Perampanel decreased median seizure frequency and improved responder rates.

Eisai reported positive results of a Phase III study with perampanel (E2007) for the treatment of partial seizures in patients with epilepsy. The compound is a highly selective noncompetitive AMPA-type glutamate receptor antagonist.

The double-blind, placebo-controlled, parallel-group study (study 306) showed that perampanel was effective in reducing median seizure frequency and increasing responder rates, the primary outcome measures in the U.S. and EU, respectively. The findings were statistically significant in 4 mg and 8 mg doses compared to placebo. A linear trend for dose response was also statistically significant.

The global study consisted of 706 patients from 25 countries who were randomized to placebo or one of three perampanel doses. Patients started on 2 mg doses of perampanel, then remained on 2 mg or increased dosage weekly in 2 mg increments to their randomized doses of 4 mg or 8 mg. The drug was well tolerated, and the most common adverse events reported were dizziness, somnolence, and headache.

Study 306 is the first trial in Eisai’s Phase III development program for perampanel. Two more global Phase III studies are under way, and results are expected to be available within one year. Eisai intends to simultaneously submit in the U.S. and EU in the fiscal year 2011, which for the firm is the year ending March 31, 2012.

Source: GEN

Popularity: 1% [?]

We’ve written before how a hard conk on the head may seem like an isolated event, but can lead to cognitive, health and other problems years down the line. Now two researchers are proposing traumatic brain injury be redefined, managed and reimbursed by insurers as a chronic disease to better monitor and, if possible, address those possible after-effects.

In a review of scientific literature published in the Journal of Neurotrauma, the authors, both from the University of Texas Medical Branch at Galveston, say that brain trauma can kick off a disease process associated with a higher risk of epilepsy, sleep apnea, neuroendocrine disorders, psychiatric problems, non-neurological disorders such as sexual dysfunction and neurodegenerative disorders such as Parkinson’s and Alzheimer’s dementia, among other conditions. (The WSJ wrote recently about research suggesting that repeated blows to the head in sports are associated with a condition similar to ALS, or Lou Gehrig’s disease.)

TBI is also linked to a reduced life expectancy, they write. Because of all these associated problems, it deserves to be classified as “the beginning of an ongoing, perhaps lifelong process, that impacts multiple organ systems and may be disease causative and accelerative,” they write.

If it were, patients would be monitored and tracked for possible problems, much as diabetics are now, and if necessary directed into rehab, says Brent Masel, one of the paper’s authors, a clinical associate professor at UTMB’s neurology department and president and director of the Transitional Learning Center, which offers brain injury rehab. Health-care providers could be taught to be on the lookout for injury-related conditions that can present years down the road, such as epileptic seizures. Insurers could reimburse for rehab more often, if problems were associated with the injury.

And researchers (including themselves, it should be noted) might get more funding to study treatments for use months or years down after the initial injury, they write.

Masel says it’s not known how many people with TBI — which can be anything from a hit on the head that results in distorted consciousness or a temporary lack of awareness to a comatose state — go on to have problems. Obviously, the more severe the injury, the higher the risk of other issues. But there’s now an awareness that even, say, athletes who “have a mild injury, say, are bonked on the head and then go back to play football” might face cognitive or other problems going forward. Now, he says, “we’re following them — we’re going to know,” eventually, what the risk is, he says.

He and his co-author, Douglas DeWitt, a professor in the department of anesthesiology at UTMB, write that they’re not trying to scare or discourage people with TBI, but to raise awareness of the problems that can affect some — but not all– patients.

Source: The Wall Street Journal

Popularity: 2% [?]

Did the FDA speak too soon when it slapped a suicide warning on a class of epilepsy drugs? New research suggests so. A study of 5 million patients, published in the New England Journal of Medicine, now has found that the suicide risk is linked not to the drugs, but to the disorders the drugs are prescribed to address. Added to recent research that linked some of the epilepsy drugs in question with suicide risk–but not others–the data has at least one expert saying the FDA should pull the warning.

The FDA added the warning after reviewing data from 199 studies that suggested that patients using these drugs did have a higher risk of suicidal behavior than other patients did. But the FDA study didn’t cover nearly as many patients, and while the agency research had 24 weeks follow-up, the new study followed patients for six years, HealthDay reports.

“The warning on AEDs and suicide was never justified, and this data strongly argues for its removal,” says Dr. Orrin Devinsky, director of the New York University Comprehensive Epilepsy Center, as quoted by HealthDay.

There are two subgroups of patients that did show an increased suicide risk in the new study: Those with depression and those who weren’t using the epilepsy drugs for epilepsy, depression or bipolar disorder. The reason for the former risk could be attributed to depression itself, the study authors said; it may be that only patients with severe depression are given these meds rather than antidepressants. The latter? The researchers aren’t sure.

Among the drugs studied were Pfizer’s Neurontin (gabapentin), GlaxoSmithKline’s Lamictal (lamotrigine), UCB’s Keppra (levetiracetam), and Novartis’ Trileptal (oxcarbazepine). The FDA has not responded yet.

Source: FiercePharma

Popularity: 3% [?]

Some seizure drugs may not raise the risk of suicide for patients with epilepsy as feared, but they more than double the risk for people with depression, researchers reported on Wednesday.

They found evidence that the drugs do not make it more likely that patients with epilepsy will commit suicide. But patients take the drugs for a range of other conditions and some of these had a 65 percent higher risk.

In 2008 the U.S. Food and Drug Administration warned that epilepsy drugs may increase the risk of suicide.

The new study, led by Dr. Alejandro Arana of Risk MR Pharmacovigilance Services in Zaragoza, Spain, culled records from 5 million patients in Britain treated from July 1988 through March 2008. They included 8,212 suicide attempts.

“Our findings suggest that treatment with antiepileptic drugs does not confer an additional risk of suicide-related events among patients with epilepsy,” they wrote in the New England Journal of Medicine.

The drugs tested include topiramate, sold by Johnson & Johnson under the Topamax brand, and also included as part of Vivus’s experimental obesity drug Qnexa.

They include Cephalon’s Gabitril, known generally as tiagabine, UCB Pharmaceuticals’ Keppra or levetiracetam, H. Lundbeck’s Sabril or vigabatrin, Pfizer’s Neurontin or gabapentin and Lyrica or pregabalin, GlaxoSmithKline’s Lamictal or lamotrigine, Novartis’ Trileptal or oxcarbazepine and Eisai’s Zonegran or zonisamide.

They also included valproate, sold by Abbott Laboratories as Depakine and Sanofi-Aventis as Epilim, and carbamazepine, sold as Carbatrol by Shire and Tegretol by Novartis.

The researchers found that people with epilepsy, depression or the abrupt mood swings of bipolar disorder who were not taking epilepsy drugs had a higher likelihood of suicide attempts in the first place.

But taking one of the seizure drugs did not increase the risk of suicide-related events for people with epilepsy or bipolar disorder, or among patients whose epilepsy was combined with depression.

“In general, our results do not confirm the findings previously reported by the FDA,” the Arana team concluded.

Last week a separate group of researchers, who also studied British patients, concluded that attempted suicide or self-harm only occurred in epilepsy patients taking newer drugs that have been linked to a risk of depression.

That study, in the journal Neurology, tracked 453 suicide attempts or incidents of self-harm, a small fraction of the number in the Arana survey.

Source: Reuters

Popularity: 4% [?]

While all epilepsy drugs carry a warning about an increased risk of suicidal behavior, it may only be certain newer medications that are connected to the hazard, a study published Monday suggests.

In a study of 44,300 UK patients who used epilepsy drugs between 1990 and 2005, researchers found an increased risk of suicide, attempted suicide or “self-harm” only among current users of certain newer medications that have previously been linked to a risk of depression.

Those drugs include topiramate (Topamax), tiagabine (Gabitril), levetiracetam (Keppra) and vigabatrin (Sabril).

The findings, published in the journal Neurology, add to a debate about the Food and Drug Administration’s decision, in 2008, to require all epilepsy medications to carry a warning about the risk of suicidal behavior.

The move arose from the findings of an FDA “meta-analysis” of 199 clinical trials testing 11 different epilepsy medications. That analysis, which combined the results of all the trials, found that patients receiving medication had a higher rate of suicidal thoughts and behavior during the study periods than those given a placebo — 0.4 percent, versus 0.2 percent.

The analysis was not, however, able to distinguish whether the risk was associated with any particular drugs. And critics argued that requiring all epilepsy medications to carry a suicide warning was too broad a measure, as the drugs are not all alike.

These latest findings offer some support for that contention. But they do not mean that the drugs implicated in this study are the only ones connected to suicide risk, according to the researchers and others who reviewed the study.

For one, the findings are based on a review of information from a database — a study design that cannot prove cause-and-effect.

Moreover, there were only a small number of documented suicides, suicide attempts or instances of self-harm (self-inflicted injuries without a clear intent of suicide), according to Dr. Frank Andersohn and his colleagues at Charite-University Medical Center in Berlin.

The researchers found 453 cases among all 44,300 patients, based on a UK database of electronic medical records.

They then attempted to look at the risk of suicidal behavior and self-harm according to different categories of epilepsy drug. Topiramate, tiagabine, levetiracetam and vigabatrin were grouped together as newer drugs with a “high” risk of depression — based on the fact that in clinical trials, more than 1 percent of patients using the drugs developed depression.

Another group included four newer medications considered to have a low depression risk: gabapentin (Neurontin), lamotrigine (Lamictal), oxcarbazepine (Trileptal) and pregabalin (Lyrica). The other two groups were barbiturates and older epilepsy drugs like valproate (Depakine, Epilim) and carbamazepine (Carbatrol, Tegretol).

Overall, the researchers found a three-fold higher risk of suicidal behavior or self-harm among current users of the group including topiramate, tiagabine, levetiracetam and vigabatrin, as compared with patients who had not used any epilepsy medication in the past year.

However, the numbers, again, were small.

There were only two cases each among current users of topiramate, levetiracetam and vigabatrin, and none among tiagabine users.

The findings, therefore, need to be “interpreted with caution” and confirmed in future studies, Andersohn and his colleagues write.

The results also differ from those of a study published in April in the Journal of the American Medical Association. In that study, researchers found that new users of gabapentin, lamotrigine, oxcarbazepine and tiagabine had a higher suicide risk than those on topiramate — one of the drugs linked to an increased risk in this latest study.

An editorial published with the study agrees that the research is a “good initial attempt” at looking at a complicated question, but more work is needed.

Epilepsy itself is linked to a higher-than-average risk of depression and suicide, pointed out Dr. Josemir W. Sander of the University College London in the UK, one of the editorial authors. That, he told Reuters Health in an email, can make it hard to “disentangle” the potential effects of epilepsy medications themselves.

“The fact that each study into this issue seems to come up with different answers just confirms my belief that this does not have an easy answer,” Sander said.

A limitation of the current study is that it lacked detailed descriptions of patients’ epilepsy type and any co-existing psychiatric disorders, according to Sander.

There is “no doubt,” he explained, that there are many different subgroups of people with epilepsy, and certain patients are more vulnerable to any increased risk of suicidal behavior linked to medications.

For now, Sander said, it is important for people with epilepsy to have a psychiatric evaluation before starting a new drug — a step the FDA has advised doctors to take.

Indeed, the key message for people with epilepsy is that the most important factor in their risk of suicidal thoughts or behavior is whether they have a history, or a family history, of depression or anxiety, according to Dr. Andres Kanner, a professor of neurological sciences at Rush Medical College in Chicago, and chair of the American Epilepsy Society’s task force on the psychiatric aspects of epilepsy.

Certain epilepsy medications may facilitate the development of suicidal thoughts and behavior in vulnerable people, Kanner told Reuters Health, but any risk linked to a drug itself would be small.

“Make sure your doctor knows if you have a history of depression or anxiety,” Kanner advised, noting that that includes a personal or family history. The doctor can then consider that in the overall management of a patient’s epilepsy.

Going forward, Sander said there remains an “urgent” need for clinical trials looking at individual epilepsy drugs in different subgroups of patients, to get a clearer picture of each medication’s full risk “profile.”

The study was funded by drugmaker Bayer Schering Pharma, and two co-authors on the work have served as consultants for Novartis and Sanofi-Aventis — makers of two of the medications not linked to suicide risk in this study.

Sander and his co-author on the editorial have ties to several makers of epilepsy drugs — including ones that were and were not linked to suicide risk in this study. The companies include UCB (maker of Keppra), Pfizer (Neurontin) and GlaxoSmithKline (Lamictal).

Kanner has also received research support from various companies that make epilepsy drugs.

Source: Reuters

Popularity: 4% [?]

British scientists believe they have found specific patterns of brain activity in children and young people which could be signs or “markers” of those who will later go on to develop mental illnesses such as schizophrenia.

Researchers from Nottingham University, who presented their study at the Forum for European Neuroscience in Amsterdam, said the patterns suggest it may be possible in future to identify those at risk of becoming ill before they develop symptoms.

“If we can identify people who are at particularly high risk of developing schizophrenia, perhaps using neurocognitive brain markers, then we might be able to reduce that risk and also help them to function better,” said Dr Maddie Groom, who worked on the study and gave a briefing to reporters in London.

“If we give them a better start, they may encounter the illness in a more positive way and not get quite so ill.”

Hundreds of millions of people worldwide are affected by mental, behavioral and neurological illnesses such as schizophrenia, attention deficit hyperactivity disorder (ADHD), depression, epilepsy and dementia.

Many people who go on to develop diverse mental health problems will have a history of behavioral problems going back to childhood, but experts say the problem with finding them at that stage is that differences then are often extremely subtle.

In one study, Groom and her colleagues investigated looked at the healthy siblings of people with schizophrenia, who also have a very slightly increased risk of developing schizophrenia compared with the general population.

Using brain imaging to read activity levels, the scientists asked the siblings to perform task which involved playing an alien-zapping computer game in which they needed to respond quickly, and crucially, halt the urge to respond if the wrong kind of alien popped up. The task was called a “go, no-go” task.

“When we measured the brain activity of the siblings of people with schizophrenia, their brain activity was reduced at the time when they needed to pay attention to the stimulus, and when they needed to inhibit their response,” Groom explained.

She said this suggested the subtle differences in brain activity may act as a risk marker for the disorder.

In a second study, scientists compared brain activity of children with ADHD — a mental disorder that affects between 8 and 12 percent of children, and 4 percent of adults worldwide.

The researchers used the same “go, no-go” task in various scenarios, including when the children were taking their medication, Ritalin, and when they were not, and then using an additional system of rewards and penalties.

Millions of people take ADHD drugs including Novartis Ritalin, which is known generically as methylphenidate, and Shire Plc’s Adderall and Vyvanse. In the United States alone, 2008 sales for these drugs was about $4.8 billion, according to data from IMS Health.

Groom’s results showed that children who were taking medication, and children given an incentive, performed better than those who had neither medicines nor incentives.

This suggests, Groom said, that doctors may be able to find new ways to treat children with ADHD using a combination of behavioral strategies and drugs.

Source: Reuters

Popularity: 5% [?]

Last fall, when Dainippon Sumitomo Pharma announced that it had inked a deal to buy Sepracor for $2.6 billion, the Japanese pharma company cited the once-daily epilepsy drug Stedesa as one of the near-term drug prospects it was most excited about. Yesterday afternoon, though, the FDA declined to approve Stedesa, and now Dainippon is attempting to sort out what steps it will have to take next.

Dainippon didn’t spell out exactly what the FDA discussed in its complete response letter. And a spokesperson didn’t add much when contacted by Bloomberg.

“Sepracor will meet with the FDA to discuss and better understand the complete response letter and the agency’s expectations,” wrote spokesperson Susan Adler in an e-mail. “This will include whether there is a need to conduct any new studies on Stedesa.”

“While we are disappointed by this decision, we are committed to working closely with the FDA to gain approval of Stedesa, which we continue to believe has significant potential to address the continuing unmet need in the treatment of patients with epilepsy,” says Saburo Hamanaka, the CEO of the Marlborough, MA-based Sepracor, in a statement. Stedesa was studied in three Phase III trials which involved more than 1,000 patients from 23 countries.

Source: FierceBiotech

Popularity: 2% [?]

Researchers have shed new light on the mechanism behind epilepsy attacks in the brain, revealing a potential new target for drug treatment.

Around half a million people in the UK have some form of epilepsy.

Until recently the focus of research has been on cells called neurons, but a US study points to a completely different cell.

Nature Neuroscience journal reports its behaviour may be key to uncontrolled brain activity behind the condition.

Epilepsy attacks, which can manifest as fits in some people, or “absences” in others, are caused by too much electrical signalling from the brain’s neurons.

However, in many cases, the reason for this over-activity is poorly understood.

Scientists now believe that, in some cases, although the problem happens at the neuron the underlying reason may be the failure of surrounding cells to help control this activity.

The latest study, from the Tuft University School of Medicine and the Children’s Hospital of Philadelphia, provides the strongest evidence yet that a cell called an astrocyte is the culprit.

The astrocyte is known to have a wide range of functions, including supplying nutrients to other brain cells, and even helping the brain cope with damaged nerve cells.

In some brain diseases, the astrocytes swell up and behave differently, and it is this condition which the researchers believe is linked to epilepsy.

No inhibition

They induced this swelling in brain samples from mice, then tested whether this made a difference to the ability of the brain cells to “turn down”, or inhibit, the brain signals from specific neurons.

They found that the enlarged astrocytes led to reduced levels of a brain chemical known to inhibit electrical signalling from the neurons.

Dr Douglas Coulter, one of the researchers, said: “We already know that inhibition is a powerful force in the brain.

“In epilepsy, inhibition is not working properly, and uncontrolled signalling leads to epileptic seizures.

“By better understanding the detailed events that occur in epilepsy, we are gaining knowledge that could ultimately lead to better treatments for epilepsy, and possibly for other neurological diseases.”

Professor Vincenzo Crunelli, a neuroscientist from the University of Cardiff, said other research, including his own, now pointed towards a role for astrocytes in various different types of epilepsy.

He said the finding might be particularly relevant in a form of epilepsy called temporal lobe epilepsy, which can be resistant to treatment.

He said: “This certainly suggests that the astrocytes may be involved in maintaining this over-excitation of the neurons.

“If this is the case, it offers the chance of a new therapeutic target.”

Source: BBC NEWS

Popularity: 5% [?]

Pfizer lost its bid to escape a multimillion-dollar racketeering verdict when a federal jury ruled that the drugmaker’s marketing of the epilepsy drug Neurontin violated federal and state law. Now, Pfizer faces damages of up to $142 million in the case.

Kaiser Foundation’s health plan and hospitals had sued the drugmaker, claiming that it had spent more money than necessary on Neurontin because of Pfizer’s marketing of the drug for off-label uses. Not only did the drugmaker push the drug for those unapproved indications, but Pfizer knew the drug didn’t work for those uses, either, Kaiser claimed.

Kaiser calculated that it had overpaid for Neurontin on five unapproved uses–to the tune of about $90 million. The jury, however, set damages at just over half of that: $47 million. Under the racketeering law, those damages are automatically tripled; hence the $142 million total. ”We hope this decision will send a message to the medical community and pharmaceutical industry that manufacturers must adhere to high ethical and legal standards in their research and marketing of drugs,” Kaiser says in a statement.

Pfizer says it disagrees with the ruling–and will fight it. “We are disappointed with the verdict and will pursue post-trial motions and an appeal,” spokesman Christopher Loder says in a statement (as quoted by Dow Jones). “The verdict and the judge’s rulings are not consistent with the facts and the law.”

Source: FiercePharma

Popularity: 2% [?]

Deep brain stimulation is a promising therapy for epilepsy, US researchers from Stanford University have said.

In a clinical trial, 110 people had electrodes implanted in their brains and their seizures were monitored.

Forty-one per cent of patients showed a reduction in seizures after 13 months while 56% experienced a reduction after two years.

The patients all suffered from regular epileptic seizures and had failed to respond to drug treatment.

Deep brain stimulation (DBS) is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain.

In the group of patients who received brain stimulation, researchers noted a 41% reduction in seizures compared to a 14.5% decline in seizures in a control group. This group did not receive stimulation.

Invasive therapy

Epilepsy is a common neurological disorder which is characterised by recurrent seizures. These seizures can cause temporary loss of consciousness, convulsions, confusion or disturbances in sensations.

According to the World Health Organization, epilepsy affects 50 million people worldwide.

Previous studies indicate that one third of those with epilepsy do not respond to anti-epileptic drugs.

Dr Robert Fisher, director of the Epilepsy Centre at Stanford University and lead author of the study, said electrical deep brain stimulation does reduce seizure frequency in patients.

But he cautioned: “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.”

Simon Wigglesworth, deputy chief executive at UK charity Epilepsy Action, said: “We have been hopeful for some time that deep brain stimulation may be a treatment option for some people with epilepsy.

“This study is exciting news and could be an important development in the treatment of epilepsy in the 30% of people whose seizures don’t respond to traditional drug therapies.”

The research is published online in the journal Epilepsia.

Source: BBC NEWS

Popularity: 5% [?]