Trigeminal Neuralgia
Ronald Brisman, M.D.

Medicines Trigeminal Neuralgia

 Medicines for Trigeminal neuralgia

 What medicines are helpful for patients with trigeminal neuralgia?

Most of the medicines that are helpful for treating trigeminal neuralgia are anti-seizure medicines even though trigeminal neuralgia is not a seizure and is not epilepsy. The most effective are carbamazepine (Tegretol) and oxcarbazepine (Trileptal). They are so effective that if a patient has never responded to them, the diagnosis of trigeminal neuralgia should be doubted. Also helpful are gabapentin (Neurontin), pregabalin (Lyrica) and lamotrigine (Lamictal), levetiracetam (Keppra), clonazepam (Klonopin), topiramate (Topamax) and phenytoin (Dilantin). Baclofen (Lioresal) is a muscle relaxer and not an anti-seizure medicine and it has also sometimes been helpful for patients with trigeminal neuralgia.


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 Carbamazepine for treatment of trigeminal neuralgia.

Carbamazepine (Tegretol) (carbamazepine is the generic name and Tegretol is the trade name) is often highly effective for trigeminal neuralgia. There are many possible side effects from Tegretol. Some of the more common ones are sleepiness, forgetfulness, confusion, drowsiness, dizziness, nausea and skin rash. Tegretol can cause more serious problems such as bone marrow suppression, which can cause anemia (not enough red blood cells) or a decrease in the number of white blood cells. A low white blood cell count can predispose to infection. Rarely, these problems are life threatening, and blood counts have to be monitored. Tegretol can also harm many other parts of the body, so patients who take this medicine must be under careful medical supervision. Tegretol also interacts with many medicines. Patients must advise their doctor about all their medicines. Elderly patients and those with multiple sclerosis are more likely to be bothered by Tegretol and most of the other anti-seizure medicines that are given to treat the pain of trigeminal neuralgia. Unpleasant side effects from carbamazepine (Tegretol) or oxcarbazepine (Trileptal), especially fatigue and impaired memory, occur more frequently as the dose is increased, and women are more likely than men to suffer from these and at lower doses (J Headache Pain. 2015;16:563. doi: 10.1186/s10194-015-0563-z. Epub 2015 Sep 3).

Blood levels of carbamazepine can be determined and are sometimes helpful in establishing the best dose. Some very severe skin disorders may occur rarely with the use of carbamazepine. Patients of Asian ancestry are more likely to have this complication. A blood test may be recommended for those of Asian ancestry (to show the HLA-B*1502 allele), because its presence increases the risk of these patients developing these skin disorders and, if positive, they should probably not take carbamazepine.

Hypertension is a rare side-effect of carbamazepine (Tegretol) [Kharb P, Mittal N, Gupta MC. Carbamazepine-induced hypertension: A rare case. J Pharmacol Pharmacother [serial online] 2015 [cited 2016 Feb 1]; 6:216-8. Available from: http://www.jpharmacol.com/text.asp?2015/6/4/216/171879.

In addition, in some patients who are taking antihypertensive medicines, carbamazepine may worsen hypertension by inducing the breakdown and decreasing the effectiveness of these antihypertensive medicines. Patients who have frequent severe pains from trigeminal neuralgia may develop high blood pressure just in reaction to the pain. Once the pain is relieved, the blood pressure may return to normal.

The dose of carbamazepine for trigeminal neuralgia is usually 200 mg three or four times a day. A liquid form exists for those who have trouble swallowing a pill; it contains 100 mg of carbamazepine in each 5 ml (teaspoon). A long-acting form of carbamazepine exists and is given two to three times a day.


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 Oxcarbazepine (Trileptal) for trigeminal neuralgia

Oxcarbazepine (Trileptal) is similar to carbamazepine (Tegretol) and also works very well for trigeminal neuralgia. Trileptal has fewer side effects. Serious side-effects are uncommon, but have occurred. Oxcarbazepine is less likely than Tegretol to cause bone marrow suppression or liver toxicity and has fewer interactions with other medicines. About 25 to 30 percent of patients who have a rash from carbamazepine will have a rash when they take oxcarbazepine. It may cause dizziness, drowsiness, headaches, fatigue, impaired balance, nausea or vomiting. It is more likely than Tegretol to cause low levels of sodium in the blood especially at higher doses or when taken with excessive amounts of liquids or other medicines, such as diuretics, which also can lower the sodium. Mild lowering of sodium is often without symptoms, but severe lowering of sodium can cause lethargy, seizures or loss of consciousness, and blood tests are needed to determine the level of sodium in the blood. Oxcarbazepine is taken two or three times a day and the dose is 50 percent more in milligrams than carbamazepine. (300 mg of oxcarbazepine is roughly equivalent to 200 mg of carbamazepine.) Blood levels of oxcarbazepine can be obtained and are sometimes helpful in determining the best dose. Many healthy adults can tolerate up to 1800 mg a day of Trileptal, but smaller doses should be used for those over 65 years of age or those with multiple sclerosis.

Oxtellar XR (oxcarbazepine extended release tablet) is a new, long-acting formulation of oxcarbazepine (Trileptal) -- an anti-seizure medicine that is sometimes used to treat trigeminal neuralgia. Possible good features of Oxtellar XR relate to patient convenience because it may be given only once a day. Regular oxcarbazepine (Trileptal) is usually given two or three times a day. Because Oxtellar XR provides a lower peak blood level, it may have fewer side effects than regular oxcarbazepine. However, at a similar total daily dose, Oxtellar XR (which provides less bioavailability of its active ingredient than regular oxcarbazepine) may also be less effective in relieving the pain of trigeminal neuralgia.

Side effects from Oxtellar XR are similar to those of oxcarbazepine and may include low sodium levels in the blood (hyponatremia), skin rash, nausea, dizziness, somnolence and psychiatric symptoms.

Oxtellar XR should not be given to someone who is allergic to oxcarbazepine. Oxtellar comes in 150 mg, 300 mg and 600 mg tablets. It should be taken on an empty stomach, either one hour before or 2 hours after eating, to prevent a more rapid release of its active ingredient. It is relatively expensive.


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 Gabapentin (Neurontin) and Pregabalin (Lyrica) for trigeminal neuralgia

Gabapentin (Neurontin) is less effective in relieving the pain of trigeminal neuralgia and is often given in addition to carbamazepine or oxcarbazepine when pain persists. Gabapentin, especially at lower doses, has fewer side effects than the other medicines, and blood tests do not need to be monitored frequently. Starting doses are between 100 to 300 mg, two or three times a day. This is gradually increased until pain relief or toxicity develops. Weight gain, ankle swelling and dry mouth are not uncommon. Much higher doses, up to 3600 mg a day, are sometimes needed. At high doses, some patients develop lethargy, unsteadiness, confusion or trembling.

Warning about gabapentin (Neurontin), oxcarbazepine (Trileptal) and trigeminal neuralgia: Neurontin, oxcarbazepine and drinking a lot of water (or other liquids) can cause low blood sodium (hyponatremia), which if excessive, can make you very sick.

The manufacturer of Neurontin has added a warning to the use of Neurontin saying that Neurontin capsules should be swallowed whole with plenty of water (http://labeling.pfizer.com/ShowLabeling.aspx?id=630). This may be related to a recent report of a mild case of irritation of the esophagus associated with a capsule of Neurontin whose identifying labelling was stuck to the inside of the esophagus. This was detected at endoscopic examination of the esophagus. Neurontin may also cause a dry mouth (reported in 5 of 336 patients taking Neurontin as opposed to one of 227 taking placebo) and this may also prompt some patients to drink a lot of water.

Patients with trigeminal neuralgia who take Neurontin often take oxcarbazepine, which is sometimes associated with hyponatremia (low sodium in the blood) usually because oxcarbazepine may decrease the patient’s ability to eliminate water. Carbamazepine (Tegretol) can have a similar effect. Diuretics also promote hyponatremia. Some other medicines (including many antidepressants and narcotics) may also cause a dry mouth and this could encourage patients to consume too many liquids.

Patients who take oxcarbazepine or carbamazepine should be careful not to consume excessive amounts of water. Those who take Neurontin (and oxcarbazepine) and want to avoid hyponatremia could either take the Neurontin tablet or liquid (rather than the capsule) and should be careful that their total daily consumption of liquids is not excessive.

Exactly how much liquid is excessive is something that patients should discuss with their physician. The first step in preventing any problem with hyponatremia is for the patient to be very precise as to how much liquid he/she is taking. Blood levels of sodium should also be checked periodically.

Pregabalin (Lyrica) is often started at 50 mg three times a day and may be increased to 100 mg three times a day. It has been shown to be helpful for some patients with diabetic nerve pain, post-herpetic nerve pain and fibromyalgia and is also used for patients with trigeminal neuralgia. Pregabalin is similar to gabapentin and it is likely to have a similar effect in patients with trigeminal neuralgia.


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 Lamotrigine (Lamictal) for trigeminal neuralgia

Lamotrigine (Lamictal) is often very effective in relieving the pain of trigeminal neuralgia. It can be added to Lyrica or gabapentin. Lamictal can sometimes cause a rash. If this occurs, it must be stopped. Its dose is built up gradually and is usually started at 25 mg once or twice a day.

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 Other medicines for trigeminal neuralgia

There are other medicines that can be used either alone or in combination. These are usually less effective than carbamazepine or oxcarbazepine. They include levetiracetam (Keppra), clonazepam (Klonopin), topiramate (Topamax), phenytoin (Dilantin), and baclofen (Lioresal). Klonopin is also used to relieve anxiety. Topamax is often given to prevent migraine headaches. Dilantin was one of the first medicines used to treat trigeminal neuralgia. It has more side effects than most of the other medicines and is rarely used on a long-term basis any more. Fosphenytoin (Cerebyx), which is very similar to phenytoin is given intravenously. It may be helpful for very severe, persistent pains. This must be given in a hospital or out-patient facility under medical supervision. Continuous monitoring of electrocardiogram and blood pressure is needed. Baclofen, a muscle relaxer, is often given in patients with spasticity, many of whom also have multiple sclerosis and has also been shown to help some patients with trigeminal neuralgia.


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 Are narcotics helpful for trigeminal neuralgia?

Narcotic pain-relieving medicines, such as morphine or codeine, are not usually helpful for treating trigeminal neuralgia. These medicines often cause drowsiness and nausea and make it difficult for patients to tolerate the other medicines that are more effective for treating trigeminal neuralgia.

There is increasing recognition that opioid pain relieving drugs (morphine, codeine and oxycodone) are widely diverted and improperly used, and the widespread use of these drugs has resulted in a national epidemic of opioid overdose, deaths and addictions. (N Engl J Med 2016;374:1253-63). Dr. Ronald Brisman continues to believe that opioid drugs are not a good choice for relieving pain of trigeminal neuralgia.


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 Do medicines for trigeminal neuralgia cause osteoporosis?

Osteoporosis, or porous bones, is a condition which may predispose to bone fractures. Many of the anticonvulsant medicines (medicines to prevent seizures, such as Tegretol or Trileptal) that are used to treat trigeminal neuralgia may increase the tendency to develop osteoporosis. There are many other factors that can increase the chances that a patient may develop osteoporosis. These include a positive family history, postmenopausal women, white skin color, light weight, cigarette smoking and a sedentary life style. As there are ways to measure and help prevent or treat osteoporosis, patients who take antiseizure medicines for their trigeminal neuralgia should consider discussing this with their family doctor who is managing their general medical care.

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