Epilepsy Talk

Death, depression and AEDs | June 25, 2023

“Suicide Risk from 11 Anti-Epilepsy Drugs,” headlines blared across the country.

But we’re still here.

Was it sensationalism by the journalists, irresponsibility by the pharmaceutical industry or laxness of the FDA?

The answer is none of the above.   And, by the way, they forgot to include anti-depressants.

At best, I’d call it a misunderstanding.  At worst, I’d call it manipulation.

Meanwhile those taking these eleven drugs were fearful.  And rightfully so.  Should they throw out their anti-depressants?  Ditch their AEDs?  Imagine what the statistics would have been then!

FDA analysis of nearly 200 studies showed that patients taking 11 specific anti-seizure drugs were twice as likely to have suicidal tendencies as those not taking the drugs.  Yet those drugs used to control seizures also help control the symptoms of some psychiatric disorders.

And they noted that the overall risk remained small.

“All patients who are currently taking or starting on any anti-epileptic drug should be closely monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression,” the FDA warned in a letter to health professionals.

In the clinical trials, patients receiving inactive placebo pills had a 0.22% incidence of suicidal tendencies.  Those receiving the epilepsy drugs had a 0.43% incidence of suicide ideation — twice that of placebo recipients, but still a very small risk.

The 11 drugs cited by the FDA (based upon clinical analysis) were:

Carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR)

Divalproex sodium (Depakote, Depakote ER)

Felbamate (Felbatol)

Gabapentin (Neurontin)

Lamotrigine (Lamictal)

Levetiracetam (Keppra)

Oxcarbazepine (Trileptal)

Pregabalin (Lyrica)

Tiagabine (Gabitril)

Topiramate (Topamax)

Zonisamide (Zonegran)

* Plus the generic versions of these drugs.

Yet, in truth, the clinical trials showed the relative risk per 1000 patients to be:

Epilepsy 3.53

Psychiatric 1.51

Other 1.87

But here’s the glitch: some people with epilepsy may be clinically depressed, so it’s hard to tell whether it’s the medication or the condition that is causing the suicidal behavior.

One study stated that 80% of the patients with epilepsy were also diagnosed as having a depressive disorder. Upwards of 60% of these individuals had a history of significant episodes of depression.  And 10-32% experienced symptoms of anxiety.

And they forgot to mention AEDs positive effect on bipolar disorder, migraines and other conditions, too.

So, literally taken, you could say the message was seize and die.

Not acceptable alternatives.

Representatives from the American Academy of Neurology stressed that epilepsy patients are already prone to depression and suicidal behavior, making it difficult to gauge the negative impact of the drugs.

On the other side of the coin, many of the medications used to treat seizure disorders can trigger depression.  Dilantin, Phenobarbatol, Celonton, Keppra and Tegretol are among those AEDs which are notorious for this side effect.

All very confusing…

“Unfortunately, the media has disseminated this FDA alert in an alarmist manner that may cause unnecessary concern among patients and families. Great caution must be used in the interpretation of an FDA Alert suggesting an increased risk of suicidal ideation and behavior associated with the use of anti-epileptic drugs.

First, it is well-known that many people with epilepsy also suffer from depression and anxiety. Second, stopping anti-epileptic drugs could result in significant worsening of seizures as well as depression and anxiety symptoms. Finally, worsening of symptoms of depression and anxiety are known to occur with starting certain anti-epileptic drugs but this is often temporary. Therefore, it is already part of good clinical practice to monitor the impact of any anti-epileptic drug with regard to psychiatric side effects.”

Andres M. Kanner, MD — Professor of Clinical Neurology, Director of the International Comprehensive Epilepsy Center, Miller School of Medicine, University of Miami, Florida

There you have it in a nutshell — from an internationally recognized authority in psychiatric issues in epilepsy and clinical neurophysiology.

References:

https://www.epilepsy.com/learn/early-death-and-sudep/suicide-risk

https://www.jefferson.edu/about/news-and-events/2021/8/suicide-risk-warning-on-anti-seizure-medications-lacks-evidence.html

http://www.webmd.com/epilepsy/news/20080131/suicide-risk-from-11-epilepsy-drugs?src=RSS_PUBLIC

https://www.tandfonline.com/doi/full/10.1080/14737175.2022.2064744

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108698/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132858/

https://www.who.int/whr/2001/media_centre/press_release/en/

https://www.medpagetoday.com/resource-centers/focus-on-epilepsy/ask-expert-andres-m-kanner-md-psychiatric-comorbidities-patients-epilepsy/1047

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