What is the drug of choice for trigeminal neuralgia?

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What is the drug of choice for trigeminal neuralgia? is an uncommon disorder characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution. Typically, brief attacks are triggered by talking, chewing, teeth brushing, shaving, a light touch, or even a cool breeze. The pain is nearly always unilateral, and it may occur repeatedly throughout the day. The diagnosis is typically determined clinically, although imaging studies or referral for specialized testing may be necessary to rule out other diseases. Accurate and prompt diagnosis is important because the pain of trigeminal neuralgia can be severe.[Rx]

Treatment of Trigeminal Neuralgia

There are several effective ways to alleviate the pain, including a variety of medications.

  • Carbamazepine, an anticonvulsant drug, is the most common medication that doctors use to treat trigeminal neuralgia. In the early stages of the disease, carbamazepine controls pain for most people. When a patient shows no relief from this medication, a physician has cause to doubt whether trigeminal neuralgia is present. However, the effectiveness of carbamazepine decreases over time. Possible side effects include dizziness, double vision, drowsiness and nausea.
  • Baclofen is a muscle relaxant. Its effectiveness may increase when it is used with either carbamazepine or phenytoin. Possible side effects include confusion, depression and drowsiness.
  • Phenytoin, an anticonvulsant medication, was the first medication used to treat trigeminal neuralgia. Possible side effects include gum overgrowth, balance disturbances and drowsiness.
  • Oxcarbazepine, a newer medication, has been used more recently as the first line of treatment. It is structurally related to carbamazepine and may be preferred because it generally has fewer side effects. Possible side effects include dizziness and double vision.
  • Other medications include gabapentin, clonazepam, sodium valporate, lamotrigine and topiramate.
  • 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 [] in 67 % of included patients with a mean age of 63 years (range 44–84). The reported side effects were a headache, dizziness and a skin rash.
  • 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. Drugs with local administration have been studied in single trials as well.
  • Topical ophthalmic anesthesia (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, hematoma or edema.
  • Sumatriptan – administered subcutaneously, was more effective than placebo (response rate 83 %) in a single trial in a small group of 24 patients []. Lidocaine 8 % applied on the mucosa or administered via the intranasal route was effective in 85 % of 49 patients in two placebo-controlled trials, but the effect diminished after approximately 3 h [].
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Type Drug Brand Name Manufacturer
Anti-epileptic Carbamazepine Carbatrol, Equetro, Tegretol, Tegretol XR Shire Pharmaceuticals, Validus Pharmaceuticals, Novartis Pharmaceuticals
Anti-epileptic Felbamate Felbatol Meda Pharmaceuticals
Anti-epileptic Gabapentin Neurontin Pfizer
Anti-epileptic Lamotrigine Lamictal GlaxoSmithKline
Anti-epileptic Levetiracetam Keppra UCB
Anti-epileptic Oxcarbazepine Trileptal Novartis Pharmaceuticals
Anti-epileptic Pregabalin Lyrica Pfizer
Anti-epileptic Tiagabine Gabitril Cephalon
Anti-epileptic Topiramate Topamax Ortho-McNeil-Janssen Pharmaceuticals
Anti-epileptic Valproate Depakote, Depakote ER, Depakene, Depacon, Valproate, Valrelease Abbott Laboratories
Anti-epileptic Zonisamide Zonegran Dainippon
Anti-spasticity Baclofen Lioresal, Lioresal Intrathecal, Gablofen Various Drug Companies
Anti-epileptic Phenytoin Dilantin, Phenytek
Anti-epileptic Clonazepam Klonopin, Rivatril
Anti-depressant Amitriptyline Elavil
Anti-depressant Protriptyline Vivactil
Anti-depressant Nortriptyline Pamelor
Anti-depressant Fluoxetine Prozac, Seronil, Fontex
Anti-depressant Trazodone Desyrel
Opioids Morphine
Opioids Codeine
Opioids Fentanyl
Opioids Hydrocodone
Opioids Hydromorphone
Dermatologic Lidocaine
Dermatologic Lidoderm patch
Dermatologic Lidocaine cream
Dermatologic Capsaicin
Antianxiety SSRIs Paxil, Celexa
Antianxiety Benzodiazepines Ativan, Valium, Xanax, Klonopin
Analgesic Ultram Tramadol
Analgesic Ketamine
SNRIS Venlafaxine Effexor – serotonin/norepinephrine reuptake inhibitors
SNRIS Duloxetine Cymbalta – serotonin and noradrenaline reuptake inhibitor

Surgery of Trigeminal Neuralgia

If medications have proven ineffective in treating trigeminal neuralgia, there are several surgical procedures that may help control the pain. Surgical treatment is divided into two categories: percutaneous (through the skin) and open. In general, percutaneous approaches are preferred in older or medically frail patients, in patients with multiple sclerosis, or in individuals who have failed to attain pain relief from the open approach. The open approach is recommended for younger and healthier patients. All of the procedures have varying success rates and some side effects, such as recurrence of pain and facial numbness.

  • Microvascular decompression – Involves microsurgical exposure of the trigeminal nerve root, identification of a blood vessel that may be compressing the nerve and gentle movement of the blood vessel away from the point of compression. Decompression may reduce sensitivity and allow the trigeminal nerve to recover and return to a more normal, pain-free condition. While this generally is the most effective surgery, it also is the most invasive, because it requires opening the skull through a craniotomy. There is a small risk of decreased hearing, facial weakness, facial numbness, double vision and stroke or death. The risk of facial numbness, however, is less likely with procedures that involve damaging the trigeminal nerve.
  • Percutaneous stereotactic rhizotomy – Treats trigeminal neuralgia through the use of electrocoagulation (heat). It can relieve nerve pain by destroying the part of the nerve that causes pain and suppressing the pain signal to the brain. The surgeon passes a hollow needle through the cheek into the trigeminal nerve. A heating current, which is passed through an electrode, destroys some of the nerve fibers.
  • Percutaneous glycerol rhizotomy – Utilizes glycerol injected through a needle into the area where the nerve divides into three main branches. The goal is to damage the nerve selectively in order to interfere with the transmission of the pain signals to the brain.
  • Percutaneous balloon compression – Utilizes a needle that is passed through the cheek to the trigeminal nerve. The neurosurgeon places a balloon in the trigeminal nerve through a catheter. The balloon is inflated where fibers produce pain. The balloon compresses the nerve, injuring the pain-causing fibers. After several minutes, the balloon and catheter are removed.

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  • Stereotactic radiosurgery – (through such procedures as Gamma Knife, Cyberknife, LINAC) delivers a single highly concentrated dose of ionizing radiation to a small, precise target at the trigeminal nerve root. This treatment is noninvasive and avoids many of the risks and complications of open surgery and other treatments. Over a period of time and as a result of radiation exposure, the slow formation of a lesion in the nerve interrupts transmission of pain signals to the brain.
  • Motor cortex stimulation – is another option, but often is considered a last resort because it can be very difficult to predict which patients may benefit. While about half of patients experience pain relief, it tends to be short-term. This is an open procedure with all of the risks of microvascular decompression, but without the high success rates. The benefits of surgery should always be weighed carefully against its risks. Although a large percentage of trigeminal neuralgia patients report pain relief after surgery, there is no guarantee that surgery will help every individual.
  • Percutaneous procedures on the Gasserian ganglion – gamma knife and microvascular decompression are recommended, efficacy-proven surgical treatment options for medical refractory TN. Surgery for TN is either destructive (ablative), where the trigeminal nerve sensory function is intentionally destroyed, or non-destructive, where the trigeminal nerve is decompressed preserving its normal function.
  • Gasserian ganglion percutaneous techniques –  are all destructive and include radiofrequency thermocoagulation (RFT), balloon compression (BC) and percutaneous glycerol rhizolysis (PGR). Ninety percent of patients report pain relief following these procedures. After 1 year, 68–85% of patients are still pain-free, after 3 years this is reduced to 54–64% and after 5 years only 50% of patients are still pain-free following RFT. The most common side effects are a sensory loss (50%) which extremely decreases the quality of life [], dysesthesias (6%), anesthesia Dolorosa (4%), corneal numbness with the risk of keratitis (4%). Gasserian ganglion therapies require short-acting anesthetics, are primarily overnight minor procedures with extremely low mortality [].
  • In gamma knife surgery – a focused beam of radiation is aimed at the trigeminal root in the posterior fossa. One year after gamma knife surgery, 69% of patients are pain-free without additional medication. At 3 years, 52% are still pain-free. The development of pain relief can be delayed (mean 1 month). Side effects are sensory complications in 6% that may develop with a delay of up to 6 months, facial numbness in 9–37% which improves over time and paresthesias in 6–13% []. Quality of life improves by 88% []. The main disadvantage of gamma knife surgery is the treatment expense that limits widespread usage making it a reserve treatment option for patients that cannot undergo open surgery or have blood coagulation problems (e.g. are receiving warfarin).
  • Microvascular decompression – achieves the most sustained pain relief with 90% of patients reporting initial pain relief and over 80% still pain-free after 1 year, with 75% after 3 years and 73% after 5 years remaining pain-free. It is, however, a major surgical procedure that entails craniotomy to reach the trigeminal nerve in the posterior fossa. The average mortality rate ranges from 0.2% to 0.5%, and up to 4% of patients suffer from major problems such as cerebrospinal fluid (CSF) leakage, infarcts or hematomas. The most common complications are aseptic meningitis (11%), sensory loss (7%) and hearing loss (10%) as long-term complications [].
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Alternative Treatment of Trigeminal Neuralgia

  • Ignition hypothesis – According to the ignition hypothesis, based on recent advances in the understanding of the electrical behavior of injured sensory neurons and on findings from histopathologic observations obtained from patients undergoing MVD, injury of trigeminal afferent neurons in the trigeminal root or ganglion makes these axons and axotomized somata hyperexcitable, giving rise to pain paroxysms as a result of synchronized afterdischarge activity.
  • Transcranial magnetic stimulation – Repetitive transcranial magnetic stimulation (rTMS) is an emerging technology that introduces the possibility of assessing whether patients with trigeminal neuropathic pain will respond to direct epidural cortical stimulation by first measuring their response to a trial of non-invasive cortical stimulation. In a study of 24 TN patients given rTMS to the motor cortex at 20 Hz daily for 5 days, pain ratings decreased by approximately 45% for 2 weeks []. In a different study of 12 patients with chronic intractable TN who had failed surgical treatment, 58% experienced a greater than 30% reduction in pain after receiving repetitive TMS [].
  • Alternative Medicine – This section contains a wide variety of so-called “alternative” treatments. Some are medical treatments that are generally used for other purposes, but which have anecdotally been used to try to treat facial neuralgia pain. Most of this anecdotal information has been gathered from feedback with facial neuralgia sufferers. They may or may not be effective; the important point is that someone has tried them. Some of the treatments in this category are what is often known as “pseudo-scientific”. That is, there seems to be no rigorous scientific basis for them.
  • Anesthetics – There is some anecdotal evidence for the use of various anesthetic substances for treating acute attacks of facial neuralgias. Some of these substances should only be used under professional supervision. In general, any pain relief is likely to be short-lived. In addition, these treatments are probably more effective for cases of atypical TN than for classical TN.
  • Capsaicin – Has been anecdotally used, especially for atypical forms of TN and atypical facial pain. This is becoming more of a mainstream treatment and possibly should be included as a standard drug treatment instead of an alternative treatment.
  • Lidocaine cream/patch –  Again, relatively harmless if used properly.
  • Lidocaine nose sprays
  • Therapeutics – This group includes a variety of substances that have been suggested for facial neuralgia pain. Some of the substances may raise controversy, but an attempt has been made to avoid listing any substances that are directly harmful or poisonous.
  • Herbal remedies – various herbal regimes have been suggested for TN.
  • Homeopathy – a controversial treatment, but has been used by some.
  • Vitamin B12 –In her B12 study “DO TN patients have a B12 deficiency and Is there a role of Vitamin B12 in TN Management:  Irene Wood found those who used B12 supplements were able to lessen their pain, and some were also able to achieve “no pain no medication. Many in our Association are now using B12 supplements to help manage their pain. The hypothesis is repairing of the myelin (re-myelination). Low Vitamin B12 Syndrome in Trigeminal Neuralgia.
  • Musculoskeletal – These treatments treat the muscles rather than dealing with the nerve directly. At the very least, this relaxation can make it easier to deal with the pain. It is also possible that some cases of facial neuralgias are made worse by muscular strain, in which case these treatments could provide direct help. For classical TN, these treatments are likely to have little effect; however, they may well help those with more atypical symptoms.
  • ChiropracticAtlas Orthogonal Chiropractic focuses on aligning the C1, C2. Has helped others in achieving pain-free.
  • Myotherapy/myofascial release therapy
  • Cranial Osteopathy/Craniosacral therapy
  • Acupuncture – These treatments treat the nervous system directly (at least in theory). For lack of a better term, they can be classified under the term acupuncture-like. All have been reported to be used for facial neuralgia pain; as with all alternative treatments, the results have been inconclusive. It is used relatively commonly; however, reliable success rates are almost impossible to calculate.
  • Laser treatment – new, experimental treatment. The mechanism may be somewhat similar to acupuncture
  • Moxa therapy – similar to normal acupuncture.
  • TENS – electrical treatment; effects may be similar to acupuncture.
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Psychological

  • Hypnosis – This has been suggested for atypical as well as classical forms of TN. Only anecdotal evidence for it seems to exist so far. However, even some reputable textbooks do mention it as a reputable treatment.

References

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