6 ms·

Sorry for the potentially insensitive question, but I really am wondering about this: >One side effect I should mention: many report extreme anxiety. However,

Sorry for the potentially insensitive question, but I really am wondering about this: >One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me. I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?

therein 3y ago
Just an anecdotal experience so doesn't necessarily mean anything but the only person I knew that had CF had absolutely no anxiety from his condition. If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.
mason55 3y ago
> I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety? There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal. So it seems to be a bit of an open question and I'm sure an emotional one on both sides.
- ipaddr 3y ago
  Clinicians are always a day late and a dollar short. The evidence comes from these people reporting. These clinicians need a 50 million dollar grant to get that proof.
  - TechnicalVault 3y ago
    If you've ever had to organise a scientific study you'll understand why. Privacy and ethics are important but they make recruitment of a large and representative sample for any medical study a nightmare. First you'll need to run your protocol past an ethics board and do back and forth until it's agreed. Once you have that done you'll send out an invite (often blind) in hopes of getting people who fit your study aims and you will get who you get. There are often costs associated with this. So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses. Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion. tldr; medical and scientific studies are hard if you want them to actually have any validity.
    - pas 3y ago
      wouldn't this side-effect become visible in Phase4 data? (and there should be at least some hints of this in the previous ones) so, what I'm trying to say is that for this particular drug we "just need to wait", no?
    - AdamN 3y ago
      It seems like we really need to move forward to 'indefinite/active studies'. I believe some researchers are trying to get onto this pattern but of course there are major privacy/quality of care concerns. By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).
      - 3y ago
vkou 3y ago
People generally get acclimated to the situation they are in. If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.
- pfannkuchen 3y ago
  You might even have more with 15M! It’s much harder to replace if you lose it.
- fnordpiglet 3y ago
  I grew up with a lot of money insecurity, was homeless for a while and started my career with nothing - one change of clothes and a floor to sleep on. I’ve since done very well for myself and have a considerable amount of net worth at this point and a lucrative forward for as long as I want to keep working at it. I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had. That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.
  - TotalCrackpot 3y ago
    That's interesting - does your career require any formal education? Or were you able to develop some crucial skill on your own? Can you share what is your career about and where you started and where are you now? For example - do you hire employees or are you a landlord now, or are you an employee?
    - fnordpiglet 3y ago
cbeach 3y ago
On the subject of correlation/causation, I once took a drug called Accutane to cure my teenage acne. Listed side effects included: "Mental health issues depression, psychosis, aggressive behaviour and suicide ideation and attempts" Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects. However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem. For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge. So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.
- ipaddr 3y ago
  It takes a lot including many suicides to get that side effect listed. You are lucky it didn't reach that point for you. With a little more time or repeated usage it probably would have got you as well.
- dan-robertson 3y ago
  Yeah a lot of the side effects you listed sound a bit like they could be within normal expectations for teenagers, or just slightly heightened. Reminds me of an SSRI that happened to also massively reduce caffeine metabolisation without anyone noticing, and loads of the known side effects were really just effects of caffeine overdose – insomnia, jitters, headaches, etc.
bdcravens 3y ago
Most of us, especially adults, are pretty much settled in with the state of our condition - we've had it our entire lives. Anecdotal, but many CF patients (including in online communities I'm a part of) have reported a lot of increased anxiety.
junon 3y ago
Just an anecdote. My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us). He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke. He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.
matthewtse 3y ago
(I left a previous comment as a similar sufferer of a lifelong genetic disease that was cured by a breakthrough medicine: https://news.ycombinator.com/item?id=37541222 https://news.ycombinator.com/item?id=37541222) Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before. A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.

therein 3y ago

Just an anecdotal experience so doesn't necessarily mean anything but the only person I knew that had CF had absolutely no anxiety from his condition. If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.

mason55 3y ago

> I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety? There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal. So it seems to be a bit of an open question and I'm sure an emotional one on both sides.

ipaddr 3y ago
Clinicians are always a day late and a dollar short. The evidence comes from these people reporting. These clinicians need a 50 million dollar grant to get that proof.
- TechnicalVault 3y ago
  If you've ever had to organise a scientific study you'll understand why. Privacy and ethics are important but they make recruitment of a large and representative sample for any medical study a nightmare. First you'll need to run your protocol past an ethics board and do back and forth until it's agreed. Once you have that done you'll send out an invite (often blind) in hopes of getting people who fit your study aims and you will get who you get. There are often costs associated with this. So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses. Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion. tldr; medical and scientific studies are hard if you want them to actually have any validity.
  - pas 3y ago
    wouldn't this side-effect become visible in Phase4 data? (and there should be at least some hints of this in the previous ones) so, what I'm trying to say is that for this particular drug we "just need to wait", no?
  - AdamN 3y ago
    It seems like we really need to move forward to 'indefinite/active studies'. I believe some researchers are trying to get onto this pattern but of course there are major privacy/quality of care concerns. By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).
    - 3y ago

vkou 3y ago

People generally get acclimated to the situation they are in. If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.

pfannkuchen 3y ago
You might even have more with 15M! It’s much harder to replace if you lose it.
fnordpiglet 3y ago
I grew up with a lot of money insecurity, was homeless for a while and started my career with nothing - one change of clothes and a floor to sleep on. I’ve since done very well for myself and have a considerable amount of net worth at this point and a lucrative forward for as long as I want to keep working at it. I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had. That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.
- TotalCrackpot 3y ago
  That's interesting - does your career require any formal education? Or were you able to develop some crucial skill on your own? Can you share what is your career about and where you started and where are you now? For example - do you hire employees or are you a landlord now, or are you an employee?
  - fnordpiglet 3y ago

cbeach 3y ago

On the subject of correlation/causation, I once took a drug called Accutane to cure my teenage acne. Listed side effects included: "Mental health issues depression, psychosis, aggressive behaviour and suicide ideation and attempts" Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects. However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem. For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge. So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.

ipaddr 3y ago
It takes a lot including many suicides to get that side effect listed. You are lucky it didn't reach that point for you. With a little more time or repeated usage it probably would have got you as well.
dan-robertson 3y ago
Yeah a lot of the side effects you listed sound a bit like they could be within normal expectations for teenagers, or just slightly heightened. Reminds me of an SSRI that happened to also massively reduce caffeine metabolisation without anyone noticing, and loads of the known side effects were really just effects of caffeine overdose – insomnia, jitters, headaches, etc.

bdcravens 3y ago

Most of us, especially adults, are pretty much settled in with the state of our condition - we've had it our entire lives. Anecdotal, but many CF patients (including in online communities I'm a part of) have reported a lot of increased anxiety.

junon 3y ago

Just an anecdote. My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us). He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke. He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.

matthewtse 3y ago

(I left a previous comment as a similar sufferer of a lifelong genetic disease that was cured by a breakthrough medicine: https://news.ycombinator.com/item?id=37541222 https://news.ycombinator.com/item?id=37541222) Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before. A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.