It led to the report published this month by England’s patient safety commissioner, Dr Henrietta Hughes, which recommended a compensation scheme for families of children harmed by valproate taken in pregnancy.
Valproate is not just for epilepsy; it's also used for bipolar disorder and migraines. For people who only know the brand names of their medications or don't have even a layperson's grasp of the kinds or classes of medications they are or were on (cos a lot of physicians don't explain any of this, or the side effects) they might miss that this could apply to them too.
Seems like most doctors rely on an Epic printout handed to the patient at checkout time, or the fact sheet provided at the pharmacy. How many people read those, let alone understand them?
For valproate, there are multiple forms that result in the same active ingredient. Then there are multiple brand names for each form since it has generics, and brand names are different in each country.
I briefly took Divalproex for migraines which is sodium semivalproate. My doctors called it Depakote since that was most common brand name. Two names was enough trouble finding information. I didn't realize it was valproate until now.
Why? These organisations only purport to be acting for 'the people' whilst actually working for the pharmaceutical organisations. They are there to provide the illusion of safeguards.
Because the other epilepsy drugs carry similar risks. So they leave it as an option since the individual risk profile depends on the effectiveness and efficacy of the other drugs for that specific person. Even the "safe" standard (keppra) has these risks today.
That's just for the effects on child IQ, which apparently came out of a new study around that time.
It says at the bottom that the other fetal risks have been known for a long time.
"Valproate products have long been known to increase the risk of serious birth defects, in particular, neural tube defects such as spina bifida. This risk is already described in detail in the drug labels for valproate products."
>the Committee on Safety of Medicines (CSM), then the main decision-making body on new medicines, which concluded that the risk was low and that patients should not be informed, in order to avoid “fruitless anxiety”
Ah, well, at least no one experienced any fruitless anxiety.
Same thing with basically all meds. Just look at how hormonal birth control is handled - risk of pregnancy is considered to outweigh risks of vascular issues, cancer risks (gliomas), etc and patients usually have no idea about the risks. The doctors have made that risk assessment for them. Even over OTC meds have risks that most patients don't know about, or care about, until it affects them.
Hormonal birth control is extremely common and generally presents minor issues. This is a relatively uncommon anti-seizure drug that has extremely high risks of causing developmental issues in children.
Sure, if you compare anything to hormonal birth control it will be relatively uncommon - they hand that stuff out readily and even consider making it OTC. This antiseizure drug is still commonly prescribed in many countries.
"extremely high risks"
A 700% on a 1.6% base rate, right? How does that compare with cumulative risk increases for cancers or vascular issue with hormonal birthcontrol? For example, they see a 60% increase in cervical cancer risk alone. That's pretty significant too if it's not being disclosed for patients to make an informed decision.
Keep in mind, my argument was never that the risk of hormonal birth control were more than this drug or any other drug. My argument is that patients are still not informed of substantial risks that may not be as readily apparent as the minor issues that are more common.
While I agree that medical communication can and should be better, it’s worth pointing out that hormonal birth control also lowers the risk of endometrial, ovarian, and colorectal cancer by a similar amount according to cancer.gov (see: https://www.cancer.gov/about-cancer/causes-prevention/risk/h...).
That's true, and to some extent useful, as people are generally pretty bad at risk evaluation.
At the same time, drugs with teratogenic effects "feel" like a special case. The risk isn't just to the patient, but to their unborn child. And pregnancy can be successfully avoided.
I don't know where to draw the line, but at least based on a quick read of the linked article and a few related pieces, it feels like NHS and other government bodies (both UK and elsewhere) dropped the ball with this drug.
"The risk isn't just to the patient, but to their unborn child."
Any reasonably adept provider should be considering the care for the fetus (assuming it isn't being terminated). The main problem in this case was the lack of disclosure. And those disclosure problems are widespread.
Anti seizure meds specifically are tricky. If you are on these meds and plan to become pregnant, they all increase defect risks. While some have lower risks, the effectiveness of the drugs can be highly specific to the individual. Some individuals may be required to take the higher risk drugs is the current low risk standard doesn't effectively control thier issue.
Absolutely. If seems like this drug should have been placed on the "high risk - don't take while trying to conceive" lists from the outset. And from what I can tell, it's only on that list in the US when being prescribed for migraine control (but not seizure control).
This will sound callous, but sometime a person has to pick between managing their personal health and having a child. I have a friend who's on some nasty drugs and when faced with the choice between "go off drugs, relapse", "stay on drug, risk birth defects", and "stay on drug, don't have a kid" she chose the last option (correctly IMO, but it's definitely not my place to interject).
"If seems like this drug should have been placed on the "high risk - don't take while trying to conceive" lists from the outset. And from what I can tell, it's only on that list in the US when being prescribed for migraine control (but not seizure control)."
That's because they're doing the risk profile. Seizures pose a risk to the fetus too while migrains do not. So they aren't doing it based solely on risk, but on the overall risk profile including "rewards" or reduction in other risks.
Sorry, I wasn't clear - it sounds like they may have botched the risk profile - the article paints a picture where the real-world incidence/severity of defects is "high".
But, they're selling clicks, and the patients are looking for money/support, so it's hard to know for sure. It certainly seems like there should have been a discussion between MD and patient here (similar to what my friend had with her MDs, albeit different drugs/condition).
In the United States this medication has a black box warning about fetal damage.
For those who are elsewhere, a "black box warning" is the most serious warning the United States Food and Drug Administration can require -- it's called that because they mandate that the manufacturer print the warning at the top of the package insert, surrounded by a black box to draw attention.
I agree, and the risks go beyond personal health. It doesn't help that it's politicized and used as a tool to win votes (on either side) as a right that establishes your freedom/strength as a woman.
I couldn't even have a conversation with most women about any of the negative effects.
The effects of hormonal birth control had have trickled and Id argue they influence and effect every part of our society greatly.
Her children's development has been greatly altered and will completely change the course of their lives and the lives around them. I can only imagine, but I feel a sense of helplessness for her.
The risks of hormonal birth control are widely known. They are clearly stated in the package insert, and a lot of doctors will discuss them with you and offer alternatives if you're worried about it.
But indeed, for a lot of women a pregnancy would be far riskier than the side effects of birth control.
I guarantee they are not all on there. For example, risks of glioma related to progestin, or cervical cancer risks. This type of scenario is the entire basis of the article.
Most patients (and many doctors) make the choice without reading the insert anyways. The insert is generally not provided to the patient prior to purchase and most don't care read it anyways due to other concerns.
"But indeed, for a lot of women a pregnancy would be far riskier than the side effects of birth control."
For a subset, sure. But for the majority of women prescribed (young and generally healthy), that statement may not be true. The majority of contraceptive use is primarily of social desire. Medical necessity is a secondary concern. We can easily see this in the fact that most women are never consulted about the medical risks of either scenario when requesting birthcontrol and an overall consultation on possible options is usually limited and in some cases absent (although it has been improving as more options become more mainstream).
who deems them experts? what does it take to be an expert? are experts ever wrong? History is filled with experts who were wrong. History is also filled with experts who can't even admit they were wrong. Why should I put blanket trust in someone just because someone else calls them an expert?
To be clear, I'm not arguing the validity of the position of "trust experts", I' arguing the inanity of encouraging people to trust experts who have taken the position of lying, out of their professional expertise.
“The NHS was saying they didn’t have that information and there was insufficient research,”
They (and other government bodies) say this about all sorts of medications that have limited support for any harm. If generally safe is the default, proof of harm has a higher bar to dethrone the existing raring.
One thing I didn't see in the article was what the alternative meds were and their safety profiles.
Guess what? Keppra is now the standard and touted as the safest during pregnancy and that breasrfeeding while on it is still recommended. It's also listed as having potential tetrogenic issues. So this type of issue is still strong today.
This is devastating and I don't want to take away from it but this sort of thing is even worse than just the families affected by it.
Many people distrust authority for reasons like this. These same people will turn around and get frustrated that so many didn't trust them about the safety of covid vaccines (and other types of vaccines).
They do themselves no great service by not being more honest and forthright in the first place.
Wrote Hacking Healthcare, former hospital system administrator, blah, blah...
I think the comparison to thalidomide is click bait. Thalidomide was such a problem because it was used to treat symptoms of pregnancy, not some other unrelated condition. In this situation all(?) of the first line pharmaceutical treatments for managing epileptic seizures pose at least some developmental risk to unborn children. On the other hand unmanaged epileptic seizures also pose a risk to the parent and child.
This was a situation of gross negligence on the part of the institutions involved in regulation AND the direct providers offering care. A classic "somebody else's problem" field. Institutions failed to identify the actual scale of the risks involved in a way that properly educated providers and providers chose an inappropriate framework with which to manage and communicate the risks to patients who could or did become pregnant.
The drug involved here is not really the problem, it is an effective drug at managing epileptic seizures. A reasonable approach that was not employed would be to properly identify the drugs serious dangers to developing children in those who may become pregnant to providers. As a regulator you need to hit them over the head with it. From a course of treatment standpoint selection of alternative drugs for patients who would like to become pregnant that have slightly less risk to undeveloped children need to be prioritized. Providers need to make sure that proper supplementation happens (folic acid, etc). The risk is meaningfully reduced and the patient would better understand what can happen. This type of comprehensive and nuanced course of treatment is something that is just very very difficult for healthcare, in the US anyway, to achieve.
> They also found the response from the Committee on Safety of Medicines (CSM), then the main decision-making body on new medicines, which concluded that the risk was low and that patients should not be informed, in order to avoid “fruitless anxiety”.
That's interesting, because in the United States this stuff has a "black box warning" that warns in no uncertain terms about fetal risk.
39 comments
[ 4.5 ms ] story [ 95.9 ms ] threadI briefly took Divalproex for migraines which is sodium semivalproate. My doctors called it Depakote since that was most common brand name. Two names was enough trouble finding information. I didn't realize it was valproate until now.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...
It says at the bottom that the other fetal risks have been known for a long time.
"Valproate products have long been known to increase the risk of serious birth defects, in particular, neural tube defects such as spina bifida. This risk is already described in detail in the drug labels for valproate products."
Ah, well, at least no one experienced any fruitless anxiety.
Sure, if you compare anything to hormonal birth control it will be relatively uncommon - they hand that stuff out readily and even consider making it OTC. This antiseizure drug is still commonly prescribed in many countries.
"extremely high risks"
A 700% on a 1.6% base rate, right? How does that compare with cumulative risk increases for cancers or vascular issue with hormonal birthcontrol? For example, they see a 60% increase in cervical cancer risk alone. That's pretty significant too if it's not being disclosed for patients to make an informed decision.
Keep in mind, my argument was never that the risk of hormonal birth control were more than this drug or any other drug. My argument is that patients are still not informed of substantial risks that may not be as readily apparent as the minor issues that are more common.
At the same time, drugs with teratogenic effects "feel" like a special case. The risk isn't just to the patient, but to their unborn child. And pregnancy can be successfully avoided.
I don't know where to draw the line, but at least based on a quick read of the linked article and a few related pieces, it feels like NHS and other government bodies (both UK and elsewhere) dropped the ball with this drug.
Any reasonably adept provider should be considering the care for the fetus (assuming it isn't being terminated). The main problem in this case was the lack of disclosure. And those disclosure problems are widespread.
Anti seizure meds specifically are tricky. If you are on these meds and plan to become pregnant, they all increase defect risks. While some have lower risks, the effectiveness of the drugs can be highly specific to the individual. Some individuals may be required to take the higher risk drugs is the current low risk standard doesn't effectively control thier issue.
This will sound callous, but sometime a person has to pick between managing their personal health and having a child. I have a friend who's on some nasty drugs and when faced with the choice between "go off drugs, relapse", "stay on drug, risk birth defects", and "stay on drug, don't have a kid" she chose the last option (correctly IMO, but it's definitely not my place to interject).
That's because they're doing the risk profile. Seizures pose a risk to the fetus too while migrains do not. So they aren't doing it based solely on risk, but on the overall risk profile including "rewards" or reduction in other risks.
But, they're selling clicks, and the patients are looking for money/support, so it's hard to know for sure. It certainly seems like there should have been a discussion between MD and patient here (similar to what my friend had with her MDs, albeit different drugs/condition).
For those who are elsewhere, a "black box warning" is the most serious warning the United States Food and Drug Administration can require -- it's called that because they mandate that the manufacturer print the warning at the top of the package insert, surrounded by a black box to draw attention.
I couldn't even have a conversation with most women about any of the negative effects.
The effects of hormonal birth control had have trickled and Id argue they influence and effect every part of our society greatly.
Her children's development has been greatly altered and will completely change the course of their lives and the lives around them. I can only imagine, but I feel a sense of helplessness for her.
Just don't do drugs is all i feel to say.
But indeed, for a lot of women a pregnancy would be far riskier than the side effects of birth control.
I guarantee they are not all on there. For example, risks of glioma related to progestin, or cervical cancer risks. This type of scenario is the entire basis of the article.
Most patients (and many doctors) make the choice without reading the insert anyways. The insert is generally not provided to the patient prior to purchase and most don't care read it anyways due to other concerns.
"But indeed, for a lot of women a pregnancy would be far riskier than the side effects of birth control."
For a subset, sure. But for the majority of women prescribed (young and generally healthy), that statement may not be true. The majority of contraceptive use is primarily of social desire. Medical necessity is a secondary concern. We can easily see this in the fact that most women are never consulted about the medical risks of either scenario when requesting birthcontrol and an overall consultation on possible options is usually limited and in some cases absent (although it has been improving as more options become more mainstream).
They (and other government bodies) say this about all sorts of medications that have limited support for any harm. If generally safe is the default, proof of harm has a higher bar to dethrone the existing raring.
One thing I didn't see in the article was what the alternative meds were and their safety profiles.
Guess what? Keppra is now the standard and touted as the safest during pregnancy and that breasrfeeding while on it is still recommended. It's also listed as having potential tetrogenic issues. So this type of issue is still strong today.
This has a lot more concrete info if you are looking for it from the story.
Many people distrust authority for reasons like this. These same people will turn around and get frustrated that so many didn't trust them about the safety of covid vaccines (and other types of vaccines).
They do themselves no great service by not being more honest and forthright in the first place.
I think the comparison to thalidomide is click bait. Thalidomide was such a problem because it was used to treat symptoms of pregnancy, not some other unrelated condition. In this situation all(?) of the first line pharmaceutical treatments for managing epileptic seizures pose at least some developmental risk to unborn children. On the other hand unmanaged epileptic seizures also pose a risk to the parent and child.
This was a situation of gross negligence on the part of the institutions involved in regulation AND the direct providers offering care. A classic "somebody else's problem" field. Institutions failed to identify the actual scale of the risks involved in a way that properly educated providers and providers chose an inappropriate framework with which to manage and communicate the risks to patients who could or did become pregnant.
The drug involved here is not really the problem, it is an effective drug at managing epileptic seizures. A reasonable approach that was not employed would be to properly identify the drugs serious dangers to developing children in those who may become pregnant to providers. As a regulator you need to hit them over the head with it. From a course of treatment standpoint selection of alternative drugs for patients who would like to become pregnant that have slightly less risk to undeveloped children need to be prioritized. Providers need to make sure that proper supplementation happens (folic acid, etc). The risk is meaningfully reduced and the patient would better understand what can happen. This type of comprehensive and nuanced course of treatment is something that is just very very difficult for healthcare, in the US anyway, to achieve.
That's interesting, because in the United States this stuff has a "black box warning" that warns in no uncertain terms about fetal risk.
http://editor.fresenius-kabi.us/PIs/US-PH-Valproate-Sodium-I...