Yourlawyer.com (Epilepsy Drugs News)

Another Valproate Study Sees Problems for Developing Fetus

Wed, 22 Jul 2009 00:00:00 -0700

Children exposed to valproate in-utero may exhibit lower IQs as toddlers than children whose mothers took other epilepsy drugs, according to the results of an interim study conducted by scientists at the University of Liverpool.

Valproate is an epilepsy drug sold under the brand names Depacon and Depakene. In the past, various studies have raised concerns about the safety of valproate during pregnancy. Just last December, we reported that a British study had found that children whose mothers had taken valproate during pregnancy were seven times more likely to develop autism than those not exposed to any epilepsy medication. The increased risk was not seen with other epilepsy drugs included in the study.

Another study published in Neurology last year found that women taking valproate along with the migraine medication Topamax were 11 times more likely to give birth to a baby with birth defects than those taking Topamax alone. Defects seen in that study included genital birth defects in male babies, a hole above the buttocks, a flattened head, toe webbing, clicky hips and immature hip joints.

Previous research has also shown that valproate is associated with an increased risk of birth defects such as heart defects and spina bifida.

According to a press release posted on Science Daily, this latest valproate study, conducted in collaboration with Emory University in the US and the Central Manchester University Hospitals NHS Foundation Trust in the United Kingdom UK), tested more than 300 three-year-olds in the UK and US, whose mothers took one of four anti-epilepsy drugs during pregnancy. The results also took dosage, duration of pregnancy and mother’s consumption of folic acid while pregnant, into account.

The preliminary findings suggest that children exposed to the valproate had lower IQ results than children exposed to the other drugs, regardless of the mother’s IQ. The children exposed to valproate had IQs that were six to nine points lower than average.

The researchers cautioned that pregnant women taking valproate not stop without speaking to their doctor, as the affects of suffering a seizure can also pose a risk for both mother and unborn child. Instead, they said women need to be aware of the risks so that they can make informed choices with the help and advice of experts.

Suicide Warnings Approved for Epilepsy Drugs

Wed, 06 May 2009 00:00:00 -0700

Federal regulators have approved new suicide warnings for more than two dozen epilepsy drugs. The Food & Drug Administration (FDA) had ordered the label update last December, when it issued a public-health advisory regarding the association between epilepsy drugs and suicidal thoughts and behavior.

The new suicide warnings will appear on the labeling of Carbatrol, Celontin, Depakene, Depakote ER, Depakote sprinkles, Depakote tablets, Dilantin, Equetro, Felbatol, Gabitril, Keppra, Keppra XR, Klonopin, Lamictal, Lyrica, Mysoline, Neurontin, Peganone, Stavzor, Tegretol, Tegretol XR, Topamax, Tranxene, Tridione, Trileptal, Zarontin, Zonegran, as well as their generic equivalents, the FDA said.

In addition to epilepsy, some of these drugs are used to treat psychiatric disorders, migraine headaches and other conditions.

As we reported in December, the new warnings resulted from the FDA's review of 199 clinical trials of 11 antiepileptic drugs which showed that patients receiving antiepileptic drugs had almost twice the risk of suicidal behavior or thoughts (0.43 percent) compared to patients receiving a placebo (0.24 percent). This difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with antiepileptic drugs instead of placebo, the agency said.

Since December, the agency has been working with drug makers to determine the appropriate labeling. The revised labels were approved on April 23, the FDA said.

In addition to the revised labels, new comprehensive Medication Guides have been approved for Lamictal, Lyrica, Topamax, Zonegran and Keppra. The FDA said comprehensive Medication Guides are being developed for the other drugs and should be available by the end of 2009.

According to the FDA, if suicidal thoughts or behavior emerges in patient during treatment with any of the affected epilepsy drugs, prescribers should consider whether these symptoms may be related to the illness being treated. All patients who currently are taking or starting on any antiepileptic drug for any indication should be monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

Valproate Shouldn't be Taken by Pregnant Women, Medical Groups Say

Tue, 28 Apr 2009 00:00:00 -0700

The epilepsy drug valproate (Depacon) should not be taken by pregnant women, according to new guidelines issued by American Academy of Neurology and the American Epilepsy Society. According to a report on medpagetoday.com, the groups have also recommended that expectant mothers who need them take only one epilepsy medication at a time.

The groups, which published the new guidelines simultaneously in the journals Neurology and Epilepsia, said that in general, epileptic women can have safe pregnancies. "These guidelines show that women with epilepsy are not at a substantially increased risk of having a cesarean section, late pregnancy bleeding, or premature contractions or premature labor or delivery," Cynthia Harden, M.D., of the University of Miami, lead author of the guidelines, said during a briefing announcing the guidelines yesterday.

However, the groups have warned pregnant women to avoid the drug valproate if possible. According to WebMD, in making the recommendation, the groups cited the drug's association with major birth defects, including cleft palate and spinal bifida.

As we've been reporting for the past several months, various studies have shown valproate to be harmful to a developing fetus. Earlier this month, a study conducted by scientists at Emory University found that toddlers exposed to valproate in utero had lower IQs than those whose mothers took other epilepsy drugs. In December, we reported that a British study had found that children whose mothers had taken valproate during pregnancy were seven times more likely to develop autism than those not exposed to any epilepsy medication. The increased risk was not seen with other epilepsy drugs included in the study.

Another study published in Neurology last year found that women taking valproate along with the migraine medication Topamax were 11 times more likely to give birth to a baby with birth defects than those taking Topamax alone. Defects seen in that study included genital birth defects in male babies, a hole above the buttocks, a flattened head, toe webbing, clicky hips and immature hip joints.

The guidelines also recommend that pregnant women taking other epilepsy drugs use only one. Taking more than one medication raises the risk of birth defects compared with taking only one medication, the guidelines said.

Finally, the groups said pregnant women may also want to avoid taking phenytoin (Dilantin) and phenobarbital, as they too have been linked to lower IQs in children, WebMD said.

The guidelines also pointed out that primidone (Mysoline) and levetiracetam (Keppra) were detected in breast milk at various levels "that may be clinically important," WebMD said. Valproate, phenobarbital, phenytoin, and carbamazepine ( Tegretol) were not, the panel says.

At yesterday's briefing, Harden said the groups found no evidence "one way or another" that exposure to the drugs through breast milk was harmful, but suggested mothers and their doctors take this information into consideration when making decisions about breast feeding.

Other guidelines issued by the groups included:

Pregnant women with epilepsy should have their blood tested regularly, as pregnancy has been shown to lower the levels of anti-epileptic drugs in the blood, which may put women at risk of seizures.
Women planning to become pregnant should take at least 400 micrograms of folic acid a day, as supplementation has been shown to be "possibly effective" in preventing major birth defects.
Smoking during pregnancy may increase substantially the risk of premature contractions and premature labor and delivery during pregnancy.

According to WebMD, the groups are recommending that epileptic women who wish to become mothers consult their doctors about seizure medications at least six months before becoming pregnant. They stressed that women should not stop taking any epilepsy medication without first talking to their physician.

Valproate During Pregnancy Linked to Children with Lower IQs

Thu, 16 Apr 2009 00:00:00 -0700

Valproate (sold under the brand names Depacon and Depakene) taken during pregnancy may cause children to have lower IQs, according to a new study published in The New England Journal of Medicine. According to a report on Reuters.com, toddlers exposed to valproate in utero had IQs that were 6 to 9 points lower than children whose mothers took other epilepsy medications.

The valproate IQ study, conducted by scientists at Emory University, is just the latest to show that the anti-seizure medication is harmful to a developing fetus. Just last December, we reported that a British study had found that children whose mothers had taken valproate during pregnancy were seven times more likely to develop autism than those not exposed to any epilepsy medication. The increased risk was not seen with other epilepsy drugs included in the study.

Another study published in Neurology last year found that women taking valproate along with the migraine medication Topamax were 11 times more likely to give birth to a baby with birth defects than those taking Topamax alone. Defects seen in that study included genital birth defects in male babies, a hole above the buttocks, a flattened head, toe webbing, clicky hips and immature hip joints.

Previous research has also shown that valproate is associated with an increased risk of birth defects such as heart defects and spina bifida.

According to the Associated Press, researchers in the Emory study followed pregnant women in the United States and United Kingdom between 1999 and 2004. The results are based on about 260 of their children. The average IQ of toddlers born to women who took valproate was 92, while the scores of those exposed to other epilepsy drugs, including lamotrigine, phenytoin, and carbamazepine, ranged from 98 to 101. An IQ of 100 is considered average.

The higher the dosage of valproate a woman had taken, the lower the IQ of the child, the researchers found. For the other drugs, dosage levels made no significant difference.

The implications of this study are important. According to Reuters.com, about 25,000 babies are born to epileptic mothers every year. If a pregnant woman takes valproate, it is often because it is the only drug that works for her.

An editorial accompanying the Emory study in the New England Journal of Medicine advised that women taking valproate who want to get pregnant should plan their pregnancies carefully and consult with a doctor. Switching drugs after a woman realizes she is pregnant is unlikely to reduce the risk of birth defects. And abruptly stopping the medication may endanger the mother and the fetus, the editorial said.

Zonegran Linked to Blood Disorder

Mon, 23 Feb 2009 00:00:00 -0800

The epilepsy drug zonisamide, sold both generically and under the brand name Zonegran, can cause a serious blood disorder called metabolic acidosis, the Food & Drug Administration (FDA) warned today. The agency said it is working with the makers of zonisamide to revise the product labeling to reflect this new risk.

According to the FDA, metabolic acidosis is a disturbance in the body's acid-base balance that results in excessive acidity of the blood. Metabolic acidosis can result in hyperventilation, and non-specific symptoms such as fatigue and anorexia, or more severe symptoms including cardiac arrhythmias or stupor. Chronic metabolic acidosis can have adverse effects on the kidneys and on bones, and can retard growth in children.

Patients with predisposing conditions or therapies, including renal disease, severe respiratory disorders, diarrhea, surgery, ketogenic diet, or certain other drugs may be at greater risk for developing metabolic acidosis following treatment with zonisamide. The risk of zonisamide-induced metabolic acidosis appears to be more frequent and severe in pediatric patients, the FDA said.

According to a review of updated clinical data, the development of metabolic acidosis in patients taking Zonegran and generic equivalents generally appears to be dose-dependent and can occur at doses as low as 25 mg daily, the FDA said. Zonegran-induced metabolic acidosis generally occurs early in treatment, although it can occur at anytime.

The FDA has recommended that healthcare professionals measure serum bicarbonate before starting treatment and periodically during treatment with Zonegran, even in the absence of symptoms. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Zonegran, and modifying the patient's antiepileptic treatment as appropriate. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Zonegran, and modifying the patient's antiepileptic treatment as appropriate.

If the decision is made to continue patients with metabolic acidosis on Zonegran, then alkali treatment should be considered, the FDA said.

Zonisamide is approved as an adjunct therapy to treat partial seizures in adults. It is sold as Zonegran by Eisai Co Ltd, and in generic form by Teva Pharmaceutical Industries Ltd., Mylan Inc., Novartis AG's Sandoz unit and Watson Pharmaceuticals Inc.

Valproate Use During Pregnancy Linked to Autism

Tue, 02 Dec 2008 00:00:00 -0800

Mothers who take the epilepsy drug valproate (sold under the brand names Depacon and Depakene) during pregnancy may face an increased risk of having a child who will develop autism, a new study has found.. The British researchers who worked on the study, published in the journal Neurology, have recommended that pregnant women taking valproate be informed of the possible risks of autism and discuss the issue with their doctors.

The valproate study, conducted by researchers at the Liverpool and Manchester Neurodevelopment Group, involved 632 children and a variety of epilepsy drugs. None of the children in the study had any known family history of autism. According to Science Daily, 64 children were exposed in utero to valproate, 44 to lamotrigine (brand name Lamictal), 76 to carbamazepine (sold under a variety of brand names, including Tegretol) and 65 to other epilepsy drugs.

Among the children in the study, nine have been diagnosed with autism and one has shown symptoms of the disorder, Science Daily said. Of those children, seven were exposed to an epilepsy drug before birth, and four of those had been exposed to valproate. A fifth child's mother took a combination of valproate and lamotrigine, Science Daily said.

The study indicates that children born to women who took valproate during pregnancy were seven times more likely to develop autism than those not exposed to any epilepsy medication. The increased risk was not seen with the other epilepsy drugs, Science Daily said.

The researchers who conducted the valproate autism study cautioned that their findings were preliminary, but still significant. "The potential risk for autism in this study was substantial for children whose mothers took valproate while pregnant, but more research needs to be done since these are early findings," study author Gus Baker, PhD, FBPsS, of the University of Liverpool, said in a press release. "However, women who take valproate while pregnant should be informed of the possible risks of autism and are encouraged to discuss them with their doctor."

This is not the first time valproate use during pregnancy has been linked to problems in children. Earlier this year, another study published in Neurology found that women taking valproate along with the migraine medication Topamax were 11 times more likely to give birth to a baby with birth defects than those taking Topamax alone. Defects seen in that study included genital birth defects in male babies, a hole above the buttocks, a flattened head, toe webbing, clicky hips and immature hip joints.

Previous research has also shown that valproate is associated with an increased risk of birth defects such as heart defects and spina bifida.

Advisory Panel Rejects 'Black Box' Warnings of Suicide Risk on Epilepsy Drugs

Fri, 11 Jul 2008 00:00:00 -0700

An expert advisory panel refused a Food & Drug Administration (FDA) proposal to place a “Black Box”—the agency’s strongest warning—warning about suicide risks on 11 common epilepsy drugs, including Neurontin, Lyrica, and Topamax. All the drugs cited are approved to treat epilepsy, but many are prescribed for other problems, including migraines and bipolar disorder. The FDA often follows the recommendations of its advisory panel, but is not required to.

Following an FDA analysis of some 200 studies, it concluded patients taking the epilepsy drugs had nearly double the risk of suicidal thoughts or behaviors. Earlier this week, FDA officials proposed inclusion of the black box to force companies to issue new medication guides warning patients of potential risks. Eight of the 11 drugs showed an increased risk, while three did not; however, the FDA is proposing warnings on all of the drugs and possibly some older epilepsy drugs. Other drugs include Lamictal, valproate, oxcarbazepine (sold under the brand name Trileptal), Tegretol, tiagabine, zonisamide, levitiracetam, and felbamate. Of the 43,000 patients studied, 30 taking epilepsy drugs attempted suicide and four completed suicide.

Experts continue to urge the FDA to place some type of new warnings on the drugs. "We are looking at a signal that I feel is an important one for the field to be aware of," says Andrew Winokur, MD, a professor of psychiatry and psychopharmacology at the University of Connecticut Health Center.

The FDA’s proposal for a warning sparked controversy as soon as it was announced and the FDA was also criticized in 2005 after placing similar warnings on antidepressant medications when evidence suggested some of the drugs could lead to suicidal behavior. FDA critics said the warnings drove patients away from necessary treatment. The FDA later revised its warnings.

Some experts fear the FDA is making a similar move by suggesting broad warnings for drugs that may not have been studied or analyzed for suicide risk. "We have to be very careful about scaring the patients into not taking these drugs, and I think we have to be very thoughtful about that," says Rochelle Caplan, MD, a professor of psychiatry at University of California Los Angeles and a member of the expert panel. "Overwarning actually has the potential to negatively impact patient care," said Christopher Wholberg, a global medical team leader for Pfizer, which makes Lyrica and Neurontin.

Researchers remain unclear as to the cause of the link between epilepsy drugs and suicidal thought and behavior. "We don't quite know what the phenomenon we're looking at is," says Robert Temple, MD, director of the FDA's office of drug evaluation. "If something is important it gets noticed better if you put a box around it. It doesn't mean don't use this drug. It means pay attention," Temple says. FDA advisors disagreed, saying there was insufficient evidence to support stark warnings that could discourage patients and their doctors from using them. "That's put there to bring attention to it and it comes with a lot of baggage with it," says Larry Goldstein, MD, a professor of Medicine at Duke University and chair of the advisory panel.

Epilepsy Drugs Targeted for Black Box Suicide Warning

Tue, 08 Jul 2008 00:00:00 -0700

Federal regulators want the makers of epilepsy drugs to add a black box warning to their labels about their association with suicidal thoughts and behavior. The Food & Drug Administration (FDA) is set to ask an outside advisory panel for its recommendations on the proposed black box at a meeting this Thursday.

In total, 11 epilepsy drugs could get the new black box warning - the FDA's strongest safety notice. They include:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

The FDA began investigating if epilepsy drugs posed any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The studies tracked almost 28,000 people given epilepsy medications and another 16,000 given dummy pills.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

According to the FDA, three of the 11 drugs studied showed no clear signal of suicidal problems. However, the agency is still leaning towards including the warning on all the drugs, as sample sizes in some of the studies might have been too small to accurately assess suicide risks. One of the issues the agency will ask the panel to address at Thursday's meeting is whether all of the drugs, or just some of them, should be subjected to the black box.

The FDA is not bound to follow the recommendations of its advisory panels, but it usually does so.

Neurontin Should Have Had Depression Warning, Neurologist Says

Fri, 20 Jun 2008 00:00:00 -0700

A British neurologist says he advised the maker of Neurontin to include a warning on its label about its potential to cause depression and aggression, but he was ignored. According to The Wall Street Journal, the neurologist, Michael R. Trimble from the University of London, was testifying at a hearing to decide whether civil cases brought against Pfizer alleging suicides linked to Neurontin can proceed.

Neurontin was approved for sale in the mid-1990s as a treatment for epileptic seizures. While Neurontin is approved for the treatment of epilepsy, it has been used "off-label" to treat a wide range of other conditions, including bipolar disorder, ADHD and Migraines.

Earlier this month, the U.S. Food & Drug Administration (FDA) directed the makers of 11 epilepsy drugs, including Neurontin, to add new warnings to their labels about the drugs' potential to cause suicidal thoughts and behavior. The FDA began investigating if epilepsy drugs posed any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The studies tracked almost 28,000 people given epilepsy medications and another 16,000 given dummy pills.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

According to The Wall Street Journal, Dr. Trimble testified that in 1995 and 1996, he was hired to write two confidential reports for Parke-Davis -- now a unit of Pfizer -- because the company "was concerned about psychosis" as a potential side effect of Neurontin. Dr. Trimble said he was unable to find a link to psychosis, but did find one between the drug and depression and aggression. For the 1996 report, Dr. Trimble analyzed nine patients who had no previous symptoms of the side effects. Five of those patients exhibited depression and aggression after they had begun taking Neurontin. Dr. Trimble said he recommended to the company that the drug "should carry some kind of warning" for susceptible patients.

Dr. Trimble's testimony was part of a hearing that was jointly held by judges for U.S. District Court in Boston and a New York state court who are hearing similar cases. According to The Wall Street Journal, various lawsuits have been consolidated in the federal court in which plaintiffs allege more than 100 suicides were connected to Neurontin usage.

New Suicide Warning for Epilepsy Drugs

Thu, 12 Jun 2008 00:00:00 -0700

United States drug reviewers just announced that epilepsy drugs are associated with a higher risk of suicidal thoughts and behavior. The analysis was released this week and confirmed earlier findings. "The effect appears consistent among the group of 11 drugs" that were reviewed, according to a summary from statistical reviewers at the Food and Drug Administration (FDA). In the review dated May 23, the FDA staff said that there were about two more cases of suicidal thoughts and behavior per every 1,000 patients given the drugs versus those given a placebo. In January, the FDA released similar findings, according to FDA spokeswoman Sandy Walsh.

The epilepsy drugs include Pfizer Inc.'s Lyrica, GlaxoSmithKline's Lamictal, Johnson & Johnson's Topamax, and Abbott Laboratories Inc.'s Depakote. FDA officials said that they are working with the drug makers to add information about the suicidal behavior risk to the prescribing instructions for these drugs. Also, a panel of outside advisers to the FDA is scheduled to discuss the issue next month, on July 10.

The FDA staff reviewed 199 trials involving about 44,000 patients who were given either an epilepsy drug or a placebo. Some of the epilepsy medicines are also approved for depression, migraines, and other conditions. As a result, four patients given drug treatment committed suicide, compared with zero suicides in the group who received the placebo, according to the FDA staff review. Generally, approximately 0.4 percent of drug-treated patients reported suicidal thoughts or actions, compared with 0.2 percent of placebo patients.

In January, the FDA warned that all patients taking epilepsy drugs should be closely monitored for changes in behavior that could indicate either suicidal thoughts or behaviors or depression. Kara Russell, spokeswoman at Johnson & Johnson's Ortho-McNeil Neurologics Inc. unit—the group that makes Topamax—said the company was reviewing the FDA's report and confirmed that language about possible suicide behaviors or attempts "has existed in our labeling since the beginning." UCB SA spokeswoman, Andrea Levin, said prescribing instructions for its epilepsy drug, Keppra, already included data on suicidal behavior reported in clinical trials. Levin advised that UCB SA would comply if the FDA asked for changes.

A Glaxo analysis of Lamictal found a trend for suicidal thoughts and behavior that was similar to that found in the FDA analysis, according to company spokeswoman, Holly Russell. Glaxo is currently working with regulators to update the drug label, she said. Abbott spokeswoman Laureen Cassidy said the company would work with the FDA to implement any changes requested for the class of drugs.

Epilepsy is a neurological condition that, from time-to-time produces brief disturbances in normal electrical brain functions. When someone has epilepsy, normal electrical brain patterning may be interrupted by intermittent bursts of electrical energy that are much more intense than usual. These interruptions and bursts may affect a person's consciousness, bodily movements, or sensations for a short time and are called epileptic seizures and are why epilepsy is sometimes called a seizure disorder. The bursts may occur as partial seizures affecting just one area of the brain or can be generalized, affecting nerve cells throughout the brain.

Epilepsy Drugs to Get Suicide Warnings, FDA Confirms

Fri, 06 Jun 2008 00:00:00 -0700

US regulators are very close to finalizing new suicide warnings for 11 epilepsy drugs, The Wall Street Journal reported today. This past January, the Food & Drug Administration (FDA) issued an Early Communication announcing a safety review of the epilepsy drugs after a study showed they increased patients' risk of suicidal thoughts and behavior.

The 11 epilepsy drugs slated for a new suicide warning are:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

In addition to treating epilepsy, the anti-seizure medications are used for a variety of other illnesses, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder that themselves carry a risk of suicide.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

In an interview with The Wall Street Journal, Russell Katz, director the FDA's neuropharmacological drug division confirmed the suicide warnings are coming. "We are working on the labeling changes that we want to get to the companies," he said. An FDA advisory panel is slated to take up the issue of epilepsy drugs and suicide on July 10, but the Journal speculated the new warnings could come even sooner than that.

At least one drug maker, Pfizer Inc., is less than pleased at this development. Pfizer disputed the FDA's analysis in a forum this week sponsored by the Epilepsy Study Consortium in New York. Pfizer especially disputes the inclusion of Lyrica - one of the company's biggest growth drivers -on the FDA's warning list. Pfizer said that Lyrica accounted for only 6.3% of the total 142 suicidal events cited by the FDA analysis. But the FDA is sticking to its guns, and the new suicide warning will apply to all 11 epilepsy drugs.

Most other epilepsy drug makers are resigned to the label changes, according to the Journal. GlaxoSmithKline, the maker of Lamictal, approached the FDA this year to volunteer changes regarding possible suicidal-behavior risks. Other drug makers may have chosen not to challenge the FDA on suicide warnings because their medications are no longer as lucrative as they once were, as patents on many epilepsy drugs have, or are close to, expiring.

Epilepsy Drugs May Get New Suicide Warnings, In Spite of Pressure From Big Pharma

Wed, 04 Jun 2008 00:00:00 -0700

Federal regulators are considering new suicide warnings for some epilepsy drugs, but the pharmaceutical companies that make the medications are desperately trying to quash the action, The Wall Street Journal reported today. The drug makers, including GlaxoSmithKline and Pfizer, Inc., made their case to the Food & Drug Administration (FDA) at a closed meeting on Monday. How successful the industry was may become apparent next month, when the FDA holds a public meeting to discuss possible warnings for epilepsy drugs.

The FDA began investigating if epilepsy drugs pose any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The antiepileptic medications studied by the FDA included:

Carbamazepine(marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

The FDA studies tracked almost 28,000 people given epilepsy medications and another 16,000 given dummy pills. According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. In January, the findings prompted the FDA to issue an early communication warning about the drugs' potential for suicidal thoughts and behavior.

An FDA advisory panel is slated to take up the issue of epilepsy drugs and suicide in July, and it is very possible the panel will recommend new warnings be added to the labels of the epilepsy drugs. But the makers of these drugs want to avoid this. According to The Wall Street Journal, several companies at Monday's forum held by the Epilepsy Study Consortium expressed concern to the FDA that its analysis is flawed. Three firms, including Pfizer and Glaxo, made presentations at the meeting.

Pfizer, in particular, has good reason to want to prevent new warnings on the drugs. Pfizer is counting on one of the drugs on the FDA list, Lyrica, to be a huge growth driver for the company. Lyrica was recently approved to treat fibromyalgia in addition to epilepsy, and racked up $1.8 billion in sales last year. Pfizer is especially desperate to protect Lyrica, since its once-promising anti-smoking drug Chantix, got a suicide warning earlier this year.

Following Monday's meeting, some drug company executives told The Wall Street Journal that they expected the FDA would go ahead with new suicide warnings for epilepsy drugs, despite their protestations. Consumers will have to wait until at least July to see how this will all play out.

Dilantin Linked to Osteoporosis

Wed, 30 Apr 2008 00:00:00 -0700

A recent study revealed that the popular epilepsy drug Dilantin might be placing young women who take it for a year or more at higher risk for osteoporosis. The April 29 issue of Neurology states the bone loss described in the research was actually eight times higher than that experienced by pre-menopausal women not taking epilepsy drugs. "That suggests that if these women remain on this medication and have ongoing significant or accelerated bone loss that over time, they will be entering the peri-menopausal period with lower bone density and therefore a greater risk for low bone mineral density over time and therefore a higher risk of fractures," said study lead author Dr. Alison M. Pack, assistant professor of clinical neurology at Columbia University in New York City. Pack received funding from GlaxoSmithKline and other pharmaceutical companies for the study.

According to Dr. R. Eugene Ramsay, director of the International Center for Epilepsy at the University of Miami Miller School of Medicine, 90 percent of older people who have seizures are put on Dilantin, generally because of its low cost. "It's particularly important, because the older population has the highest incidence of epilepsy. There are more new-onset seizures occurring there and yet they are getting the cheapest and worst treatment," he said.

This study—partially supported by GlaxoSmithKline, which makes Lamictal—involved 93 pre-menopausal women from the ages of 18 to 40 with epilepsy. Each woman either took Dilantin (phenytoin), Tegretol (carbamazepine), Lamictal (lamotrigine), or Depokote (valproate). All women took 1,000 milligrams of calcium daily and were physically active. After one year, women taking Dilantin lost 2.6 percent of their bone density in the femoral neck of the hip while bone mineral density stayed about the same in the other three groups; bone mineral density stayed the same at the spine and the total hip. The speed—one year—at which Dilantin affected bone health was surprising, said Dr. Steven V. Pacia, director of the division of neurology at Lenox Hill Hospital in New York City.

Women who require epilepsy drugs can either switch to a medication other than Dilantin or they can increase their calcium intake, said Pack; however, according to Pacia, calcium supplementation may not be sufficient to offset Dilantin’s bone-depleting effects. "There may be a direct affect on bone absorption of calcium," Pacia said. "If the mechanism is damaged, the bone is not going to be able to take up calcium. An alternate drug that doesn't cause the same problem is preferable. In the rare cases we had to use Dilantin, drugs like Fosamax and Boniva can be used to try to counteract the effect, and that does happen."

Earlier research revealed an adverse effect on anti-epileptic drug treatment—including Dilantin and other drugs—on bone and mineral metabolism. And one previous study revealed anti-seizure medications had the same effect on the incidence of osteoporosis in older men as it did in older women, Ramsay said. "We're just beginning to recognize that we need to look at the long-term health care issues of anti-convulsants," Ramsay said.

Epilepsy Drug No Help Against Migraines

Tue, 12 Feb 2008 00:00:00 -0800

The epilepsy drug oxcarbazepine was strongly believed to have prevented migraine headaches; however, a new study suggests that this is not so. Epilepsy drugs such as oxcarbazepine have long been used for migraine prevention, according to Dr. Stephen Silberstein of the Jefferson Headache Center in Philadelphia and associates. Oxcarbazepine—marketed as Trileptal by Novartis or Trexapin by Taro—is used alone or in combination with other medications to treat certain types of seizures in people who have epilepsy and is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the brain and has also been used to treat bipolar disorder.

In a nearly five-month long study, investigators randomly assigned 170 men and women with a history of migraine to either a daily dose of oxcarbazepine or an inactive placebo. Both groups included patients who experienced between three and nine migraine attacks within a month. The results of the study showed that there was no difference between the group receiving a daily dose of oxcarbazepine and the group receiving a daily placebo dose in the change in the number of migraine attacks experienced from the beginning to the end of the study.

Likewise, the study revealed the severity of migraine attacks and the amount of acute rescue medication required for those attacks was not affected by treatment allocation of either the medication or the placebo. "The results of this trial do not support preliminary data which had suggested oxcarbazepine was effective in preventing migraine," Silberstein noted in a written pistatement. "While several epilepsy drugs have been used for decades to prevent migraine, oxcarbazepine did not prevent migraine in this study despite it being shown to be safe and well-tolerated."

Migraine is a debilitating headache that usually causes pulsing or throbbing pain in one area of the head. During migraines, people are very light and sound sensitive and may become nauseated and vomit. Migraine is three times more common in women than in men and some patients can tell when they are about to have a migraine because they see flashing lights or zigzag lines; temporarily lose their vision; or experience other sensory anomalies, such as smelling citrus. It is believed that there are a variety of triggers for migraine, including anxiety or stress, a lack of food or sleep, exposure to light, and hormonal changes (in women).

Silberstein also noted that the three epilepsy drugs that most effectively prevent migraine—topiramate, divalproex, and gabapentin—each have several mechanisms by which they treat migraine, including the ability to regulate a brain chemical known as GABA. In contrast, oxcarbazepine has no apparent activity on GABA. Silberstein says it is possible that epilepsy drugs must be able to regulate brain chemical in order to prevent migraine. GABA—or gamma-aminobutyric acid—is an inhibitory neurotransmitter found in the nervous system, that is, GABA helps the nerve impulses cross synapses and communicate with one another. Research has demonstrated GABA to be a very effective analgesic, eliminating pain from chronic conditions such as arthritis, lower back pain, and migraine.

Epilepsy Drugs Lawyers Double Suicide Risks Attroneys

Tue, 12 Feb 2008 00:00:00 -0800

Epilepsy Drugs Double Suicide Risks

On January 31, 2008, the Food & Drug Administration (FDA) warned that people taking epilepsy drugs were twice as likely to suffer from suicidal thoughts and behavior as those taking a placebo. Millions of people take epilepsy drugs. Such anti-seizure medications are used for a variety of illnesses in addition to epilepsy, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder that themselves carry a risk of suicide. The FDA said it would be working with manufacturers of marketed epilepsy drugs to include this new information about suicide risks in the labeling for these products

FDA Epilepsy Drug Suicide Study

The FDA began investigating if epilepsy drugs pose any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. Even though the FDA only looked at 11 epilepsy medications, the agency said the suicide warning applied to all epilepsy drugs. The FDA epilepsy drug analysis included the following drugs

Carbamazepine(marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. According to the FDA for every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

Legal Help

If you or a loved one suffered from thoughts and/or behavior while taking epilepsy drugs, you may have valuable legal rights. Please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.