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Treating Trigeminal Neuralgia

   There is a growing arsenal of ways to treat TN, including medications and surgical treatments. The first universally accepted treatment option is usually through medications. Surgical procedures are used for those patients who are unable to tolerate the medications, exhibit serious side effects, or if the medications do not control the problem. Medications are initially effective for many patients, but over a period of time their effectiveness may diminish and a surgical procedure required.
        During all phases of medical treatment, patients need good communication with their physician and nurse to monitor their medication and response. The patient must understand the need to maintain a therapeutic blood level of medication for effective pain relief. Taking the medications irregularly is not effective.
        Abrupt withdrawal of medications can cause serious side effects. Analgesics (i.e. aspirin, Tylenol, etc.) are not effective in addressing the pain of TN as it is of lightning-like intensity and the attacks are of brief duration. In general, narcotics have not been recommended as first line therapy for TN, as they have not been found to be effective for the characteristics of TN pain. While there are no controlled studies in TN, there is recent information that narcotics may be helpful in other painful conditions that have similar pain characteristics.
        The primary drug used to treat TN is carbamazepine. It is also used to treat seizures. Initial relief is so readily achieved that many physicians consider its use as a means to confirm the diagnosis of TN. The drug is introduced slowly and increased to a level where the patient is pain-free or side effects occur.
        Carbamazepine is available as Tegretol. A newer medication is oxcarbazepine, available as Trileptal. Extended release carbamazepine is available as Carbatrol and Tegretol XR.

        In the last several years, oxcarbazepine (Trileptal) has been used more frequently as a first line drug for TN. It is structurally related to carbamazepine, and may be preferable due to a more favorable side effect profile.  Other medications used in the treatment of TN may include baclofen (Lioresal), gabapentin (Neurontin), clonazepam (Klonopin), sodium valporate (Depakote), lamotrigine (Lamictal), and topiramate (Topamax).      

According to the petition, the number of suicides reported by Pfizer to the FDA jumped to 17 in the first six months of 2003, the latest information available, compared with a total of eight from 1998 through 2002. Drug companies are required by law to file such reports.

Mr. Finkelstein said he filed the petition because the "sudden uptick in reports" meant that FDA officials "have enough in their own data set to take action without any delay."

In a statement, Pfizer said it remains "confident of the safety and effectiveness of this product" and it would be "extremely irresponsible if the petition or accompanying publicity were used to promote the false impression that there is a causal link between Neurontin and suicide." The company said it hasn't seen the petition, but is aware that law firms are soliciting as clients current and former Neurontin patients.

Neurontin brought Pfizer revenue of $2.7 billion in 2003. The drug is sold in more than 100 countries and has been prescribed to about 10 million patients since it was launched in 1994.

Last week, Pfizer unit Warner-Lambert pleaded guilty to illegally promoting the drug for a variety of uses not approved by the FDA, and agreed to pay a total of $430 million in fines and damages. Neurontin originally was approved as a supplemental antiseizure treatment for epilepsy, but it is widely used "off label" for a variety of other conditions, including migraines, bipolar disorder and pain.

An FDA spokesman said the agency "looks forward to reviewing and responding" to the petition.

The agency frequently doesn't regard information from its own adverse-event reporting system as a definitive measure of risk. In addition, it often is tough for regulators and drug companies to clearly tie suicidal behavior to a specific medication, particularly in patients suffering from psychiatric disorders.

In the early 1990s the FDA rejected a petition from a group funded by the Church of Scientology to ban the antidepressant Prozac because of concerns it could lead to suicidal behavior and other bad effects, and an agency advisory committee voted against a label warning. That issue has re-emerged recently because of concerns that some antidepressants may somehow be tied to suicidal tendencies in young people. The FDA recently asked drug makers to add a new, generally worded warning to their labels urging doctors and others to closely monitor all patients on antidepressants.

10 Neurontin News

May 20, 2004 Pfizer Inc.'s drug Neurontin, at the heart of a controversy over an illegal marketing scheme, is facing a new challenge: a petition asking the Food and Drug Administration to act on claims that it may be tied to suicidal behavior.

The petition to the FDA came from Finkelstein & Partners, a personal-injury law firm in Newburgh, N.Y., that has filed three suits against Pfizer on behalf of people who committed suicide or attempted it. The suits allege that Neurontin played a role in the suicidal behavior.

Andrew Finkelstein, the managing partner at the firm, says he plans to file hundreds of more suits. Largely by running television ads raising questions about the drug, he has accumulated a list of 160 suicides and 2,000 attempts by people who were taking Neurontin for a variety of ailments, he says.

The petition to the FDA, however, is based on the FDA's own adverse-event reporting database, not Mr. Finkelstein's list of clients. It asks the agency to add a warning to the labeling for Neurontin and to send a letter to doctors and other health-care professionals.

According to the petition, the number of suicides reported by Pfizer to the FDA jumped to 17 in the first six months of 2003, the latest information available, compared with a total of eight from 1998 through 2002. Drug companies are required by law to file such reports.

Mr. Finkelstein said he filed the petition because the "sudden uptick in reports" meant that FDA officials "have enough in their own data set to take action without any delay."

In a statement, Pfizer said it remains "confident of the safety and effectiveness of this product" and it would be "extremely irresponsible if the petition or accompanying publicity were used to promote the false impression that there is a causal link between Neurontin and suicide." The company said it hasn't seen the petition, but is aware that law firms are soliciting as clients current and former Neurontin patients.

Neurontin brought Pfizer revenue of $2.7 billion in 2003. The drug is sold in more than 100 countries and has been prescribed to about 10 million patients since it was launched in 1994.

Last week, Pfizer unit Warner-Lambert pleaded guilty to illegally promoting the drug for a variety of uses not approved by the FDA, and agreed to pay a total of $430 million in fines and damages. Neurontin originally was approved as a supplemental antiseizure treatment for epilepsy, but it is widely used "off label" for a variety of other conditions, including migraines, bipolar disorder and pain.

An FDA spokesman said the agency "looks forward to reviewing and responding" to the petition.

The agency frequently doesn't regard information from its own adverse-event reporting system as a definitive measure of risk. In addition, it often is tough for regulators and drug companies to clearly tie suicidal behavior to a specific medication, particularly in patients suffering from psychiatric disorders.

In the early 1990s the FDA rejected a petition from a group funded by the Church of Scientology to ban the antidepressant Prozac because of concerns it could lead to suicidal behavior and other bad effects, and an agency advisory committee voted against a label warning. That issue has re-emerged recently because of concerns that some antidepressants may somehow be tied to suicidal tendencies in young people. The FDA recently asked drug makers to add a new, generally worded warning to their labels urging doctors and others to closely monitor all patients on antidepressants.

Introduction

Trigeminal Neuralgia (TN), or "Tic Douloureux" is characterized by intermittent, shooting pain in the face. TN is diagnosed by clinical symptoms, but all patients should have an MRI scan of the head to evaluate for any intracranial abnormality. The most common cause of Trigeminal Neuralgia is an enlarged looping artery or vein pressing on the Trigeminal nerve at the base of the brain. Other less frequent causes are multiple sclerosis or a brain tumor, both of which can usually be identified by MRI scan when they exist. Tumors require immediate surgical attention, whereas face pain caused by multiple sclerosis can be treated the same as Trigeminal Neuralgia except that microvascular decompression is not feasible. Face pain which is secondary to a dental procedure, or which is classified as "atypical facial pain," is different from Trigeminal Neuralgia and the following comments may not be applicable.

The initial treatment for Trigeminal Neuralgia should be medical. The most effective drugs are carbamazepine (Tegretol®) and gabapentin (Neurontin®). They should be started at a low dose and gradually increased with the ideal dosage being that which controls the pain but does not cause side effects. If during therapy the pain subsides completely for four weeks, it is reasonable to gradually reduce the dosage and see if the Trigeminal Neuralgia has gone into remission. If the pain recurs the drug can be re-instituted.

Once the initial pain is controlled it is important to consider the natural history of Trigeminal Neuralgia in order to understand long term management. (see below)

For those patients whose symptoms cannot be controlled medically without side effects such as nausea, ataxia, or mental dulling, or who desire long term relief without medication, it is wise to consider surgical options. The surgical options can be divided into two categories: non-destructive procedures and destructive procedures. (see below)

Natural History

Trigeminal Neuralgia can occur at any age, but usually has its onset in individuals over fifty. It is common for the pain of Trigeminal Neuralgia to come and go spontaneously (frequently referred to as waxing and waning), which often makes it difficult to know whether any specific treatment is beneficial.

Unfortunately, over time the pain of Trigeminal Neuralgia usually becomes more severe and more frequent, requiring higher dosage and more continuous use of medications. As a result, many patients whose pain was initially well controlled with medication find over time that they must increase to toxic levels in order to control their pain. At this point, unless they are willing to exist with the pain or in a toxic state, they require surgical intervention.

An Alternate Strategy

Instead of waiting for the pain to become intractable or the medications toxic, an individual with trigeminal neuralgia has the option to request early surgery. This has a number of potential advantages:

· Avoid years of medication and intermittent pain

· Avoid facing surgery when old or infirm

· If the person has a vascular loop, early microvascular decompression will increase the possibility of a successful operation with decreased risk of recurrence (evidence suggests better outcomes and lower recurrence rate the shorter the interval between onset of symptoms and nerve decompression)

How To Find Out If You Have a Vascular Loop

The conventional MRI scans used to rule out the presence of a brain tumor or multiple sclerosis as a cause of a patients face pain are not adequate to visualize the trigeminal nerve or an associated blood vessel. Fortunately, the continued improvement in MRI neuro-imaging now makes it possible to visualize both. The technique, which is called 3-D volume acquisition, is performed with contrast injection and utilizes thin cuts (0.8mm), without gaps similar to what was developed for MRI angiography and venography. The trigeminal nerve is easily visualized in the axial plane when the MRI series is centered at the midpoint of the fourth ventricle. To ensure an adequate evaluation, the nerve should be seen on three adjacent cuts. Early studies indicate that when an offending vessel is present it will be detected 80% of the of the time. With continued imaging improvements this percentage will definitely increase.

Surgical Options: Non-Destructive Procedures

The only non-destructive procedure which reliably relieves the symptoms of Trigeminal Neuralgia is Microvascular Decompression (MVD). This involves surgical exploration with the operating microscope and visualization of the junction where the Trigeminal nerve enters the base of the brain, followed by coagulation or moving and padding away any compressing blood vessels. The advantage is pain relief without numbness in the majority of patients, which usually lasts indefinitely. If the pain recurs after a MVD, which it does in 10-15% of patients, it can usually be controlled with low dose Tegretol® or Neurontin®. If the pain continues, it will require a repeat MVD or one of the destructive procedures.

Surgical Options: Destructive Procedures

There are multiple destructive procedures which are beneficial in the treatment of Trigeminal Neuralgia. The most common of which are glycerol injections, gamma knife radiation, electrocoagulation, and balloon compression. These procedures are all based on interrupting the pain by partial damage to Trigeminal nerve fibers. Generally the more numbness they produce, the longer they last. The specific advantages and disadvantages need to be discussed with the surgeon performing the procedure. These procedures are recommended for patients who have failed MVD or are not candidates for major surgery.

Comments

Treatment is always individualized.  All of the options above should be considered in consultation with a neurosurgeon familiar in their use.

Recommendations

Based on the data currently available, and in an effort to maximize quality of life, we recommend the following:

Patients with less than 10 year life expectancy

Refer for destructive procedure if pain not controlled medically without significant side effects

Patients with more than 10 but less than 20 year life expectancy

Consider destructive procedure

May abolish need for continued increasing medications

Will make medical therapy easier even if fails

Patients with more than 20 year life expectancy

Perform thin cut MRI with 3-D Volume Acquisition

If vessel present recommend MVD

Consideration needs to be given to current life expectancy charts at time of implementation. At this time life expectancy is shown below:

(data from IRS Publication 590, Appendix E, Table 1, December 12, 1999)

When a destructive procedure is required, Gamma Knife stereotactic radiosurgery is the procedure of choice because it is least invasive and has the lowest risk of numbness or other side effects, while producing excellent pain relief in most patients with a low incidence of recurrence.