JOURNAL READING

Pharmaceutical Management of
Trigeminal Neuralgia in the Elderly
Ahmad Rizky Ferdina Kevin
2013 730 003
Preceptor:
dr. Djati Sulastono, Sp.S
 Introduction
Classical trigeminal neuralgia (CTN) is a severe neuropathic pain
in the distribution of one or more branches of the trigeminal
nerve, which occurs in recurrent episodes, causing deterioration
in quality of life, affecting everyday habits and inducing severe
disability. The annual overall incidence of TN ranges from
12.6/100,000 to 27/100,000 people per year, with an increase in
the incidence with advancing age. TN can be divided into
symptomatic TN (STN) and classical (idiopathic) TN (CTN).
 Introduction
The guidelines on pharmaceutical TN management published by
the American Academy of Neurology (AAN) and the European
Federation of Neurological Societies (EFNS) recommend
carbamazepine (CBZ; 200–1200 mg/day) or oxcarbazepine (OXC;
600–1800 mg/day) as first-line therapy.
 Objective
The aim of this review is to give an overview of the currently
available literature on the pharmceutical management of CTN
patients, with a focus on the elderly
 Materials and Methods
Inclusion and Exclusion Criteria
The studies included in this review were all double-blind, randomized,
controlled trials (RCTs) involving non-surgical treatment of CTN. The review
excluded articles on STN, articles not available in English and non-RCT study
designs.

Outcome Measures
Pain relief, defined as decreased frequency and decreased intensity of
painful paroxysms, was regarded as the primary outcome. Secondary
outcome measures were side effects
 Materials and Methods
Literature Searches
To identify eligible studies, Medline, Embase and Clinicaltrials. gov were
searched with the MeSH term ‘trigeminal neuralgia’. The search was
restricted to RCTs, clinical trials and English-language articles.

Data Collection and Analysis

The titles and abstracts of the articles were screened, and the two authors of
the review (MO and TF) decided which articles were eligible for inclusion.
Information on the numbers of participants, length of follow-up and
outcome measures was extracted from each article, using a data extraction
form.
 Materials and Methods
Assessment of Risks of Bias
The risks of bias in each trial were assessed by scoring the security of
randomization, allocation concealment, comparability of groups at
baseline, double blinding and handling of dropouts. In cases of
uncertainty, the authors of the relevant article were contacted
whenever possible.
Results
 Study Description

• The four studies investigating the effectiveness of CBZ, all published

before 1970, showed that CBZ reduced both the frequency and the
intensity of painful paroxysms in 76 %
• CBZ dosages ranged from 100 to 2400 mg/day. Side effects of drowsiness,
constipation, vertigo, nausea and vomiting, and a rash were described.
• Lamotrigine 200–400 mg as add-on therapy was shown to be an effective
and safe treatment, in comparison with CBZ alone, for management of TN
[14, 15] in 67 % of included patients with a mean age of 63 years (range
44–84).
 Study Description
Tizanidine 12–18 mg showed no greater effectiveness than CBZ or placebo in 22 patients,
with response rates of 56 % for tizanidine, 66 % for CBZ and 40 % for placebo

Baclofen was superior to placebo in reducing the number of painful paroxysms, with a 70
% response rate in 10 patients with a mean age of 64 years (range 36–77)

In a small group of 12 patients, tocainide was as effective as CBZ in reducing the frequency
and severity of pain attacks on a Visual Analogue Scale (VAS), with a response rate of 75 %

Pimozide was even more effective than CBZ in a single trial including 48 patients, with a
response rate of 100 % for pimozide versus 56 % for CBZ . The reported side effects were
physical and mental retardation, hand tremors and memory impairment in 83 % of the
pimozide group
 Study Description
Topical ophthalmic anaesthesia (proparacaine) was not effective in a single placebo-
controlled trial in 47 patients

Botulinum toxin (BTX) type A, administered subcutaneously, proved to be effective (with a

50 % response
rate, defined as a decrease in the VAS score of[50 %) in three placebo-controlled trials,
which included a total of 102 patients with a mean age of 57 years (range 30–88). The
reported side effects were transient, such as facial asymmetry, haematoma or oedema.

Sumatriptan, administered subcutaneously, was more effective than placebo (response

rate 83 %) in a single trial in a small group of 24 patients
 Discussion
According to the evidence in this review, the general first-line drug used in
medical management of TN is still CBZ. If there are unacceptable side effects,
which are mostly dose related and are more common in older patients, the
patient should be switched to OXC

Second-line treatment can be a combination of CBZ and lamotrigine or baclofen,

but the evidence for the use of either combination is still weak

BTX type A administered subcutaneously could be effective, but the evidence for
its use is weak as well. Local application of anaesthetics seems to be effective but
only for a few hours. The authors of the current review propose an algorithm of
evidence-based medical management of CTN
 Diagnostics in Trigeminal Neuralgia
• The diagnostic criteria suggested in the ICHD-3 [3] are at least three attacks
occurring in one or more divisions of the trigeminal nerve, with no
radiation beyond the trigeminal distribution.
• The pain has at least three of the following four characteristics:
1. Recurring in paroxysmal attacks lasting from a fraction of a second to 2
mint
2. Severe intensity
3. Electric shock-like, shooting, stabbing or sharp in quality
4. Precipitated by innocuous stimuli to the affected side of the face
Adverse Events and Side Effects of Antiepileptics

Side effects of CBZ include central nervous system (CNS) disturbances,

such as a lack of balance, dizziness and somnolence, skin rash, renal
dysfunction, leukopenia, elevation in liver transaminases,
hyponatraemia, thrombocytopenia, accommodation disorders, ataxia,
nausea and vomiting, cardiac arrhythmias and, in long-term use,
osteoporosis and folate deficiency
Interactions of Carbamazepine and Oxcarbazepine
CBZ is an inducer of cytochrome P450 (CYP) 3A4, which results in acceleration of the
metabolism of concurrently prescribed antiepileptics, tricyclic antidepressants,
antipsychotics, steroid oral contraceptives, glucocorticoids, oral anticoagulants,
cyclosporine, theophylline, chemotherapeutic agents and cardiovascular drugs

The chemical structure of OXC is similar to that of CBZ. Although the evidence of efficacy
is stronger for CBZ than for OXC, the latter may pose fewer safety concerns [9, 36]. CBZ is
contra-indicated in patients with atrioventricular (AV) block.
Special Recommendations for Antiepileptics in the Elderly

Dapat disarankan untuk menurunkan dosis inisial CBZ dan OXC pada
lansia ke 100 mg dan 150 mg, berturut-turut. Hitung jenis darah
lengkap, elektrolit dan fungsi hepar harus diukur berulang selama
terapi.
 Conclusions

For first-line treatment of TN, use of the algorithm presented in Fig. 2 is

advised. Prescribe antiepileptics in the elderly with extreme caution, and pay
attention to drug– drug interactions and side effects. In the literature, there
is a deficiency of research on CTN in the elderly. Further research should
focus on the efficacy and safety of the alternative non-surgical treatment
options. Older patients and patients with co-morbidities and concomitant
therapies should be included in the research population as well to allow
generalization of research conclusions to ‘real life’.