How does aeds get accepted

[notime]

Hey,

I was looking at how anti-epileptic drugs work in the brain, but I found many people saying they didn't know how it worked. They say they assume that it calms over excitable neurons in the brain but they are not really sure... How do drugs, without an understanding of how it works in the brain get figured out to control seizues? I mean, if they don't know how it works, how does the FDA come up with ways to approve it and so forth?

Sorry, I am just curious, even my neurologist couldn't completely say how it controlled seizures. But, if they don't know, how does the fda accept it, if they don't know what the risks are or what it does in the long term?

 

[Bernard]

The scientists at big pharma labs have some idea of what each drug is doing in the brain. When they identify a drug that has the potential of stopping seizures, they get some clinical trials to establish empirical evidence.

What you need to understand though is that "epilepsy" encompasses a wide range of seizure conditions - conditions that don't all share the same pathology. There can be many different (physical, chemical, biological) causes for seizures to develop.

A drug designed to block/stabilize a particular ion channel, for example, isn't going to stop or affect seizure activity that manifests from a different cause.

Most clinical trials even try to narrow down the type of seizure that the drug is treating - like limiting participants to those with complex partial seizures (not tonic clonics or myoclonics, etc.). Even so, no drug, no matter how effective, works for everyone in the target group.

 

[masterjen]

Hi, Bernard
I have often wondered what notime asked as well. Can you elaborate on your comment that epilepsy can have physical, chemical, or biological causes. What might be included in each category? I was "excited" to read this phrase, as it might finally give me some understanding of what type of epilepsy I have.

 

[sassi]

I would chance to say that the meaning behind that would be physical (i.e., accidents, getting kicked in the head, hit in the head, etc), chemical (i.e., drugs in your history. My first grand mal seizure when I was was cross-buzzing with mj and alcohol), and biological (i.e., being born with them, for lack of a better phrase. Inherited or otherwise passed through your genes).

I could be totally off base with that but I think that's what was meant by that. I believe that most scientists end up having some sort of knowledge of what the drug does over time. Granted, it's different for everyone due to their inherent chemical make-up but it's an over-generalization. That's why neurologists' sometimes have to play with medications in order to get it to work right with your biology and how your body processes things. It's like any other medication, except working with your brain.

There are extensive tests done (some drugs I wonder why they're still putting out in the general public given some of the side effects, to be honest) before they put a drug out there. Personally I still feel like I should still research the drug anyhow until I know so much about the side effects it's just as scary as being off the drug.

masterjen, I don't know if there's any way to really understand what kind of epilepsy anyone has other than an educated guess, really. It's an inexact science, from what I've read here, because there are so many different types of seizures and different circumstances around them. Maybe your neurologist has an idea? I asked my doctors and they said that sometimes there just aren't any answers. It frustrates me to no end, not having answers, but sometimes that's the reality of the situation.

 

[Cint]

I would chance to say that the meaning behind that would be physical (i.e., accidents, getting kicked in the head, hit in the head, etc), chemical (i.e., drugs in your history. My first grand mal seizure when I was was cross-buzzing with mj and alcohol), and biological (i.e., being born with them, for lack of a better phrase. Inherited or otherwise passed through your genes).

I could be totally off base with that but I think that's what was meant by that.

I would say that you are totally off base with that analogy.

I started having seizures "out of the blue" when I was 22 years old. I never had a head injury, never had meningitis, encephalitis or any of those type of illnesses when my seizures started. I didn't do hard drugs in college or any other time in my life nor was I born with E. I'm the only one in the family, other than a cousin, who has E. I've been thru numerous AEDs, had brain surgery, and three VNS surgeries. I was once on a trial drug study, to no avail. One dr. even asked if there was child abuse in my upbringing, because of the stress that goes along with abuse can/does effect/damage the brain. And then I was told that I had catamenial E, caused by hormonal changes that women go thru. That was true until after I had brain surgery, then my hormones really went haywire and so did my seizures! And now that I've been thru menopause, the seizures have eased, but they haven't completely stopped. Some of us have refractory E, meaning it will forever be with us, unfortunately. And with several different types of seizures to deal with it, it is extremely difficult to control.

Here is more info on clinical trials:
http://www.centerwatch.com/clinical-trials/overview.aspx?mp=epilepsy

 

[sassi]

I would say that you are totally off base with that analogy.

I started having seizures "out of the blue" when I was 22 years old. I never had a head injury, never had meningitis, encephalitis or any of those type of illnesses when my seizures started. I didn't do hard drugs in college or any other time in my life nor was I born with E. I'm the only one in the family, other than a cousin, who has E. I've been thru numerous AEDs, had brain surgery, and three VNS surgeries. I was once on a trial drug study, to no avail. One dr. even asked if there was child abuse in my upbringing, because of the stress that goes along with abuse can/does effect/damage the brain. And then I was told that I had catamenial E, caused by hormonal changes that women go thru. That was true until after I had brain surgery, then my hormones really went haywire and so did my seizures! And now that I've been thru menopause, the seizures have eased, but they haven't completely stopped. Some of us have refractory E, meaning it will forever be with us, unfortunately. And with several different types of seizures to deal with it, it is extremely difficult to control.

Here is more info on clinical trials:
http://www.centerwatch.com/clinical-trials/overview.aspx?mp=epilepsy

Ah okay, yeah. I wasn't meaning that everyone is under that umbrella. Some people there is no definite point where they start. I was 6 months out from that time before I had more of them and they weren't the same type I had back in July of last year. Some people will always have them, that I've been learning looking through here -- and it's like a guessing game it seems, to figure out what is causing them. Seizures are so unpredictable.

I was never told what exactly caused mine, nor do the doctors have any idea. Even when I asked point blank whether or not the incident in July caused them. Too inexact a science, really. Being completely honest, it's very odd that they just start up out of the blue, you know? You would think there would be a cause they could tell you. Might make you feel a bit better.

notime, have you asked your neurologist about how they're tested and accepted? Not sure if the doctor would have any more knowledge about that than doing your own research.

 

[Cint]

Being completely honest, it's very odd that they just start up out of the blue, you know? You would think there would be a cause they could tell you. Might make you feel a bit better.

Sorry, I didn't word it correctly. What I meant was that my TC seizures didn't start out of the blue. I had been having these "spells" where I would just stare into space and couldn't speak for a minute or two and feel strange. They were going on for several days a week for several months. When I went to the dr., he made the diagnosis of hypoglycemia without any testing. What I really was experiencing was CP seizures. About 5 months later, I had my first TC seizure "out of the blue". I hadn't been tested yet or put on any meds for seizures at the time. While in the hospital, they did test after test and could never tell me why or where the seizures came from. They call it "idiopathic" E.

 

[sassi]

Sorry, I didn't word it correctly. What I meant was that my TC seizures didn't start out of the blue. I had been having these "spells" where I would just stare into space and couldn't speak for a minute or two and feel strange. They were going on for several days a week for several months. When I went to the dr., he made the diagnosis of hypoglycemia without any testing. What I really was experiencing was CP seizures. About 5 months later, I had my first TC seizure "out of the blue". I hadn't been tested yet or put on any meds for seizures at the time. While in the hospital, they did test after test and could never tell me why or where the seizures came from. They call it "idiopathic" E.

Oh! Okay. I've had "spells" where I can't speak for a bit but I can hear what's going on or I'm talking then I get "cut off" and can't talk for a little bit than I can talk again. It's like I'm trapped inside my own mind but my brain doesn't really work right, I'm just sitting there and I can hear everything and see everything but I don't respond.

Tonight was particularly not fun when I woke up to my hands cramping like t-rex fingers and then my window on the far wall was getting bigger and my dog's face got weird and then this dresser on the other wall got bigger too. My fingers, arms, hands, and legs have been twitching on and off since I got off work today. I'm almost afraid to go back to sleep because i don't want to wake up to my walls doing that again or my dog's face, scared me so bad. Plus this stupid headache.

My hands still aren't really relaxed. Ugh. I hate that looking at seizures and for seizures is an inexact science. makes life for those of us with them far more difficult than anyone could ever imagine. What really sucks is when doctors and other medical professionals just make diagnosis' without doing any testing at all or really even looking at everything that's gone on in a patient's history.

 

[Cint]

I mean, if they don't know how it works, how does the FDA come up with ways to approve it and so forth?

Sorry, I am just curious, even my neurologist couldn't completely say how it controlled seizures. But, if they don't know, how does the fda accept it, if they don't know what the risks are or what it does in the long term?

Through clinical trials. The testing begins in labs thru experimentation in animals and human cells. That can go on for years. Once it is approved for human testing, it is done in 4 stages. It has to pass each of these 4 stages before being approved by the FDA.

Phase I: The initial phase of the testing; it assess the safety of the drug and how it is absorbed, metabolized, and excreted. Also side effects as the dosage is increased.

Phase II:Tests the efficacy of the drug. It can last up to two years and involves several hundred patients. One group receives the the experimental drug and one group receives a placebo. These are "blinded" studies. Neither the patient nor the researcher knows who has received the placebo and who has received the clinical drug.

Phase III: This is a large scale testing, involving several 1000 patients. It lasts several years, providing the pharmaceutical and the FDA a more thorough understanding of the drug. The pharmaceutical can request approval from the FDA at this point for marketing of their drug.

Phase IV: Post Marketing Surveillance Trials are conducted after the drug has been approved. Phase IV studies can also result in the meds being taken off the market or for restrictions of use could be placed on the drug, depending on further findings.

( I had this happen to me from a drug that was on the market for depression in the Japan for several years, but they took it off the market because people died from it and others ended up with Type 1 Diabetes. In the U.S, it is still on the market but with a black box warning- it can cause diabetes. I now have Type 1 Diabetes from this stupid drug!!)

 

[Bernard]

I would chance to say that the meaning behind that would be physical (i.e., accidents, getting kicked in the head, hit in the head, etc), chemical (i.e., drugs in your history. My first grand mal seizure when I was was cross-buzzing with mj and alcohol), and biological (i.e., being born with them, for lack of a better phrase. Inherited or otherwise passed through your genes).
...

I would say that you are totally off base ...

Nope, sassi was on base.

For some people, epilepsy is clearly associated with scar tissue in the brain that may or may not be traceable to an accident (head trauma). This would be a physical issue (scar tissue).

For some people, epilepsy (or more properly just seizures) is clearly associated with blood sugar disorders / diabetes, homeostasis, etc. This is what I meant by a biological issue.

For some people, epilepsy/seizures is clearly associated with drugs they are taking (or overdosing on).

That's not to say that everyone with epilepsy will be diagnosed with any of those issues. My point was just that "epilepsy" covers a pretty wide spectrum.

 

[Cint]

That's not to say that everyone with epilepsy will be diagnosed with any of those issues. My point was just that "epilepsy" covers a pretty wide spectrum.

:agree: But not all with Diabetes have diabetic seizures. That's where my first idiot dr. made a mistake years ago and I wasn't even experiencing hypoglycemia or diabetes! And not all people who have seizures have abused drugs, either. That is what I got from Sassi's explanation of "chemical". Plus not all are born having seizures. As said before, for some, there is NO reason.

 

[daviscy60]

:agree: But not all with Diabetes have diabetic seizures. That's where my first idiot dr. made a mistake years ago and I wasn't even experiencing hypoglycemia or diabetes! And not all people who have seizures have abused drugs, either. That is what I got from Sassi's explanation of "chemical". Plus not all are born having seizures. As said before, for some, there is NO reason.

I have to agree with Cint on this one. Started having seizures at age 18 / 19. Home alone would get strange feeling then next picking myself up off the floor. Was not sure what it was. Happened several times then one Sunday started happening while at home with husband. Spent the day watching football and me sleeping most of the day didn't really remember going to bed that night. Had my first grand mal while sleeping. After visit to ER and neuro no one could tell me how or why they started. I had never touched anything stronger than maybe a little alcohol... No drugs at all. Nothing not even alcohol prior to seizures. Around the age of 23 asked a neuro if hormones or BC pills could be the cause and answer was no. This I still disagree with somewhat. Maybe there was a slight defect and maybe the hormones provoked it??? Whatever the case. I'm still on AED's and have always been told they do not know the cause. I also have a really hard time finding out what may trigger them. What seems to trigger it at one time I can do the same and have no problems.

 

[sassi]

No, no, no. That's not what I had been implying at all. I wasn't putting everyone with epilepsy under a blanket in the slightest. The causes are too vast and unknown to understand what actually causes E and what doesn't cause E so I think there was some misunderstanding. I was trying to clarify what Bernard said not put everyone with E under some magical, mystical blanket of diagnosis because if that were the case the doctors would've penciled me off as "you shouldn't have done what you did back in July" and not given me any medications at all, or at least they shouldn't have. Nor should I have had any more seizures. So do I have an answer for my own seizures? No, it's not cut and dried like that and I wasn't implying, nor did I mean to come off implying that. If I did I'm deeply apologetic for doing so because that definitely wasn't my intent.

As far as I know, mine could be a mixture of anything plus what happened last year; who knows? Not me, not my doctors. My blood tests since have come back within the normal ranges and there isn't anything overly strange going on in my life other than seizures.

Again, it was never my intention to say that I was putting everyone under this magical blanket and if I came across like that I apologize from the bottom of my heart as I never meant to. I was just trying to clarify what Bernard was trying to say. ^^ Because I know damn well that E isn't as cut and dried as that.