Dr Carolina Venda Nova and Professor Joanna M. Zakrzewska Discuss Current Guidance on Trigeminal Neuralgia, Covering Diagnosis, Referral, and Shared Care
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Trigeminal neuralgia (TN) is a rare disorder in which a person feels brief attacks of severe pain in their face. It is usually first seen in either general practice or primary dental practice, occurs most frequently in people over 50 years of age, and is more prevalent in women than men.1
TN is a complex, long-term condition requiring a multidisciplinary approach. However, patients with symptoms of TN may be referred to a wide variety of specialists, and it can take several years before they see a specialist who follows current guidance.
TN is associated with serious pain and uncertainty, and can have a significant impact on a person's quality of life (QOL) and mood, especially if it is poorly managed.1–5 Studies have shown that patients with TN are at increased risk of anxiety, depression, and poor sleep;1 in turn, these factors increase their risk of suicide.2
Specialists rely on GPs for shared care.1,4 Therefore, it is important that primary care clinicians are aware of the condition and able to identify, manage, and refer patients with suspected TN appropriately. This article will describe the main features of TN, and explain how national guidelines can be used to ensure its optimal treatment by specialists and GPs on a shared-care basis.
Key Features and Diagnosis
TN is a unilateral, episodic condition that presents with severe attacks of facial pain usually lasting from a few seconds to a few minutes.4,6 These attacks can be spontaneous, but may also be triggered by light touches to the face, such as from eating, showering, or cold wind.4,5,7 The first attack of pain is often memorable, as it tends to be sudden and severe.4
It is the severity of the pain that prompts a person to see their GP, but—as the pain is often felt inside the mouth—they may instead see a dentist, who will inevitably look for a dental cause.4,8 Many patients will therefore undergo multiple, irreversible dental treatments before receiving a diagnosis, such as filling replacements, root canal therapy, or tooth extractions, none of which will resolve the issue.8
Initially, patients can experience anything from one to 50 attacks per day, many of which are of high intensity.1 Sometimes, the attacks will abate after a few weeks, but usually they continue until some form of medication is provided.1,4,5 Even if a period of remission occurs, the pain usually returns after several weeks or months, or occasionally years.1,4,9
A diagnosis of TN is made based on a detailed clinical history and clinical examination, but it can be more challenging to make in primary care—especially at first presentation—as the patient's pain history tends to be shorter.4,5 However, with time, patients usually go into remission,4,9 and this feature may aid a clinician in diagnosis.
Table 1 includes a few key questions to ask when considering a diagnosis of TN. It is best practice for any case of TN to be assessed and confirmed by a specialist.3–6,9
Table 1: Key Diagnostic Questions, Corresponding to the ICHD Diagnostic Criteria3–6,9
Question for patient
|Interpretation||ICHD diagnostic criteria|
|Do you remember exactly where you were or what you were doing the moment your facial pain started?||TN is usually associated with a memorable onset, and this is often reported by patients||Paroxysms of unilateral facial pain, precipitated by an innocuous stimulus|
|Did the pain begin suddenly?||Sudden pain is much more likely in TN than dental pain with gradual onset||Paroxysms of unilateral facial pain|
Are these attacks very severe?
Consider using a scale of 0–10
|First attacks are often very severe, and are the reason why patients are prompted to attend||Severe intensity|
|Has a dentist told you that that your episodic pain is not coming from the teeth?||This is important to check, as dental pain is very common||Not accounted for by any other diagnosis|
|Do any of these words reflect your pain?—shooting, stabbing, electric-shock like, burning, throbbing, aching||Patients will often choose these words without prompting, particularly shooting, stabbing, and 'like an electric shock'||Pain feels like an electric shock, and/or is shooting, stabbing, or sharp in quality|
Where do you feel the pain?
A diagram may be helpful
|Pain should usually be on one side of the face, most frequently in the maxilla and/or mandible, but rarely in the ophthalmic division of the trigeminal nerve||Unilateral face pain, distributed in one or more divisions of the trigeminal nerve|
|Do you feel the pain inside your mouth?||Many people will report pain intraorally, but not to the back of the tongue||Pain in the distribution of the trigeminal nerve, not radiating beyond|
|How long is each attack?||Individual attacks of TN should last for seconds, or at the most for 2 minutes, although a person can have a series of stabbing attacks over a longer period||Pain lasts for between a fraction of a second and 2 minutes|
|How many attacks of pain do you get per day?||Around 10 attacks are expected per day, but it could be more||Recurrent paroxysms of pain|
|What can trigger your pain?—e.g. brushing your teeth, eating, talking, washing your face||Light touch activities usually trigger the pain, as does eating||Pain is precipitated by innocuous stimuli within the affected area|
|ICHD=International Classification of Headache Disorders; TN=trigeminal neuralgia|
Secondary Causes and Differential DiagnosesWhen assessing suspected TN, it is crucial to determine whether there could be a secondary cause.3,5 Secondary causes include multiple sclerosis (MS) and brain tumours.1,3,4,10
TN can be the first presenting symptom of MS, and in some patients may be associated with sensory loss.10 A brain tumour, often a benign tumour such as a meningioma or a schwannoma, can also present with hearing loss and TN.11,12 A history of malignancy or the existence of other systemic symptoms, such as fever and weight loss, should prompt early referral to the appropriate specialist services, as should the following 'red flags':4
- sensory or motor deficits
- deafness or other ear problems
- optic neuritis
- bilateral TN pain
- presentation in a person aged under 30 years.
Guidelines on TN
International guidelines for the management of TN have been in existence since 2008, and an updated version of European guidance was published in 2019.3 These guidelines did not involve patients or other relevant stakeholders.
In 2021, a UK national guideline was published with the support of the Faculty of Dental Surgery of the Royal College of Surgeons of England. It was developed with input from major stakeholders in primary and secondary care, as well as from patients.4
At diagnosis, all patients should undergo imaging, preferably magnetic resonance imaging (MRI), to identify any underlying pathology or neurovascular compression.3,4 Ideally, this would be performed in a specialist centre.3,4 If MRI is not possible, computed tomography can be used instead to exclude an underlying pathology.3,4
As a wide range of treatments is available for TN, it is helpful to use patient-related outcome measures to guide management.4,14 The most important outcomes of TN management, as identified by patients and experts, include pain relief, pain interference, side effects of treatment, health-related QOL, satisfaction with treatment, and the ability to participate in social roles and activities.15 Patients should be encouraged to keep pain diaries, as they can help to gauge the effectiveness of treatment and inform medication adjustments and treatment escalation.4
Providing Information to Patients
When providing information to a patient about TN and its management, a clinician may wish to show them the national guideline, which includes a lay summary.4 It may also be useful to give patients separate written information about TN as well, covering both pharmacological and surgical options.4 The Brain and Spine Foundation, for example, offers a booklet covering all forms of facial pain, in particular TN—bit.ly/3CEpgos.16
Carbamazepine and oxcarbazepine
Carbamazepine is seen as the gold standard for initial pharmacological management, and is recommended for TN in NICE guidance on the management of neuropathic pain in nonspecialist care.3,17 However, the NICE guideline does not provide any guidance on prescribing.17 With carbamazepine, it is important to start with low doses10—the British National Formulary (BNF) recommends 100 mg one to two times per day, to be increased gradually according to response to a usual dose of 200 mg three to four times a day, up to a maximum of 1.6 g daily (if necessary).18
If carbamazepine cannot reach the therapeutic dose owing to intolerable side effects, if it fails to provide adequate pain relief, or if there is an absolute contraindication due to a drug interaction, oxcarbazepine can be prescribed, with a therapeutic range that is usually between 1200 and 1800 mg/day, separated into four doses.4 Oxcarbazepine is likely to be more effective than gabapentin or pregabalin. GPs can prescribe oxcarbazepine, although its use for TN is off licence; NICE guidance states that, if initial treatment with carbamazepine is unsuccessful, advice should be sought from a specialist.17
In the initial stages, carbamazepine can be considered a diagnostic drug, with many cases of TN responding quickly and effectively.3 However, side effects are common.3,4,18 Moreover, as carbamazepine is eliminated by the cytochrome P450 system, drug interactions with it are also common19—clinicians should be mindful of this, and be sure to check the BNF when prescribing.
When considering a carbamazepine or oxcarbazepine prescription, testing for the presence of the HLA-B*1502 allele is recommended in individuals of Han Chinese or Thai origin, as there is an increased risk of carbamazepine-induced Stevens–Johnson syndrome in this group.4,18,20,21
Even though the pain from TN can be very severe, use of opioids is not recommended as they are ineffective for the management of TN.3,4 Other drugs, such as amitriptyline, gabapentin, and pregabalin, are alternatives to carbamazepine, but are much less likely to be effective in the early stages and should only be initiated by specialists.4 Some patients may also need to take more than one anti-epileptic drug.4 In any case, if treatment has failed with carbamazepine monotherapy, patients should be referred to specialist centres for further guidance and treatment.4,17
Table 2 provides details of the main drugs indicated for TN.4,5,7,18,21–27 When prescribing, all healthcare professionals should consult the relevant BNF pages and summaries of product characteristics, particularly when considering off-licence use, and should provide patients and carers with written information and a dosage schedule.4 Specialists should also share information on medication schedules with a patient's GP, as they are often asked to continue drugs on prescription and arrange blood tests for monitoring.
There is some flexibility around dosage escalation should a flare-up occur suddenly.4 Adjuvant medications can be prescribed for acute attacks (see Relapses and Acute Therapy, below).4,5
Table 2: Drug Therapy for TN4,5,7,18,21–27
|Drug||Suggested initial dosage[A]||Suggested maintenance dosage[A]||Common side effects||Baseline investigations and monitoring (based on the authors' experience)|
|100 mg one to two times per day||200 mg three to four times per day, increased if necessary up to 1.6 g daily|
Refer to the BNFand the RCS guideline for more information on dose division for TN
|Dizziness, drowsiness, dry mouth, eosinophilia, fatigue, fluid imbalance, gastrointestinal discomfort, headache, hyponatraemia, leucopenia, movement disorders, nausea, oedema, skin reactions, thrombocytopaenia, vision disorders, vomiting, weight increase||Baseline tests: |
After 6 months, repeat FBC, U&E, and LFTs; warn of weight gain
Once stable, repeat U&E tests every 6 months and LFTs periodically
|300 mg two times per day with a 300 mg dose increase every 3 days||1200–1800 mg per day|
Refer to Lambru et al for more information on dose and dose division for TN
|Abdominal pain, agitation, alopecia, asthenia, ataxia, impaired concentration, constipation, depression, diarrhoea, dizziness, drowsiness, emotional lability, headache, hyponatraemia, nausea, nystagmus, skin reactions, vertigo, vision disorders, vomiting||As for carbamazepine, with more emphasis on U&Es|
|25 mg two times per day||25–400 mg per day |
Refer to Lambru et al and the RCS guideline for more information on dose division for TN
|Aggression, agitation, arthralgia, diarrhoea, dizziness, drowsiness, dry mouth, fatigue, headache, irritability, nausea, pain, rash, sleep disorders, tremor, vomiting||FBC, U&E, and LFTs annually|
|15 mg three times per day||15–90 mg three times per day|
Refer to Lambru et al, the RCS guideline, and the BNF for more information on dose and dose division for TN
|Confusion, constipation, depression, diarrhoea, dizziness, drowsiness, dry mouth, euphoric mood, hallucination, headache, hyperhidrosis, hypotension, nausea, paraesthesia, skin reactions, urinary disorders, vision disorders, vomiting||FBC, U&E, and LFTs annually|
|150 mg two times per day||150–600 mg per day|
Refer to Lambru et al, the RCS guideline, and the BNF for more information on dose division for TN
|Abdominal distension, abnormal appetite, asthenia, cervical spasm, impaired concentration, confusion, constipation, diarrhoea, dizziness, drowsiness, dry mouth, feeling abnormal, abnormal gait, gastrointestinal disorders, headache, increased risk of infection, joint disorders, memory loss, altered mood, movement disorders, muscle complaints, nausea, oedema, pain, abnormal sensation, sexual dysfunction, sleep disorders, speech impairment, vertigo, vision disorders, vomiting, weight changes||FBC, U&E, and LFTs annually|
Monitor for side effects
|300 mg three times per day||300–3600 mg per day|
Refer to Lambru et al, the RCS guideline, and the BNF for more information on dose division for TN
|Anxiety, abnormal appetite, arthralgia, asthenia, abnormal behaviour, confusion, constipation, cough, depression, diarrhoea, dizziness, drowsiness, dry mouth, dysarthria, dyspnoea, emotional lability, fever, flatulence, abnormal gait, gastrointestinal discomfort, headache, hypertension, increased risk of infection, insomnia, leucopenia, malaise, memory loss, movement disorders, muscle complaints, nausea, nystagmus, oedema, pain, abnormal reflexes, abnormal sensation, sexual dysfunction, skin reactions, abnormal thinking, tooth disorder, tremor, vasodilation, vertigo, visual impairment, vomiting||FBC, U&E, and LFTs annually|
|[A] The dosages suggested here reflect the need for gradual titration to minimise any adverse effects and achieve an optimal response. The final therapeutic dose and choice of drug(s) will vary from patient to patient. GPs should discuss and agree changes in dosages of medicines initiated in secondary care with specialists|
[B] The use of this drug for TN is currently off licence
[C] This is a Class C controlled substance
|TN=trigeminal neuralgia; BNF=British National Formulary; RCS=Royal College of Surgeons; FBC=full blood count; U&E=urea and electrolytes; LFT=liver function test|
Relapses and Acute TherapyThere is little available evidence on the natural history of TN, including on the length of remission and relapse periods. It is therefore difficult to provide a prognosis. Nevertheless, the national guideline recommends that patients slowly reduce and stop their medication when they are in a period of remission—that is, more than 4 weeks with no attacks.4 Some patients will be fearful of doing this, and may prefer to remain on a low dose of their medication.4
Relapses can start suddenly, and therefore require prompt action, often by a GP. Usually, it is best practice to restart the patient's last-used medication.4 If this is not effective, particularly for an acute exacerbation of pain, other drugs may need to be offered.3,4 Occasionally, it will be necessary to combine two drugs.3,4
Lidocaine can be helpful for relieving acute exacerbations, and can be bought over the counter or given via prescription as a spray or an ointment.4,5,28 Lidocaine is most useful for intraoral use if there is an intraoral trigger, and can be particularly helpful for patients who have difficulty eating and brushing their teeth.4
A dentist, oral surgeon, or TN specialist could also give a patient a local anaesthetic injection (lidocaine, with or without adrenaline) into the trigger-point area, which can be combined with a longer-acting agent such as bupivacaine.4 This would only provide a few hours of pain relief, but can be repeated daily until systemic drugs have reached their effective dose.4
In severe flare-ups, especially when associated with dehydration, patients should be admitted for treatment, ideally to a setting where a neurology team is available.3,4 These patients may require emergency surgery or intravenous medication.3,4
TN is one of the few chronic pain conditions in which surgical options can result in better outcomes than medical management.4,14 Surgery is a common choice for people with TN; in fact, a recent study conducted at a large teaching hospital found that over 50% of its patients with TN underwent surgery.14 However, surgery is irreversible, is associated with complications, and is not always fully effective—in the study, of those who underwent surgery, 55% of patients were free of pain and no longer taking medication, meaning that almost half of patients who underwent surgery were still affected by TN.14 Careful diagnosis is therefore imperative.
Patients should discuss surgical options early and while they are stable,3,4 so that they can think through their options in a rational way. It can be useful to give patients a decision aid such as the Ottawa Personal Decision Guide,29 which can help them in discussions with other patients, family members, and healthcare professionals.4,14
There is no strong evidence concerning the best time for surgery, but the following need to be considered:3–5
- use of multiple medications with diminishing efficacy
- poor tolerability of medication
- significant impact on mood and QOL.
Complications After Surgery
Cerebrospinal Fluid Leak
Patients may develop a cerebrospinal fluid leak 7–10 days after MVD, which can manifest itself as a leak through the wound, ear, or nose, and must be dealt with promptly by the neurosurgeon who carried out the procedure.4,14
The most significant long-term complication of surgery is sensory loss.4,5 This can vary in severity and distribution, and needs to be addressed and managed appropriately. The most severe form is anaesthesia dolorosa,3,5 a condition in which the patient feels complete numbness in the area innervated by the trigeminal nerve with an added continuous sharp pain. Some patients tolerate mild sensory changes, but in others they can lead to continued use of neuropathic drugs and a significant impact on mood and QOL.3,4
Patients who have lost their corneal reflex need to be given precise instructions on eye care and encouraged to wear glasses with side plates when going out in windy conditions.4 Hearing loss can be temporary, but in some will be permanent; unfortunately, little can be done about this.14
As surgical procedures are not curative, relapses are likely to occur. In some cases, these can be managed with drug therapy; in others, repeat surgery can be performed.1
It is now recognised that the pain, unpredictability, and reduced ability to carry out daily activities associated with TN are likely to have significant effects on a person's mental health, resulting in depression and anxiety.1,3,4 Therefore, patients will benefit from access to pain-management programmes,1,4 which can help them to improve their QOL.3,4,17
Specialist centres will often have clinical nurse specialists (CNSs), who are independent prescribers and can therefore arrange telephone consultations and advise patients on managing their medication.4 CNSs can also discuss the adjustment of drug dosages and prescriptions with GPs.4
Outside of healthcare services, people with TN may benefit from talking to other people with the condition.1,4 Trigeminal Neuralgia Association UK (TNA UK) is a charity offering help and support to people with TN, and offers a dedicated helpline run by volunteers.4,30 TNA UK also organises webinars, local support groups, and an annual conference. The charity is supported by a medical advisory board.
TN is a condition of unilateral, severe, episodic, facial pain that is provoked by light touch. Initially, it is usually well controlled with carbamazepine. National guidance provides details for both primary and secondary care practitioners on diagnosis, investigation, and management, which can be both pharmacological and surgical.
|Note: At the time of publication (July 2023), some of the drugs discussed in this article did not have UK marketing authorisation for the indications discussed. Prescribers should refer to the individual summaries of product characteristics for further information and recommendations regarding the use of pharmacological therapies. For off-licence use of medicines, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices for further information.|
|Implementation Actions for Clinical Pharmacists in General Practice|
Written by Shivangee Maurya, Clinical Services Pharmacist, Soar Beyond Ltd
The following implementation actions are designed to support clinical pharmacists in general practice with implementing guidance at a practice level.
As highlighted in the article, TN is a complex condition to diagnose and manage. The following implementation actions are designed to help clinical pharmacists in general practice support patients with TN:
The i2i Network has a suite of training and implementation resources, both bespoke and free, for clinical pharmacists in general practice, including e-learning, on-demand training delivered by experts covering a range of long-term conditions, and resources to help you put your learning into action. Become a free i2i Network member at: www.i2ipharmacists.co.uk.
TN=trigeminal neuralgia; MDT=multidisciplinary team; FBC=full blood count; U&E=urea and electrolytes; LFT=liver function test;QOL=quality of life
[A] Bendtsen L, Zakrzewska J, Abbott J et al. European Academy of Neurology guideline on trigeminal neuralgia. Eur J Neurol 2019; 26 (6): 831–849.