What The FDA Says About Epilepsy Meds & Suicide
7 CommentsBy Ed Silverman // June 11th, 2008 // 6:59 pm
For the past two weeks, reports surfaced that drugmakers are trying to come to grips with FDA plans to increase warnings on 11 epilepsy meds about suicidal thoughts and behavior. One agency official cited a combined analysis of 199 clinical trials that included 43,892 patients showing an “across the board” trend in differences in behavior between patients on placebo and those on the meds.
Now, though, a May 23 FDA report, which will be discussed at a July 10 advisory committee, was posted on the agency web site today. The conclusion, of course, has been well telegraphed: “antiepileptic drugs are associated with increased risk of suicidality relative to placebo in randomized placebo-controlled trials. The effect appears consistent among the group of 11 drugs.”
For those who want to delve into the details, you can look right here. Meanwhile, these are some other observations: “The higher risk of events for the drug-treated patients was observed as early as one week from initiating treatment until at least 24 weeks. After 24 weeks, it was not possible to draw conclusions due to the scarcity of data beyond 24 weeks.”
“The epilepsy indication subgroup had the largest estimated odds ratio compared to the psychiatric indication subgroup and the other indication subgroup. However, the psychiatric indication subgroup had the largest placebo risk of events.”
“There were four completed suicides among drug patients and none among placebo patients. The majority of suicidality events for both drug and placebo patients were suicidal ideation. The second most frequent type of event was suicide attempt. Without adjusting for differences among trials, 0.37 percent of the drug patients had a suicidal behavior or ideation event versus 0.24 percent of the placebo patients.”
Doug Bremner
I’m glad to see that people are starting to understand that medications with effects on the brain can have depression and suicidality as a side effect. Maybe now we won’t have to listen as much to the comment ‘it’s an epilepsy drug, how can it cause depression?’ or ‘it’s an asthma drug (Singulair) how can it cause depression/suicidality?’ The neglect of psychiatric side effects of prescription medications used to treat physical disorders is just another example of stigma related to mental disorders. Too bad for the families that got burned.
Perks
Well said DougB. Though asthma drugs, steroids, painkillers, antihistamines and the rest are not at times seen as having an effect on the brain, but trusted as simple medication for a precise purpose.
M Helm, MD
Thank you Ed for this report and the helpful link.
Table 16 in the report is quite interesting. It provides a more clear picture of what is described in paragraph five above.
Basically, if you were in a psychiatric trial and you received the study med, the rate of a “suicidality event” was 8.5 per 1000 patients. If you received placebo in that trial the rate was 5.7 per 1000. In other words, The active medication is associated with observing a higher rate of “suicidality” events.
If on the other hand you were in a trial treating seizures, and received the study med, the rate of events was 3.4 per 1000 patients. If you had the placebo, the rate of suicidality events was only 1.0 per 1000.
There is a greater odds ratio comparing placebo to drug in the epilepsy trials. However, the greatest actual risks are in patients treated for psychiatric conditions, and receiving the drug is associated with an already elevated risk.
The analysis also shows, in another table, that young patients may have had a higher odds ratio for events on treatment compared to placebo than older patients up to age 65. There is a wide confidence interval on most of the age groups consequent smaller numbers of patients in trials. All but adults aged 31 to 64 overlapped the equal odds point of 1 so while we can’t truly know if the estimate actually shows a difference or not, it does not trend the “good” way.
Other charts show the odds ratios for the individual compounds. Topirimate seems to have the highest odds ratio, and the confidence interval makes this appear to be a real difference. Lamotrigine in next worst in the original analysis, though slightly redeemed by supplemental data provided by the company.
I know there is wide popularity of using seizure medications (particularly topiramate, lamotrigine, and to a seemingly lesser extent divalproex)for behavioral disturbances/”bipolar” disorder in children. The disturbing conclusion I’m taking away is that it looks like kids are once again at significant increased risk from a (purportedly helpful) intervention for a “condition” which the preceding generations did not recognize.
Thanks Dr. Bierderman (and Co)! (I know - sarcasm does not scan in text.)
Laurie
“The neglect of psychiatric side effects of prescription medications used to treat physical disorders is just another example of stigma related to mental disorders.”
You are SO right on with this statement! The majority of patients who report a psychiatric side effect are written off as “crazy, bipolar, anxious, depressed” even when the original reason for the drug had NOTHING to do with any of those symptoms.
This not only does a diservice to those who have this reaction, but an even worse diservice to those with a true mental illness diagnosis. I hear about this time and time again….the report of suicidal thoughts are dismissed as “you need more of the drug”, when suicidality was never an issue prior to the drug. Those with a documented mental illness have side effects just like everyone else in the general public, but sadly, once diagnosed they become a non entity with their symptoms dismissed as “part of the the illness”. So while the advocates claim to be trying to destigmatize mental illness, this situation increase that stigma.
Chantix is the classic example of denial of emerging side effects. Those who report these new onset symptoms are dismissed as “hidden” psych patients.
The attitude is dangerous.
Doug Bremner MD
I think it is malpractise and totally irresponsible for the makers of Chantix to say that it is OK for people with a history of depression or other mental disorders to take their drug when their clinical trials excluded people with mental disorders and when their drug affects the frontal lobe and obviously influences behavior.
Their drug works because it affects the brain area involved in emotion/addiction (frontal lobe), also depression/suicide (duh!).
I mean the chance of dying from suicide might be less than cancer for Chantix users, but at least they should know what they are getting into.
Door prize for drugs that might drive you crazy is Larium (malaria prophylaxis) with psychiatric side effects in over half of people who take it.
Just A Thought
If you think this is helpful, think again.
It is interesting that the FDA can compile those numbers but they cannot gather and act on the multiple bad reactions reported to MedWatch concerning these drugs. Or is this their idea of a proper reaction?
It is also interesting that their study was not just the MUCH lessor study the FDA requires to approve an ANDA or sANDA before a manufacturer quietly releases an altered med to the public.
To fully understand what a big deal that is, you must read this…
http://www.fda.gov/OHRMS/DOCKETS/AC/99/slides/3547s1i.pdf
This action is self serving on the FDAs part, in my opinion. When people question the FDA approvals of medications (or changes in those meds), their course is to plop a blanket warning on the condition (not just on the drugs). It protects them by allowing them and the pharmaceutical companies to dismiss the patient as possibly unstable when they have dangerous reactions.
Read between the lines.
You are given a drug that makes you horribly ill, you report it, you find others who are reporting the problems too. You get a form letter that says that the FDA MAY investigate the problem if they get 1 or 2 well documented reports. Months later nothing is done but to say… Epileptics are a depressed group by nature.
The legal argument?… Depression can manifest itself in physical ways. The victim is hobbled legally.
The industry can feed us anything they want and there is no recourse because, hey, there’s a warning on the label?
This action is a cop out. There are a few million people with epilepsy in this country (and I’m not even touching the migraine or bipolar folks being treated with these meds). If people are left without help from those they trust to protect them, maybe they can muscle through seizures, toxicity, brain damage, nerve damage, job losses, the inability to care for their families… for a little while. Maybe the lack of support is more the problem than the illness itself. Is it really the illness that is causing hopelessness?
I am obviously beating a dead horse.
Just A Thought
I must add that the link I provided above mentions the differences in branded and generic drugs. Dr. Schachter’s comments were made before Dilantin was altered to have genric qualities. I cannot imagine that he could support the changes in Dilantin, as to be switched at all, goes against his worthy argument.