FDA Wants Black Box Warnings On Epilepsy Meds
8 CommentsBy Ed Silverman // July 7th, 2008 // 3:32 pm
The agency, of course, signaled as much last month when Rusty Katz, the director the FDA’s neuropharmacological drug division, publicly acknowledged the agency has been working on getting suicide warnings in the labeling for 11 meds. Here’s the back story.
Earlier today, though, the FDA made the proposal official in briefing documents posted on the agency website in advance of an advisory committee meeting being held this Thursday to discuss the issue. Here are the documents.
A recent FDA analysis of nearly 200 studies found patients on epilepsy meds were more likely to have suicidal thoughts and behaviors than those on placebo - on average, 0.43 percent compared with 0.22 percent. The agency, however, noted the effect was rare and remain uncertain about the cause. “There seems to be no compelling reason to ignore what appears to be a very clear empirical finding of increase in suicidality, despite no obvious explanation,” Katz writes in the briefing documents.
Lisa Van S
Gee Rusty, It only took you 3 years,… must be so proud of yourself. Ready to accept responsibility for the children who died?,… Probably not, not your style,.. right?
Just A Thought
*rolls eyes*
I started to explain why this study is BS. It was a tedious novella.
Lisa Van S
Just a Thought,
Care to elaborate?
LH
When reading this article, a red flag immediately went up when I saw 0.44% versus 0.22%? That’s pretty low rate. And you don’t think the use of drugs in the psychiatric populations might have skewed things? I couldn’t help but take a look at one of the supporting documents (the FDA’s presentation of the results). I read the 6-page intro, and all I can say is “Blah, blah blah.” The writer gives tenous reasons for even conducting the study in the first place, and weak support for accepting the conclusions.
What it says to me is “We’re under a lot of fire for protecting the safety of the consumer, and if it means we have to invent a reason to slap a black box warning on drugs for an entire therapeutic area (remember, they don’t all have the same mechanism of action), then we will.”
Would love to hear Just A Thought’s specific comments on the BS-ness of the study, since I gave it just a cursory glance.
Justice in MI
I’m finding myself more and more agreeing with those (with whom I don’t always agree) who suggest that the black box may be reaching inflationary proportions.
Of course, the reason it covers whole classes - beyond what is and isn’t known - is that it _may_ make an economic difference if, say, Vioxx had it and Celebrex didn’t (to go back to ancient history).
But given how little attention either docs or pts pay to the warnings in any case, I do wonder whether the saturation point will make it even less likely that these warnings won’t be interpreted as FDA CYA operations rather than genuine warnings, particularly as preemption approaches.
Just A Thought
I’ll try to explain this as briefly as possible. I’ve actually tried twice and it’s neither short nor simple. Keep in mind that my argument only involves the part of the study that deals with epileptics.
I have read “the documents” three times now trying to figure out what I may have missed (if you know please explain it to me). They don’t explain how this study was conducted very well.
What I do know is how epilepsy medications are used in epileptics. The big words in effectiveness are titration and consistency. It takes time, weeks and sometimes months, to find the correct dosage (or even the correct drug) for an individual to achieve a blood serum level that controls seizures without toxicity. Some drugs have to be introduced into the system slowly to avoid other problems. Seizures are terrifying, but don’t play down toxicity, it is poisoning, and someone that is toxic is SICK. Everyone processes these medications differently. Titration is often a nightmare of bouncing back and forth between toxicity and poor seizure control.
There is no placing a person with epilepsy on a placebo. To do so would throw off these precise blood serum levels which were worked out during titration.
This is where I make the mistake of going long explaining the rebound effect of stopping medication (as being given a placebo would do) and possibly placing the consumer into status epilepticus (continuous state of seizure) which can cause brain damage or death. Then I want to get into the other possible things like Simple Partial seizures (for instance), which are localized in one area of the brain and do not cause a loss of consciousness, and which so many people have if they miss one dose or two or three. Simple Partial seizures are basically a possible precursor to a Grand Mal seizure, if this smaller seizure goes beyond it’s localized area of the brain it will cause a larger part of the brain to seize.
If you are stripped of your meds and mess up your titrated blood serum level, for a study, it takes time to get back to your therapeutic range and you are not doing well for that time.
Incidentally, I’d almost bet money that polling a group of healthy teenagers would show more instances of suicidal thoughts.
This is why I found Pharmalot. Pfizer changed Dilantin and threw a percentage of their consumers into the dangerous position of either no control or toxicity. They did it quietly. And while doctors wrote our prescriptions to allow for no substitutions, we were given a substitution because Pfizer kept the same name for their new formula. They are not interchangeable for everyone and it was a horrible and dangerous thing to do. We were given no warning. Just, ‘here’s a new pill’. You can’t just NOT take it because the consequences of not taking it subjects you to the dangers that I very briefly described above.
There were several people who seized or became toxic after years and decades of good control on the old Dilantin Kapseals, formerly produced by Parke-Davis.
Ed was kind enough to write an article about the situation. No one else would after I contacted a countless number of people. I think there was (maybe still is) much confusion about branded drugs vs. generic drugs, but Pfizer added the twist of changing their branded drug to have generic qualities but kept the brand name.
http://www.pharmalot.com/2008/05/a-new-version-of-dilantin-is-giving-pfizer-fits/
All of a sudden we had to find other drugs to titrate onto. My neuro tried me on Lamictal. I had an allergic reaction (weeee, I got to start over). Some of us are still trying to find something that works. Some have successfully titrated onto other drugs.
I was very well controlled for 13 years on Dilantin before Pfizer changed it. I have not been completely well since.
How can a placebo test on epileptics not be BS?
If I have misunderstood this study then I apologize for calling it BS, except that
“The agency, however, noted the effect was rare and remain uncertain about the cause”
Maybe if the FDA would stop approving changes in our medications so that we could be confident to conduct our lives as usual we could see a brighter future? Now TWO drugs used to treat epilepsy have been changed.
If you think my posts here are self serving then you are misreading me. Maintenance drugs should not be changed for anyone. Just that in the case of epilepsy and because of the nature of the condition and our medications, it is particularly dangerous.
LH
Just a Thought, thank you for your comments. Much appreciated. The report does say that data was contributed from 14 epilepsy trials, but some (or nearly all) of them may have had low-dose controls. Placebo-controlled monotherapy epilepsy trials are being conducted less and less these days for precisely the reasons you describe, particularly as there are more medications on the market.
It turns out that the majority of trials were for psychiatric or “other” indications (fatigue, fibromyalgia, etc). But I have to think that neurologic diseases are going to confound the suicide rate somehow, and that you can’t blame it all on the medication. Particularly when the rationale for even accepting the study is so tenuous in the first place (as was very nicely laid out for the author).
I am (very) new to Pharmalot and so I read the Dilantin article for the first time last night. I found it and the comment series very interesting. I, personally, had a very unpleasant experience with Dilantin (2005) that included a severe overdose (required hospitalization) that resulted from a mild change in medication. As you wrote, “titration is a nightmare.” It didn’t take me much longer to say, “Screw it, I’d rather have a seizure.” Fortunately, brain surgery cleared up my need for Dilantin. Lesser of the evils, IMO (and I’m totally NOT kidding, it was so horrible on Dilantin that I would have brain surgery again to avoid it).
Glad Dilantin was good for you, as I know it can be one of the most effective epilepsy medications. I really hope you work out your medication situation. I’ve been/am on several AEDs for various reasons and they can be tough! Most of the side effects have dissipated over time, but every now and then one returns, just for the heck of it, I think. Good luck, and thanks for sharing.
Just A Thought
Nice to meet you LH and welcome to your newest addiction (Pharmalot).
I have contemplated brain surgery- at the utter terror of my family and friends. If the largest percentage of brain surgery patients were able to eliminate AEDs altogether, I’d be in. So many go through it and need dosing anyway. I always appreciate hearing of successes.
Not sure the possibility has been eliminated that people being treated with these drugs for other maladies are not being placed in danger of rebound seizures even if they do not have epilepsy, simply for stopping their medication. It’s worrysome. It is also a bit of a trap if that possibility exists.
Curious if studies have been conducted in this area or if we just have to wait it out and see. I’m not real trusting of studies anymore anyway, but does anyone know?