both carbamazepine and gabapentin at therapeutic
doses, presented with a history of severe pain, and
had a visual analog scale (VAS) score of ‡ 7 cm on
a 10-cm scale at baseline. Patients enrolled in the
study provided written informed consent. Patients’
demographic and clinical characteristics are listed
in Table 1. After discontinuation of other treat-
ments (treatment duration with carbamazepine
ranged from 4 months to 1 year; treatment dur-
ation with gabapentin ranged from 6 months to
2 years), oxcarbazepine was started at 150 mg/day
and gradually increased every 2 days by 150 mg/day
until the maintenance dose of 900 mg/day, which
was generally reached after 10 days of titration and
then maintained throughout the study. Target dose
of 900 mg/die was empirically chosen as the dose
with the best chance to optimize clinical efficacy
and tolerability.
Overall treatment duration was 8 weeks. Pain
was evaluated on a VAS at baseline, weeks 1 and 2
of treatment, and then every 2 weeks. To deter-
mine the extent of the allodynic area, each patient
underwent a complete neurological examination
that assessed sensitivity, allodynia, motor function,
tendon reflexes, and signs of both dorsal root
compression and lesions of the pyramidal bundle.
This examination was performed along with VAS
scores. Mechanical allodynia was measured using a
cotton bud and a pointed object, while thermal
allodynia was measured using an object heated to
either 20 or 40C to assess responses to hot and
cold, respectively.
A patient’s quality of life was investigated every
7 days by evaluating the mood of the patient,
eating and drinking, their ability to move about,
managing household chores and personal hygiene.
Improvements in patients’ functioning and quality
of life were assessed by spontaneous report to
determine the overall rating of patient satisfaction.
Adverse events (AE) were also collected.

Table 1 Demographic and clinical patient characteristics

Patient Sex Age (years) NPH location (dermatoms) Previous treatments

1 F 91 C4–C7 Gabapentin 900 mg/die, carbamazepine 600 mg/die

2 F 60 D1–D5 Gabapentin 900 mg/die, carbamazepine 600 mg/die
3 F 76 C5–D7 Gabapentin 900 mg/die, carbamazepine 600 mg/die
4 F 72 D11–L4 Gabapentin 900 mg/die, carbamazepine 600 mg/die
5 F 67 S1–S5 Gabapentin 1200 mg/die, carbamazepine 800 mg/die
6 F 89 L2–L4 Gabapentin 900 mg/die, carbamazepine 600 mg/die
7 F 70 L1–L4 Gabapentin 900 mg/die, carbamazepine 600 mg/die
8 F 77 C4–C7 Gabapentin 900 mg/die, carbamazepine 600 mg/die
9 F 54 Trigeminal dx Gabapentin 900 mg/die, carbamazepine 400 mg/die
10 F 71 D3–D10 Gabapentin 900 mg/die, carbamazepine 600 mg/die
11 F 40 Trigeminal dx Gabapentin 900 mg/die, carbamazepine 400 mg/die
12 F 69 D7–L3 Gabapentin 1200 mg/die, carbamazepine 800 mg/die
13 M 65 C3–C7 Gabapentin 1200 mg/die, carbamazepine 800 mg/die
14 M 70 D3–D10 Gabapentin 1200 mg/die, carbamazepine 800 mg/die
15 M 58 Trigeminal sx Gabapentin 900 mg/die, carbamazepine 400 mg/die
16 M 85 C3–C6 Gabapentin 400 mg/die, carbamazepine 600 mg/die
17 M 79 Trigeminal dx Gabapentin 1600 mg/die, carbamazepine 800 mg/die
18 M 83 D4–D11 Gabapentin 1600 mg/die, carbamazepine 800 mg/die
19 M 82 D2–D8 Gabapentin 1200 mg/die, carbamazepine 800 mg/die
20 M 69 L1–L5 Gabapentin 900 mg/die, carbamazepine 600 mg/die
21 M 75 Trigeminal sx Gabapentin 1200 mg/die, carbamazepine 800 mg/die
22 M 78 D1–D9 Gabapentin 900 mg/die, carbamazepine 600 mg/die
23 M 59 D4–D7 Gabapentin 1200 mg/die, carbamazepine 600 mg/die
24 M 65 L1–L4 Gabapentin 900 mg/die, carbamazepine 600 mg/die

230

Table 2 Patient responder rates (responder, VAS decrease >50%)
Responder, n (%) Evaluable patients, n
Week 1 0 24
Week 2 1 (4.8) 21
Week 3 7 (36.8) 19
Week 4 10 (52.6) 19
Week 6 16 (84.2) 19
Week 8 16 (84.2) 19
Results
Twenty-four patients (12 male, 12 female; mean
age 71
11.72 years) with PHN unresponsive to
carbamazepine and gabapentin at therapeutic
doses were enrolled in the study. Nineteen (79%)
patients completed the 8-week treatment period of
the trial. Five (21%) patients discontinued treat-
ment before the planned 8 weeks: three patients
due to lack of efficacy and two patients as a result
of AEs. All discontinuations occurred during the
titration period.
The mean VAS score at baseline was 8.2 cm (SD
1.2), decreasing to a mean of 6.4 cm (SD 1.2) after
1 week of treatment (Table 2). Following 8 weeks
of treatment, the mean VAS score had significantly
decreased from baseline (D ¼ 5.33; paired t-test:
P < 0.0001). Patient responder rates (VAS
decrease >50%) indicated a high response to
treatment (Table 2). After 8 weeks of treatment,
84% (16/19) of patients showed a VAS decrease
>50%. There was a clinically significant reduction
in allodynia. This led to an improvement in
patients’ functioning and quality of life as assessed
by the overall rating of patient satisfaction. Satis-
faction was rated as ‘very good’ by 50% of
patients, ‘good’ by 29% of patients and ‘not
satisfied’ by 13% of patients (i.e. the three patients
who discontinued treatment due to a lack of
efficacy).
Overall, oxcarbazepine was well tolerated, with
no AEs reported in 22 patients. The two patients
who discontinued because of AEs, reported mild to
moderate dizziness, nausea, and sedation.
Discussion
PHN is the most frequent and feared complication
of herpes zoster, especially in patients >50 years
old, and the incidence of PHN is expected to
increase with the increasing age of the general
population. Symptoms of PHN may be so severe
and disabling that patients’ quality of life can
dramatically deteriorate. Furthermore, in a signi-
ficant proportion of cases, available treatment
options are ineffective, unbearable due to side
Oxcarbazepine in postherpetic neuralgia
effects, or only partially effective. Among PHN
symptoms, allodynia is particularly unresponsive
VAS score (mean
SD)
to treatment.
6.44
1.25 Here we report the results of an open-label trial
5.19
1.36 of oxcarbazepine monotherapy in patients with
4.32
1.11 PHN refractory to carbamazepine and gabapentin.
3.68
1.06
3.21
0.98
Following administration of oxcarbazepine for
2.84
1.17 8 weeks, we observed a significant and clinically
relevant improvement in the signs and symptoms
of PHN, especially allodynia (13). Overall, 79%
(19/24) of patients completed the 8-week trial, and
84% (16/19) responded to oxcarbazepine therapy.
Patients’ quality of life consequently improved,
and they were able to return to their daily routine,
which had previously been given up as a result of
PHN. In these patients, oxcarbazepine improved
the symptoms of PHN from the first week while
patients were still in the titration phase (at doses
<900 mg/day). Oxcarbazepine had a statistically
significant effect on pain from the second week
onwards. The drug was well tolerated, with mild to
moderate side effects in only two patients.
The effectiveness of oxcarbazepine in treating
neuropathic pain is probably due to its dual mode
of action, which differentiates oxcarbazepine from
other AEDs such as carbamazepine. Oxcarbazepine
targets both peripheral and central mechanisms. It
slows the recovery rate of voltage-activated sodium
channels, which limits repetitive firing, modulates
high-threshold N- and P-type calcium channels,
and reduces glutamatergic transmission. In con-
trast, carbamazepine targets only peripheral mech-
anisms (14, 15).
Thus oxcarbazepine appears to be a promising,
alternative monotherapeutic approach for patients
affected by PHN. These preliminary findings
warrant further investigation with randomized,
controlled studies.
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