Epilepsy advocates propose strategies to heighten treatment expectations

Survey reveals room for improvement in balancing seizure control and side effects

WASHINGTON (March 28, 2008) — On the heels of the nation’s largest event dedicated to the epilepsy community, the National Walk for Epilepsy, advocates today announced their recommendations in response to a new national survey uncovering key challenges facing the epilepsy community. Challenges include gaps in patient-physician communication around medication-related side effects and low public awareness of epilepsy.

According to the survey, sponsored by ORTHO-McNEIL NEUROLOGICS®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, 75 percent of epilepsy patients experience medication-related side effects and for the majority, these impact their daily lives, including 57 percent who say work or school are affected. A disconnect exists between patients and healthcare professionals surrounding their discussions on these side effects. While 98 percent of physicians report discussing medication-related side effects with patients, less than half (47 percent) of epilepsy patients report these discussions take place. And, more than one-quarter of patients report they sometimes feel reluctant to broach this topic during office visits. Not surprisingly, healthcare professionals underestimate the number of patients experiencing medication-related side effects, estimating this figure at just 43 percent. The most common side effects according to the survey are fatigue, poor memory, weight gain or weight loss and loss of concentration.

“These findings suggest treatment expectations among epilepsy patients are simply too low. According to the survey, 61 percent of people with epilepsy believe that side effects are just something they have to live with,” said roundtable moderator and Epilepsy Foundation CEO and President Eric Hargis. “People with epilepsy should be proactive in discussing their treatment plans, opening up about the side effects they experience and sharing how these side effects are affecting their lives.”

Panelists at the nine-person roundtable included some of the nation's premiere epileptologists, patients and caregivers and celebrity advocates, including Greg Grunberg, star of NBC’s television series "Heroes" and father of a son with epilepsy, and New York Giants defensive back Geoffrey Pope whose grandmother has epilepsy.

Improving Treatment Plans

Roundtable participants agreed that people with epilepsy and healthcare professionals should work together to ensure treatment plans are tailored to the individual. According to the survey, 85 percent of patients would prefer to have a more active role in making their treatment decisions.

“It is crucial for patients to speak up and be a part of developing their treatment model,” said Georgia Montouris, M.D., director of epilepsy services at the Boston University School of Medicine and Boston Medical Center.

Healthcare professionals surveyed say they would recommend an alternative treatment plan at least half the time for those patients experiencing medication-related side effects. "We need to increase the focus on individualizing treatment plans and strive for optimal balance between seizure control and minimization of side effects so that we can improve the overall well-being of people with epilepsy,” added Dr. Montouris.

Roundtable participant Caitlin Purcell, 17, explained how her healthcare professional started her on one medication, but when she was still experiencing seizures he added new medications to her regime to help her further manage her condition. Physicians often try a variety of therapy mixes to customize the treatment approach, “and Caitlin’s physician was trying to find the right ‘cocktail’ for her,” noted Dr. Mark Spitz, head of the Adult Comprehensive Epilepsy Program at the University of Colorado.

Participants also discussed the need for new treatments. “We need to continue funding research and development as there is a need for drugs that help us better straddle this balance until a cure for epilepsy can be found," said Hargis.

Other recommendations for improving communication and treatment plans included:

• Patients and caregivers should advocate for themselves and discuss their treatment plans, side effects and what other steps can be taken with their healthcare professionals. “As long as there is seizure activity, there are still things that can be done or treatments that can be tried,” said Grunberg.
• Patients should strive for a more individualized treatment plan by sharing a daily diary or record of how they are feeling, any medication side-effects or breakthrough seizures they experience with their healthcare professional.
• Patients and caregivers, as well as healthcare professionals, should raise their standards and not settle if the patient is still experiencing seizures or side effects. “It’s not a trade-off. We may not be able to get every patient to the point of experiencing no seizures and no side effects, but we should never stop trying,” said Dr. Montouris.
• Finally, panelists encouraged patients to not hesitate to seek a second opinion when patients are not achieving their treatment goals.

Raising Public Awareness of Epilepsy

According to the survey, three-quarters of people with epilepsy and 90 percent of physicians feel that the general public is not well-informed about epilepsy. Roundtable participants agreed that this is a major cause for the stigma surrounding epilepsy and some shared their stories of how this has impacted their lives.

“The other kids (in school) are sometimes afraid of me. And sometimes even if they want to have me over after school, their parents are afraid, especially if they haven’t seen me have a seizure,” explained 14-year-old panelist Carly Richards of Chicago.

Participants addressed the need for continued public education programs that focus on eliminating stigma associated with epilepsy, such as the March 29th annual National Walk for Epilepsy. The panelists encouraged all people who have epilepsy or know someone with the condition to speak out and share their experiences.

“We are at a tipping point for bringing epilepsy out in the open,” said Grunberg. “We need to continue the dialogue we started here today to increase awareness and break down the stigma that is unfairly associated with this disorder.”

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The roundtable, which took place in Washington, D.C. on Friday, March 28, was hosted by the Epilepsy Foundation and ORTHO-McNEIL NEUROLOGICS®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Please visit: www.epilepsyfoundation.org to find more information about upcoming 2008 initiatives resulting from the roundtable discussion.

About the Survey

Richard Day Research fielded a survey to epilepsy patients and healthcare professionals. Data from both audiences were collected in January 2008. Healthcare professional data included 459 healthcare professionals—comprised of 155 primary care physicians (family, general, or internal medicine) and 304 neurologists. Patient data included 414 people diagnosed with epilepsy, screened for having seen a healthcare professional for epilepsy within the last two years.

About the Epilepsy Foundation

The Epilepsy Foundation, a national nonprofit with affiliated organizations throughout the United States, has led the fight against epilepsy since 1968. The Foundation’s goals are to ensure that people with seizures are able to participate in all life experiences; and prevent, control and cure epilepsy through services, education, advocacy and research, so not another moment is lost to seizures. For additional information, please visit www.epilepsyfoundation.org.

About ORTHO-McNEIL NEUROLOGICS

Headquartered in Titusville, N.J., ORTHO-McNEIL NEUROLOGICS focuses exclusively on providing solutions that improve neurological health. The company currently markets products for Alzheimer's disease, epilepsy and acute and preventive migraine treatment. ORTHO-McNEIL NEUROLOGICS, in conjunction with internal and external research partners, continues to explore new opportunities to develop solutions for unmet healthcare needs in neurology.

original http://www.eurekalert.org/pub_releases/2008-03/gi-eap032808.php

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I wish to comment on some of the points here but for now have just posted the news item as sometimes can be difficult to track later.

Suicide Risk From 11 Epilepsy Drugs

FDA ALERT [1/31/2008]: The FDA has analyzed reports of suicidality (suicidal behavior or ideation) from placebo-controlled clinical studies of eleven drugs used to treat epilepsy as well as psychiatric disorders, and other conditions. These drugs are commonly referred to as antiepileptic drugs (see the list below). In the FDA’s analysis, patients receiving antiepileptic drugs had approximately twice the risk of suicidal behavior or ideation (0.43%) compared to patients receiving placebo (0.22%). The increased risk of suicidal behavior and suicidal ideation was observed as early as one week after starting the antiepileptic drug and continued through 24 weeks. The results were generally consistent among the eleven drugs. Patients who were treated for epilepsy, psychiatric disorders, and other conditions were all at increased risk for suicidality when compared to placebo, and there did not appear to be a specific demographic subgroup of patients to which the increased risk could be attributed. The relative risk for suicidality was higher in the patients with epilepsy compared to patients who were given one of the drugs in the class for psychiatric or other conditions.

All patients who are currently taking or starting on any antiepileptic drug should be closely monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug products and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA intends to update this document when additional information or analyses become available.

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Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program; see addresses below.

Considerations for Physicians and Other Health Care Professionals

Data from 199 placebo-controlled clinical studies covering eleven different antiepileptic drugs were reviewed and analyzed for reports of suicidal behavior (completed suicides, suicide attempts and preparatory acts) and suicidal ideation. The studies examined the effectiveness of the drugs in epilepsy, psychiatric disorders (e.g., bipolar disorder, depression and anxiety) and other conditions (e.g., migraine and neuropathic pain syndromes). The analysis included a total of 43,892 patients ages five and older (27,863 in drug treatment groups and 16,029 in placebo groups).

There was a statistically significant increased risk of suicidal behavior and suicidal ideation in the patients randomized to receive an antiepileptic drug compared to patients who received a placebo. The estimated overall risk was about twice that of the placebo group. There were an estimated 2.1 per 1000 (95% CI: 0.7, 4.2) more patients in the drug treatment groups who experienced suicidal behavior or ideation than in the placebo groups.

Four of the patients who were taking one of the antiepileptic drugs committed suicide, whereas none of the patients in the placebo group did. The increased risk of suicidal behavior and suicidal ideation was observed at one week after starting the drug and continued to at least 24 weeks. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be reliably assessed.

FDA will be working with manufacturers of marketed antiepileptic drugs to include this new information in the labeling for these products. FDA is also planning to discuss these data at an upcoming advisory committee meeting.

All patients treated with antiepileptic drugs should be monitored for suicidality and other unusual changes in behavior. Symptoms such as anxiety, agitation, hostility, mania and hypomania may be precursors to emerging suicidality.

Healthcare professionals who prescribe antiepileptic drugs should:

• Balance the risk for suicidality with the clinical need for the drug


• Be aware of the possibility of the emergence or worsening of depression, suicidality, or any unusual changes in behavior;


• Inform patients, their families, and caregivers of the potential for an increase in the risk of suicidality so they are aware and able to notify their healthcare provider of any unusual behavioral changes.

Information for patients, family members, and caregivers:

• Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;


• Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;


• Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.


• Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:





• Talking or thinking about wanting to hurt yourself or end your life


• Withdrawing from friends and family


• Becoming depressed or having your depression get worse


• Becoming preoccupied with death and dying


• Giving away prized possessions

If these or any new and worrisome behaviors occur, contact the responsible healthcare professional immediately.

Background and Data Summary

After preliminary analyses of data from several drugs in this class suggested an increased risk of suicidality, in March 2005, FDA requested data from manufacturers of marketed antiepileptic drugs for which there were adequately designed controlled clinical trials in order to review the possible association between these drugs and suicidality events. In an effort to obtain the most complete and accurate data for this review, requests for additional information and clarification were sent to the manufacturers in 2006 and 2007. The analyses performed were similar to those performed by FDA for antidepressant drugs in the last several years.

One-hundred ninety nine placebo-controlled clinical studies covering eleven different drugs were included in the primary analysis. The conditions studied in these clinical trials included epilepsy, selected psychiatric illnesses, and other indications, including migraine and neuropathic pain syndromes. The analysis included 27,863 patients in drug treatment groups and 16,029 patients in placebo groups. Patients included in the analysis were five years of age or older. The individual sponsors of the drugs were responsible for identifying suicidal behavior and suicidal ideation events in their databases based on the instructions provided by FDA.

There were 4 completed suicides among patients in drug treatment groups and none among the patients in placebo groups. Overall, 0.43% of the patients in drug treatment groups experienced suicidal behavior or ideation versus 0.22% of the patients in placebo groups, corresponding to an estimated 2.1 per 1000 (95% CI: 0.7, 4.2) more patients in the drug treatment groups who experienced suicidal behavior or ideation than in the placebo treatment groups (See Table). In this analysis, the relative risk for suicidal thoughts or behavior was higher for patients with epilepsy compared to those patients with psychiatric or other disorders (See Table). The higher risk for suicidal behavior or suicidal ideation was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among the drugs and were seen in all demographic subgroups. Specifically, there was no clear pattern of risk across age groups.

Relative Risk and Risk Difference for Suicidality According to Trial Indication

Indication	Placebo Patients with Events Per 1000 Patients	Drug Patients with Events Per 1000 Patients	Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients	Risk Difference: Additional Drug Patients with Events Per 1000 Patients
Epilepsy	1.0	3.5	3.6	2.5
Psychiatric	5.2	8.3	1.6	3.1
Other	0.8	2.0	2.3	1.1
Total	2.2	4.3	2.0	2.1

The following is a list of antiepileptic drugs* included in the analyses:

• Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)


• Felbamate (marketed as Felbatol)


• Gabapentin (marketed as Neurontin)


• Lamotrigine (marketed as Lamictal)



• Levetiracetam (marketed as Keppra)
  
  
  
  • Patient Information Sheet
  
  
  
  


• 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)

* Some of these drugs are also available in generic form.

Although the drugs listed above were the ones included in the analysis, FDA expects that the increased risk of suicidality is shared by all AEDs and anticipates that the class labeling changes will be applied broadly.

Adverse reactions or quality problems experienced with the use of this Product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Online: www.fda.gov/medwatch/report.htm


• Regular Mail: use postage-paid FDA form 3500 available at: www.fda.gov/MedWatch/getforms.htm.


• Mail to MedWatch 5600 Fishers Lane, Rockville, MD 20852-9787



• Fax: 1-800-FDA-0178