Treatment of trigeminal neuralgia

Definition

Trigeminal neuralgia (TN) is a unilateral painful disorder that is characterized by brief, electricshock-like pains, is abrupt in onset and termination, and is limited to the distribution of one or
more divisions of the trigeminal nerve. 

PHARMACOLOGIC THERAPY 

• initial treatment of most patients with classic TN (ie, TN that is idiopathic or caused by neurovascular compression).
• Surgery is reserved for patients who are refractory to medical therapy.
• Medical treatment of TN is based on the use of antiepileptic drugs.

A) First-line therapy

• should be carbamazepine (CBZ) (200–1200 mg/day) and oxcarbazepine (OXC) (600–1800 mg/day), according to current evidence-based treatment guidelines.
• Although the evidence for the efficacy of CBZ is stronger, OXC has a better safety profile. 

Carbamazepine 

• The usual starting dose is 100 to 200 mg BD.
• The dose can be increased gradually in increments of 200 mg daily as tolerated until sufficient pain relief is attained.
• The typical total maintenance dose is 600 to 800 mg daily, BD for tablets and extended release capsules, or QID when for oral suspension.
• The maximum suggested total dose is 1200 mg daily.
• Adverse effects include drowsiness, dizziness, nausea, and vomiting; slow titration may minimize these effects.
• Carbamazepine-induced leukopenia is not uncommon, but it is usually benign; aplastic anemia is a rare side effect. 
• The HLA-B*15:02 allele is a genetic susceptibility marker in Asians that is associated with an increased risk of developing Stevens-Johnson syndrome and/or toxic epidermal necrolysis. Screening for this allele in patients with Asian ancestry is recommended before to starting carbamazepine. If genetic testing results are positive for the presence of at least one copy of the HLA-B*15:02 allele, carbamazepine should be avoided.

Oxcarbazepine

• can be started at a total dose of 600 mg daily, given in two divided doses.
• The dose can be increased as tolerated in 300 mg increments every third day to a total dose of 1200 to 1800 mg daily.
• As with carbamazepine, we suggest testing for the HLA-B*15:02 allele in genetically at-risk populations (ie, those with Asian ancestry) before initiating treatment with oxcarbazepine. Oxcarbazepine, carbamazepine, and phenytoin should be avoided in patients carrying the HLA-B*15:02 allele unless the estimated benefits clearly outweigh the risks.

B) Second-line treatment

• based on little evidence and includes add-on therapy with lamotrigine (400 mg/day) or a switch to lamotrigine or baclofen (40–80 mg/day).

Baclofen

• The starting dose of baclofen is 15 mg daily given in three divided doses, with gradual titration to a maintenance dose of 50 to 60 mg per day.
• Sedation, dizziness, and dyspepsia can occur with treatment, and the drug should be discontinued slowly since seizures and hallucinations have been reported with upon withdrawal.

Lamotrigine

• In patients who are not taking other anticonvulsants, lamotrigine is typically started at 25 mg daily for the first two weeks, and then increased to 50 mg daily for weeks 3 and 4. The dose is then titrated to effect, increasing by 50 mg daily every one to two weeks. The suggested total dose of 400 mg daily is given in two divided doses.
• For patients taking an anticonvulsant drug that induces hepatic enzymes (eg, carbamazepine, phenytoin, or primidone), the initial dose of lamotrigine is 50 mg once daily, titrating upward as needed to 100 mg once daily at week 3, 200 mg once daily at week 5, 300 mg once daily at week 6, and 400 mg once daily at week 7.
• For patients taking valproate, the initial dose of lamotrigine is 12.5 to 25 mg every other day, with increases of 25 mg every two weeks as needed to a maximum of 400 mg per day.

C) Other antiepileptic drugs

• have been studied in small open-label studies.
• Treatment with phenytoin, gabapentin, pregabalin, and valproate is also been suggested to be beneficial.
• In an emergency, an intravenous infusion of fosphenytoin can be helpful, as well as local injections of lidocaine into trigger points (points from which pain arises).

OPIOIDS

• Although there are no controlled data regarding the efficacy of opioids in TN specifically, it has been used in patients with acute exacerbations of pain lasting for days to weeks.
• Opioids may help make the pain bearable while more effective long-term treatments take effect. Our experience with opioids suggests partial analgesia with central side effects (particularly sedation) when these drugs are used alone, as high doses of morphine, hydromorphone, or oxycodone are usually required.
• In combination with other neuropathic analgesics, opioids seem to be more effective at lower doses.

REFRACTORY PAIN 

• There is only limited evidence to support treatment alternatives for patients with TN who are refractory to first-line medical therapy.
• There are weak data to support botulinum toxin injections.
• Among oral drugs, some patients who fail carbamazepine monotherapy may benefit from combination therapy with gabapentin, lamotrigine, topiramate, baclofen, or tizanidine.
• Intravenous infusion of phenytoin, fosphenytoin, or lidocaine may provide analgesia while oral medications are titrated.
• Phenytoin and fosphenytoin are dosed at 250 to 1000 mg intravenously at no more than 50 mg/minute and lidocaine is given at 100 to 300 mg over one-half hour while monitoring pulse and blood pressure.
• Nevertheless, there are no randomized controlled trials comparing monotherapy with combination therapy for TN.

References:

1. http://www.iasp-pain.org/files/Content/ContentFolders/GlobalYearAgainstPain2/20132014OrofacialPain/FactSheets/Trigeminal_Neuralgia.pdf

2. Obermann, M. (2010). Treatment options in trigeminal neuralgia. Therapeutic advances in neurological disorders, 3(2), 107-115.

3. www.uptodate.com