20080206

Serious Health Risks with Antiepileptic Drugs

FDA warns about possible risk of suicidal thoughts and behavior in patients taking antiepileptic drugs

FDA issued new information on Jan. 31, 2008, to alert health care professionals about an increased risk of suicidal thoughts and behaviors in patients who take medications called antiepileptics. Such drugs treat epilepsy, bipolar disorder, migraine headaches, and other conditions.

FDA studied suicidality reports from 11 antiepileptic drug studies and found that patients taking antiepileptics have about twice the risk of suicidal thoughts and behaviors, compared with patients receiving an inactive substance (placebo). This risk corresponds to an estimated 2.1 per 1,000 more patients in the drug treatment groups who experienced suicidality than in the placebo groups.

FDA recommends that

* Patients currently taking antiepileptic medicines not make any changes without first talking to their health care providers.
* Health care providers notify patients, their families, and caregivers of the potential for an increase in the risk of suicidality, so that patients can be closely observed for notable behavior changes.

Although only the following drugs were part of the analysis, FDA expects that all medications in the antiepileptic class share the increased risk of suicidality:

* 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 agency will work with manufacturers of marketed antiepileptic drugs to include this new information in the labeling of these products. FDA anticipates that labeling changes will be applied broadly to the entire class of drugs.

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:
o Talking or thinking about wanting to hurt yourself or end your life
o Withdrawing from friends and family
o Becoming depressed or having your depression get worse
o Becoming preoccupied with death and dying
o Giving away prized possessions

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

The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies.

Copyright Information: Public domain information with acknowledgement given to the U.S. National Library of Medicine.

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