eMedicine Specialties > Neurology > Headache and Pain

Trigeminal Neuralgia: Treatment & Medication

Author: Manish K Singh, MD, Assistant Professor, Department of Neurology, Teaching Faculty for Pain Management and Neurology Residency Program, Hahnemann University Hospital, Drexel College of Medicine; Medical Director, Neurology and Pain Management, Jersey Institute of Neuroscience
Coauthor(s): Gordon H Campbell, MSN, Senior Nurse Practitioner, Department of Mental Health and Neuroscience, Portland Veterans Affairs Medical Center; Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health & Science University; Associate Director, Oregon Stroke Center; Siddharth Gautam, MBBS, Resident Physician, Jersey Neuroscience Institute
Contributor Information and Disclosures

Updated: Aug 21, 2009

Treatment

Medical Care

• Since most patients incur TN when older than 60 years, medical management is the logical initial therapy. Medical therapy often is sufficient and effective, allowing surgical consideration only if pharmacologic treatment fails. Medical therapy alone is adequate treatment for 75% of patients.
• Because this disorder may remit spontaneously after 6-12 months, patients may elect to discontinue their medication in the first year following the diagnosis. Most must restart medication in the future.
• Serum levels of carbamazepine (but not necessarily phenytoin) in ranges appropriate for epilepsy may be necessary, at least to control initial symptoms, although a much smaller maintenance dosage may be adequate thereafter.
• According to Dalessio, medications work by interrupting the temporal summation of afferent impulses that precipitate the attack.¹²
• Once a patient experiences breakthrough pain on a single agent, a second and even third additional medication may be required to restore relief.
• Carbamazepine is the drug of choice for TN. A 100-mg tablet may produce significant and complete relief within 2 hours, and for this reason it is a suitable agent for initial trial.
  • So predictable and powerful is the relief that if the patient does not respond at least partially to carbamazepine, reconsider the diagnosis of idiopathic TN.
  • If this dosage does not relieve the discomfort adequately, administer a higher dose.
• Gabapentin has demonstrated effectiveness, especially in patients with MS.
• In 1997, Sist et al reported 2 patients with TN responsive to gabapentin.¹³ One previously was unresponsive to carbamazepine.
• In 1998, Khan reported complete relief of secondary TN in 6 of 7 patients with MS receiving gabapentin doses from 900-2400 mg/d.¹⁴
  • The patients previously had not responded to a variety of drugs.
  • Once on gabapentin, 2 subjects were able to discontinue all other pain medications, and the remaining 5 could stop all but one other pain medication.
  • All patients maintained the response at 1 year of therapy with minimal adverse effects.
• In a similar, uncontrolled, small study of patients with MS, Solaro et al reported that 5 of 6 individuals found complete and sustained relief with gabapentin.¹⁵
• Lamotrigine, another new antiseizure medication, was reported by Lunardi et al to provide impressive and sustained relief of TN in one small, open-label, prospective study.¹⁶
  • All 5 patients with symptomatic TN associated with MS and 11 of 15 patients with idiopathic disease gained complete relief.
  • This was maintained during a follow-up period of 3-8 months.
  • Drug levels closely predicted pain relief, although the dosage required for adequate relief varied widely from 100-400 mg/d.
• To date, the efficacy of gabapentin and lamotrigine versus placebo or their efficacy in patients whose pain is refractory to carbamazepine has not been established. As stated by Carrazana and Schachter, of these 2 new agents, gabapentin has advantages, which include faster titration, no known drug interactions, and no known idiosyncratic skin reaction.¹⁷
• Phenytoin, although not approved by the FDA for idiopathic TN and believed to be less effective than carbamazepine, probably is effective for some patients with this disorder according to Loeser.¹⁸
  • It has the same mechanism of action as carbamazepine and poses a similar risk panel, except for the risk of aplastic anemia. Of those who fail to attain relief with carbamazepine alone, an additional 8-20% of patients may respond adequately if phenytoin is added to the treatment regimen.
  • According to one small study by Braham, phenytoin produced complete relief of pain in 30-40% of 43 patients and partial relief in an additional 30-40% at 300-600 mg/d.
  • Blom stated that doses of 300 mg/d were less effective, although doses of 400-600 mg caused more adverse effects.¹⁹
  • No correlation has been found between blood levels of phenytoin and therapeutic effect. Loeser recommends that the dose can be increased until relief is obtained or undesirable adverse effects appear (eg, dizziness, ataxia, diplopia, nystagmus, nausea).¹⁸
  • Raskin reports relief of intolerable pain with 250 mg of intravenous phenytoin over 5 minutes, allowing relief for hours to 3 days, sufficient for an adequate history and re-examination.²⁰
• Other anticonvulsant agents possibly useful in the treatment of this disorder include sodium valproate and clonazepam. According to Zakrzewska et al, their therapeutic efficacy has not been confirmed by formal studies.²¹
• The National Institute of Health (NIH) currently is sponsoring studies of topiramate.
• In 2006, He et al reported that the evidence from randomized controlled trials was insufficient to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia.²²
  • Baclofen may be effective in patients with TN. Tizanidine was investigated in a few trials but did not show significant benefit.
  • Commonly, baclofen is added to anticonvulsants when breakthrough symptoms occur.
  • In 1980, Fromm et al demonstrated baclofen to be useful in a small, uncontrolled study.⁸ Of the 14 patients with idiopathic TN resistant to carbamazepine, 10 found relief with 60-80 mg/d of baclofen.
  • The starting dosage is 10 mg/d, which can be increased, if needed, to 60-80 mg/d administered 3-4 times per day (it has a short half-life of 3-4 h).⁸
  • According to Parekh et al and Raskin, the dose of carbamazepine then may be reduced to 500 mg/d to maintain a putative synergistic effect.^23,20
  • In 1987, Fromm et al suggested that L-baclofen represents a significant improvement over racemic baclofen in the treatment of TN.²⁴
• The NIH also is investigating the use of dextromethorphan in doses much higher than those used in over-the-counter cough preparations.
• Tricyclic antidepressants (eg, amitriptyline, nortriptyline) have not been studied formally.
• Adjunct treatments such as mechanical, electrical, and thermal stimuli sometimes modify pain with fewer adverse effects than medication. Self-adhesive bandages may also be used.
• Depression is often seen in patients with TN. This underlying depression should be adequately treated.

Surgical Care

Over time, the drugs used for the treatment of TN often lose effectiveness as patients experience breakthrough pain. For patients in whom medical therapy has failed, surgery is a viable and effective option. According to Dalessio, 25-50% of patients eventually stop responding to drug therapy and require some form of alternative treatment.¹² The clinician then may consider referral to a surgeon for one of the procedures discussed below. Among patients who develop TN when younger than 60 years, surgery is the definitive treatment.

In 2008, Tatli et al reviewed surgical options, which mostly included microvascular decompression and radiofrequency thermorhizotomy. Their review suggests that each surgical technique for treatment of TN has merits and limitations. They also found that microvascular decompression provides the highest rate of long-term patient satisfaction with the lowest rate of pain recurrence.

Neurosurgery is generally more helpful in those patients with paroxysmal rather than constant pain and in patients whose pain follows the anatomic distribution of one or more trigeminal distributions rather than being spread diffusely. The various operations often fail after 1 or several years of initial relief. This requires a repeat procedure, often with improved but still incomplete results. Thus, many patients eventually restart pain medication after surgery.

Surgery appears to be less effective for TN secondary to MS.

Surgery exposes the patient to operative risks and the risk of permanent, residual facial numbness and dysesthesias. The primary complications of surgery include permanent anesthesia over the face or the troubling dysesthetic syndrome of anesthesia dolorosa—often disabling, occasionally is worse than the original TN, and often is untreatable.

Many operations have been offered to patients in recent decades. Local ablation of the peripheral nerve and wide sectioning of the sensory roots largely have been abandoned. In the past, alcohol injection was given to the affected nerve. Rhizotomy or tractotomy was recommended if pharmacological treatment was unsuccessful. 

Three operative strategies now prevail: percutaneous procedures, gamma knife surgery (GSK), and microvascular decompression (MVD). Ninety percent of patients are pain-free immediately or soon after any of the operations, although the relief is much more long-lasting with MVD. Pain-free intervals after percutaneous procedures (PRGR and PBM) last 1.5-2 years, 3-4 years after another (PRTG), and 15 years commonly after MVD.²⁵ Percutaneous surgeries make sense for older patients with medically unresponsive TN. Younger patients and those expected to do well under general anesthesia should first consider microvascular decompression–presently the most cost-effective surgery.

More recently, however, posterior fossa exploration has frequently revealed some structural cause for neuralgia (despite normal findings on CT, MRI, or arteriogram), such as an anomalous artery or vein impinging on the trigeminal nerve root. In such cases, simple decompression and separation of the anomalous vessel from the nerve root produces lasting relief of symptoms.

In elderly patients with limited life expectancy, radiofrequency rhizotomy is sometimes preferred, as it is easy to perform, has few complications, and provides symptomatic relief for a period of time.

The cost per quality adjusted pain-free year was $6,342, $8,174, and $8,269 for glycerol rhizotomy, microvascular decompression, and stereotactic radiosurgery, respectively, according to Pollack. Approximately 8000 patients with TN undergo surgery each year in the United States, at an estimated cost exceeding $100 million, as of 2005.

Many patients require pain medication even after surgery.

The primary complications of surgery include permanent anesthesia over the face or the troubling dysesthetic syndrome of anesthesia dolorosa. Anesthesia dolorosa can be disabling, occasionally is worse than the original TN, and often is untreatable. For this reason, procedures with the best long-term success and the least risk of a residual facial dysesthetic syndrome are the most promising.

• Percutaneous surgeries
  • Percutaneous procedures usually can be performed on an outpatient basis under local or brief general anesthesia at acceptable or minimal risk of morbidity. For these reasons, they commonly are performed in debilitated persons or those older than 65 years. Zakrzweska and Thomas described 3 types of procedures: percutaneous radiofrequency trigeminal gangliolysis (PRTG), percutaneous retrogasserian glycerol rhizotomy (PRGR), and percutaneous balloon microcompression (PBM).²⁶ Patients are left with minor, local, residual facial numbness after PRTG; may occasionally lose sensation after PRGR; and rarely do so after PBM. In each procedure, the surgeon introduces a trocar or needle lateral to the corner of the mouth and, under fluoroscopic guidance, into the ipsilateral foramen ovale. The ganglion is lysed at this location.
  • In PRTG, a radiofrequency heating tip sears the ganglion until the area of facial pain becomes numb. In PRGR, a spinal needle likewise penetrates the face, this time to the trigeminal cistern, at which point a cisternogram is obtained with water-soluble contrast material. After removing this material, the surgeon instills anhydrous glycerol, asking the patient to remain seated for an additional 2 hours to fully ablate the nerve.
  • With PBM, the operator inserts a balloon catheter through the foramen ovale into the region of the ganglion and inflates it for 1-10 minutes. PRTG has gained wide acceptance according to several investigators, because the patient is awake during the procedure, recovers quickly, and goes home the day of the procedure or the next day. According to Tan et al, the recurrence rate approaches 25% with PRTG, and occasionally patients suffer complications of jaw weakness and corneal anesthesia.
  • As related by Meglio and Cioni, some surgeons report excellent results with PBM, which are comparable to those with PRTG.²⁷ PRGR may be the favored procedure, as it includes only a minimal risk of disturbed facial sensitivity postoperatively. However, Cappiabianca et al and Taha and Tew, who favor the radiofrequency rhizotomy, argue that PRGR has the highest rate of pain recurrence.^28,29
• Gamma knife surgery
  • Gamma knife surgery (GKS) has become more widely available since 2000. It appears about as effective as the percutaneous procedures but takes weeks to months to bring relief and costs slightly more. It is effective in 80% of patients.
  • Kondziolka and Lunsford report that progress with this technique has been slow but has accelerated as surgeons have learned to target the nerve precisely with stereotactic MRI, have determined the proper radiation dose to quickly relieve pain without incurring facial sensory loss, and have ascertained the length of the nerve to be radiated.³⁰
  • In Kondziolka et al's study of 106 subjects, most patients already had no relief with either microvascular decompression or glycerol rhizotomy.³¹ At a median follow-up point of 18 months, 60% of patients were pain free, 17% were moderately improved, and 23% were minimally or not improved.
  • Kondziolka concludes that this technique is minimally invasive, is associated with a low risk (10%) of facial paresthesias or sensory loss, and offers a high rate (86%) of significant, initial pain relief.³¹
  • The pain recurrence rate is low for patients who initially attain complete relief. It is generally effective, even in patients in whom prior surgery or medication trials failed. Patients must wait 1 month for the pain to resolve.
  • Stereotactic GSK is less technically demanding, less operator-dependent, and less invasive than the percutaneous procedures. It is among the newest techniques for treating trigeminal neuralgia. It is the least invasive of the surgical procedures and has fewer complications.
  • In 1953, Leksell irradiated the trigeminal nerve in 2 patients with good initial success but did not publish this data until 1971.³² Progress really began when, in the 1990s, surgeons learned to target the nerve precisely with stereotactic MRI, determine the proper radiation dose to quickly relieve pain without incurring facial sensory loss, and ascertain the length of nerve to be radiated.
  • Henson compared GSK to PRGR in 188 patients and concluded that GSK improved pain more consistently and induced less residual facial paresthesia. Pollack reviewed a group of 121 individuals who underwent one or the other procedure and found the rates of complete pain relief similar, about 60% at 6 months and 54% at 24 months.
  • Sheehan reported in a study of 151 patients that 47% were pain-free after 1 year and 34% after 3 years. Nine percent suffered incurred new facial numbness after the procedure. In a similar but smaller study (N=49) of patients followed for a mean of 49 months, one third of whom had also failed either MVD or PRGR, GKS provided complete relief, even off medications, in 14 patients (32%) and partial but durable relief in 27 patients (61%) (McNatt). Others report rather disparate complete pain relief, from 42% (Jawahar) to 59 % (Drzymala) to 60% (Pollack) to 80% (Urgosik).
  • In these prospective but open and uncontrolled trials, complete pain relief predictably waned substantially by year 3-5, as with the percutaneous procedures.
  • Pain relief also arrives much more slowly, often coming only 3-12 weeks after the procedure, too long a wait perhaps for some individuals.
  • New facial numbness or paresthesias develop slowly over the first 12-15 months after GSK, reaching bothersome levels in 9-20% of patients.
• Microvascular decompression
  • Microvascular decompression commonly is performed in younger, healthier patients, especially those with pain isolated to the ophthalmic division or in all 3 divisions of the trigeminal nerve and in those with secondary TN. It is now the most common surgery performed for TN.
  • Surgeons perform the operation under general anesthesia, incising the skin behind the ear and performing a 3-cm craniectomy. After retracting the dura to expose the trigeminal nerve, they identify an arterial loop compressing the nerve as it enters the pons. They then pad the vascular structure with Teflon felt.
  • Patients spend 4-10 days in the hospital and another week convalescing at home. Thus, recovery is more prolonged than with percutaneous procedures.
  • Mortality for this more invasive procedure approaches 0.5%. Serious morbidity includes dizziness, temporary facial palsy, cerebrospinal fluid leaks, meningitis, cerebellar stroke, and hearing loss, which may occur in 1-5% of cases.
• Effectiveness of surgical procedures in TN has been studied.
  • Burcheil reports that 90% of patients are pain free after any of the operations mentioned above.¹¹ Those in whom the first percutaneous procedure fails may undergo a repeat procedure, which usually provides relief.
  • Sweet reports that pain-free intervals after PRGR and PBM procedures last 1.5-2 years, and they last 3-4 years after PRTG.²⁵ For the microvascular decompression procedure, 15 years of relief is typical.
  • Adverse effects of surgery include corneal anesthesia, facial numbness outside of the trigger zone, new facial pain, facial dysesthesias, and intracranial hemorrhage (rare). Anesthesia dolarosa (TN pain associated with dense hypesthesia) is usually a result of surgical treatment; this is difficult to treat.

Consultations

Neurosurgical consultation is needed when medical treatment does not effectively control episodes of breakthrough facial pain.

Diet

No dietary guidelines are known to improve the outcome in TN.

Activity

• Patients learn quickly to avoid activities that trigger episodes of trigeminal pain, such as rubbing the face. Men may choose to grow beards to avoid regular shaving.
• A patient information guide is available at Trigeminal Neuralgia Association, PO Box 340, Barnegat Light, NJ 08006. Phone: 609-361-0982; Fax: 609-361-0982.

Medication

Please see Medical Care section.

For most patients, those incurring TN after age 60 years, medical management is the logical initial therapy. Medical therapy often is sufficient and effective, allowing surgical consideration only if pharmacologic treatment fails. The overlap between the underlying pathophysiologic mechanisms of some epilepsy models and neuropathic pain models supports their use in neuropathic pain in general and in TN specifically. Their exact mechanisms of action remain unclear.

Antiepileptic drugs (AEDs) work well and have been known to do so since a study was completed with phenytoin (PHE) in 1942 (Bergouignan) and another with carbamazepine (CBZ) in 1962 (Blom, 1962). With 3 placebo-controlled crossover studies validating its efficacy in TN, providing relief by roughly 75% versus only 25% in the placebo arms (Killian, Nicol, Campbell), CBZ is the best studied drug for this disorder and the only one with FDA approval in the setting. Since the CBZ studies, however, newer second- and third-generation AEDs have expanded the choice of AED in TN, having demonstrated their efficacy in a variety of neuropathic pain syndromes, including TN, as well as in painful diabetic polyneuropathy and postherpetic neuralgia.

Because patients with TN will be using medications for years, perhaps decades, their cost is relevant. Generic CBZ is the cheapest; costs vary widely for the other agents, depending on the source, but approach a 4-fold increase for generic gabapentin (GBP), 8-fold for lamotrigine (LTG), 10-fold for topiramate (TPM), and 20-fold for oxcarbazepine (OCB) in moderate daily doses. To justify these hugely higher costs, providers can point to the promise of improved tolerability of the new agents, often a determining factor in a person with multiple sclerosis or with advanced age. Some drugs do not affect serious idiosyncratic hepatic and hematopoietic reactions, eliminating the burden and cost of routine laboratory monitoring. Some offer more linear pharmacokinetics and fewer drug-drug interactions, facilitating combination therapy. Some pose less long-term risk for osteoporosis. Further, some do not autoinduce their metabolism, simplifying dose titration and adjustment.

Most of the literature on medications for TN consists of case series, uncontrolled studies with less than a dozen subjects, or small randomized clinical trials, so the apparent efficacy of the drugs requires confirmation through well-designed, large, phase III trials. The controlled data published for LTG and BCF is promising but derives from studies with only 14 and 10 subjects, respectively.

No controlled data exist for the use of phenytoin, clonazepam, sodium valproate, oxcarbazepine, gabapentin, or mexiletine in TN; similarly, no controlled data exist for the common practice of adding a second drug when the first fails, except for the addition of LTG to CBZ. No head-to-head comparison studies of these agents exists, and only one surgery versus medication study has been published, limited to refractory TN, a small (N=15) trial. Only one Cochran review of medications for TN exists, and it looks only at CBZ, the traditional favorite. Confusion arises over outcome measures, as some researchers accept only complete relief of pain while others accept partial relief.

Serum levels of the anticonvulsants in ranges appropriate for epilepsy may be necessary, at least to control initial symptoms; a much smaller maintenance dosage may be adequate thereafter. Because this disorder may remit spontaneously after 6-12 months, patients may elect to discontinue medication, only to restart it when the pain recurs. Once a patient experiences breakthrough pain on a single agent, a second and even third additional medication may be required to restore relief, at which point, many seek a surgical solution. Resistance develops anywhere from 2 months to 10 years after treatment begins with the most studied and successful drug, CBZ.

Botulinum toxin was shown to be successful for at least 90 days in a single case report in a patient in whom CBZ and rhizolysis had previously failed.³³ Dextromethorphan failed in 2 patients with TN in a randomized, double-blind, crossover trial of patients with various facial neuralgias.³⁴ Tricyclic antidepressants (eg, amitriptyline, nortriptyline), as well as sodium valproate or pregabalin, have not been well studied. Anecdotal reports exist for success with clonazepam. Trials of newer N- methyl-D-aspartate receptor blockers have not been done. An NSAID, misoprostol, has shown modest efficacy in a small prospective open study in patients with MS.³⁵

Anticonvulsants

Reduce excitability of gasserian ganglion neurons, preventing anomalous discharges and related lancinating volleys of pain.

Carbamazepine (Tegretol)

Three small placebo-controlled studies (Killian, Nicol, Campbell) constitute the evidence for making CBZ the DOC for TN, with a number needed to of 1.8 (95% CI, 1.4-2.8). A 100-mg tab may produce significant and complete relief within 2 h, and, for this reason, a 100 mg bid prescription is suitable to start. If this initial dose fails, one may push the dose to 1200 mg daily, as the patient will tolerate, for initial relief; maintenance doses generally are lower, 100-800 mg daily bid. If using extended-release cap, begin with 200 mg qd and increase prn to maximum dose 1200 mg/d bid. So immediate, predictable, and powerful is the relief that if the patient does not respond at least partially to CBZ, one should reconsider the diagnosis of idiopathic TN. Note, however, that 15% of patients will not benefit from CBZ, forcing trials of other medications.

Gabapentin (Neurontin)

Small, uncontrolled studies have indicated possible effectiveness in patients whose pain has become refractory to carbamazepine; often is tolerated better than carbamazepine by elderly patients; no placebo-controlled studies have been published.

Lamotrigine (Lamictal)

This drug provided sustained relief in 2 small prospective studies. In one open label design by Lunardi et al (N=15), all 5 patients with symptomatic TN associated with MS and 10 of 15 patients with idiopathic disease gained complete relief when followed for 3-8 mo. Doses varied widely from 100-400 mg/d. In a double blind placebo controlled crossover study (N = 14), Zakrzewska and Thomas found 400 mg of LMT relieved the pain in 7 of 13 patients compared with only 1 of 14 on placebo.

Phenytoin (Dilantin)

Has similar mechanism of action as carbamazepine but is probably less effective; has several common adverse effects, which often are troublesome in older patients; drug levels do not always correlate with efficacy; may provide relief as an add-on drug when carbamazepine monotherapy wanes, as commonly happens after 1 or several years.

Topiramate (Topamax) - Experimental

In a pilot study of 3 patients enrolled in an NIH sponsored randomized, double-blind, placebo-controlled, 2-period crossover design, the authors could not confirm the benefits of topiramate (Gilron, 2001). It is a reasonable second-line agent. Zvartau-Hind et al reported success in an uncontrolled open label trial of 200-300 mg qd in 6 patients with MS, prescribed as monotherapy (in 5 of the 6 individuals) over a 6-mo interval. All 6 patients reported complete relief and appeared to tolerate the drug well. Solaro et al found 150-300 mg total daily doses relieved all TN pains in a case series of 4 patients, 2 with MS, 1 with idiopathic TN, and 1 with prior AVM resection, when followed for 6 mo. Carbamazepine and gabapentin had previously failed in all patients.

Oxcarbazepine (Trileptal)

Daily maintenance doses of oxcarbazepine 400-2400 mg/d were effective in several small uncontrolled studies (Farago, 1997). Three small multicenter double blind randomized trials found it as efficacious as carbamazepine in newly diagnosed or refractory TN and to be better tolerated (Beydown, 2002). Recommended starting dose is 300 mg bid.

This drug has not yet been approved by the FDA for trigeminal neuralgia (TN).

Antispasmodic agents

Several small, uncontrolled studies in the 1970s and 1980s, including those by Parekh et al and Fromm et al, demonstrated effectiveness of baclofen, particularly when added to an existing regimen of carbamazepine that is not providing adequate pain control. Once baclofen is added to an anticonvulsant, the dosage of the anticonvulsant often can be reduced.

Baclofen (Lioresal)

Only medication in this class with published data to support efficacy; may induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level.

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