Re: Weekend Longread

1

It's a super-long read, but worth it if you're in the mood for outrage.


Posted by: J, Robot | Link to this comment | 11- 7-15 4:58 PM
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I should be outraged, but mostly I'm relieved that I was never funded by them.


Posted by: Moby Hick | Link to this comment | 11- 7-15 5:09 PM
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At first I thought this was about Kai Risperdal, host of NPR's Marketplace.


Posted by: Roberto Tigre | Link to this comment | 11- 7-15 8:03 PM
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Really compelling reading.


Posted by: CharleyCarp | Link to this comment | 11- 8-15 1:30 AM
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It's also confirmed my decision to never take an anti-psychotic. Everyone know who has gone on one has gained 30-60 pounds that they haven't been able to lose.


Posted by: J, Robot | Link to this comment | 11- 8-15 11:46 AM
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That's also what happened to everybody I know who didn't take an antipsychotic.


Posted by: Moby Hick | Link to this comment | 11- 8-15 11:57 AM
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I was briefly on Risperdal at 16 when they were throwing every possible drug at me to see what would stick, though I think only Zyprexa, which I took for maybe a year, gave me weight-gain side effects, and some of that was surely due to ceasing to be anorexic. A child in my care had a few months of Risperdal too. This is exactly the kind of use singled out in the study, paid for by state insurance for a minor who doesn't have psychotic symptoms and if I'd had the right to make medical choices as a parent I would have refused it. But I was just the foster parent and did trust that doctor, who had other good advice about why some drugs might work better than others for this child, and it certainly seemed to change things overnight and do exactly what was needed most, stabilize a child who needed to be calm enough to learn coping skills that would make life in the post-medication era manageable. That's exactly how it worked, but I've always wondered how marketing and so on played into it. (I'm quite sure I've seen different trends in mental health diagnoses for kids in my care than the rest of you would have gotten showing up with your biological children and private insurance and needing help or support.)


Posted by: Thorn | Link to this comment | 11- 8-15 7:19 PM
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risperdal SUCKS. it totally blows and makes you feel terrible. I mean, psychosis is also very bad, but. I was able to lose the weight by having a manic episode, IIRC. worst diet ever, though.


Posted by: alameida | Link to this comment | 11- 8-15 10:58 PM
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There's quite a disconnect between people who work on the science side and the marketing/sales side, fortunately I've almost never interacted with the latter. People on the science side are generally aware that sales pays their salaries (and if they're at a public company their options/retirement) but they're also paranoid about any hint of data that suggests a side-effect: cardiac (hERG), carcinogens, liver toxicity, potential to interact with other drugs. Sure, part of that is that it limits the market if there's a side effect, but also no one wants to be the person who said don't worry about some piece of data and ends up killing people. Managers who make decisions are possibly overly risk averse about these things- for example there's a test for whether a drug causes mutations that could cause cancer, although there are examples of marketed drugs that fail this test but also never cause any mutations in patients so it's not 100% predictive. But if your potential drug fails the test, too bad, end of the line, even though there are more expensive tests that can tease out the likelihood of a false positive.
(Also your tolerance for side effects is tied to the disease you're working on- any significant side effect is a big no-no in long term treatments like psychiatry, diabetes, cardiovascular, but you'll throw just about anything at someone who has stage IV pancreatic cancer.)


Posted by: SP | Link to this comment | 11- 8-15 11:19 PM
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Wait. There are huge side effects to a great many drugs for psychiatric indications (e.g. tardive dyskinesia, liver blowing up, death by fancy cheese). The calculation for the utility and cost effectiveness of newer medications is pretty explicit about comparing to that.


Posted by: Moby Hick | Link to this comment | 11- 9-15 5:00 AM
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Yeah psychiatry stood out to me too in that list. Even the nicest, calmest safest psychiatric drugs have a tendency to occasionally just sort of blow up on people unpredictably (and rarely, yes, but often enough that we know they do it and usually what it looks like when they do it as well). And the ones that drug companies haven't successfully sold to doctors as "they're basically just tic tacs only your patients will feel great and not have any troubles in life!" can be absolutely terrifying.


Posted by: MHPH | Link to this comment | 11- 9-15 6:21 AM
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It was pretty predictable and terrifying.


Posted by: Pure Equity | Link to this comment | 11- 9-15 9:05 AM
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10, 11: Isn't there a group of anti-depressants? Anti-anxiety meds? that's not all that bad while you're taking them, but are very likely to have really very extreme side effects when you stop?

I generally associate (with no non-anecdotal knowledge) psyche meds with really disproportionate-sounding side effects.


Posted by: LizardBreath | Link to this comment | 11- 9-15 9:30 AM
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That's same meds as have the death-cheese effect.


Posted by: Moby Hick | Link to this comment | 11- 9-15 9:33 AM
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The tricyclic antidepressants, to be more helpful. I don't think they get used much anymore.


Posted by: Moby Hick | Link to this comment | 11- 9-15 9:34 AM
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15 is wrong. There are two different, but now rarely used, classes. One that won't let you eat cheese and one that has the potential for big problems on discontinuation.


Posted by: Moby Hick | Link to this comment | 11- 9-15 9:39 AM
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So you have to eat cheese continuously forever?


Posted by: heebie-geebie | Link to this comment | 11- 9-15 9:40 AM
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Consult your doctor or wikipedia.


Posted by: Moby Hick | Link to this comment | 11- 9-15 9:41 AM
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Anyway, I think the bigger point is that if you had a bunch of doctors saying the atypical antipsychotics were safe because they were comparing it to thorazine and/or institutionalization, then marketing could have run with the "safe" label into new markets like kids where you would hope that a different risk assessment applied. I'm not going to look up that story because I'm not at all sure what I won't find is that kids were getting whole bunches of thorazine before they started to get whole bunches of the newer meds.


Posted by: Moby Hick | Link to this comment | 11- 9-15 9:46 AM
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Yeah, when I was getting all the prescriptions in the world, one of them gave me Tardive dyskinesia (may have been Risperdal, actually, but who can remember?) and that was awful. Most of the atypicals made me shake so hard I couldn't write or sometimes walk, I guess technically Parkinsonian tremors There's a lot of bad stuff out there that someone who's susceptible to side effects can run across, and that on top of being so depressed you seem to need strong medication is not a great outcome.


Posted by: Thorn | Link to this comment | 11- 9-15 9:53 AM
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19: "Compared to DNP, our new diet pill is safe."


Posted by: AcademicLurker | Link to this comment | 11- 9-15 10:01 AM
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I think most to all of them have "discontinuation effects"* but some of them are more severe than others. For a lot of them though it's mostly an effect of the drug's half life. (Prozac has an absurd nine day half life and so it lets you down easily; effexor and paxil have ones measurable in hours and are infamous for being horrible.

Tricyclic anti-depressants aren't really any worse than SSRIs (and the related SNRIs) from what I know, which isn't saying too much. They're harder on you when you're taking them though. MAOI inhibitors are the ones where you die if you eat anything with too much tyramine (fermented foods; old foods; etc.). They block the bits of the brain that break down tyramine and so you very very quickly have way, way too much and your bloodpressure goes up to stroketastic levels. MAOIs do still have discontinuation symptoms - mostly the same ones as the others.**

The anti-psychotics come with their own magical little phenomenon though which is that they both cause tardive dyskinesia and suppress it. So coming off them can result in it showing up and not going away.

*This term courtesy of pharmaceutical companies who, with I guess some justification, wanted to distinguish them from "withdrawal effects" which come along with an experienced need to take the drug some more (for reasons other than making the other stuff go away). It's a valuable distinction, but probably not one that most people associate with them.

**e.g., 'Agitation ' Irritability ' Pressured speech ' Insomnia and nightmares ' Visual, olfactory, and tactile hallucinations ' Feelings of disorientation to time and place ' Paranoia ' Aggressiveness ' Slurred speech ' Myoclonic jerks (sudden spasm of muscles) ' Clonus (rhythmical contraction of muscle in response to a suddenly applied and then sustained stretch stimulus) ' Ataxia (unsteady gait and balance) ' Athetosis (a writhing involuntary movement especially affecting the hands, face and tongue) ' Catatonia (a state in which an individual becomes mute or stuporous or adopts unusual postures) ' Electric shock feelings".


Posted by: MHPH | Link to this comment | 11- 9-15 10:35 AM
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19 is right though. A lot of trouble showed up when pharmaceutical companies started touting things (accurately*) as 'safe anti-depressants' or whatever and a lot of doctors, especially GPs and other non-specialists who, oddly, are the ones prescribing a lot of them, interpreted that as "safe for a prescription medication" as opposed to "safe for a prescription psychiatric medication". And those are two very different things, as it turns out.

*for the most part, not necessarily with the atypicals though they seemed that way at first. With more data thorazine actually doesn't look that bad anymore.


Posted by: MHPH | Link to this comment | 11- 9-15 10:37 AM
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It's very well written and held my attention much longer than most long reads on the web.


Posted by: Mooseking | Link to this comment | 11- 9-15 10:55 AM
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Well shit I have an appointment this afternoon to think about trying an SSRI or related.


Posted by: FDR | Link to this comment | 11- 9-15 11:09 AM
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If it's with a specialist you're probably safe-ish. If it's with a GP maybe be more cautious and spend some time on this website double checking things, or if they think it's worth it then make an appointment with a specialist.

For a lot of people the SSRIs or related first try drugs aren't that bad at all. It's more that there's a subset of people for whom they are bad, and then an even smaller subset for whom they're dramatically awful. And it's hard to know ahead of time which group a person falls into* so it's kind of a gamble, especially at first. Which, really, is just to say that they're like any other prescription medication only, maybe, a little more. The 'no cheese' or hideous movement disorders** ones aren't usually something you're going to get on the first or second go around.

*Are you bipolar? SSRIs are probably not a good idea - better to start with something else.
**Except when one of the usually benign ones does this because, I dunno, brains are like that. It's really rare, though, and when they do the chances of it being tardive or not just going away immediately when you stop are absurdly, vanishingly, 'I think I saw a case study once about this drug that millions and millions of people take where it kind of looked like maybe it had happened' level rare.


Posted by: MHPH | Link to this comment | 11- 9-15 11:27 AM
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Are you bipolar?

Re: good pediatric psych, part of the issue he cited was about genetic predisposition to bipolar disorder whether you have it or not, so if you have a parent who does it's worth bringing it up. Putting a definitely-not-qualifying-for-bipolar-diagnosis child on antidepressants appropriate for someone with bipolar disorder made a huge difference the two time I personally saw it happen. But I'm not a doctor or anything close.


Posted by: Thorn | Link to this comment | 11- 9-15 11:33 AM
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Been seeing psychologist, after ~7 sessions he referred back to GP with some recommendations. He did mention bipolar problem with SSRI but not an issue. Might try Prozac or Wellbutrin. Anxiety and depression in some amount.


Posted by: FDR | Link to this comment | 11- 9-15 11:44 AM
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If it is a GP I would definitely spend some time reading around beforehand, but mostly because GPs have a lot of stuff to keep up on and often you'll find them picking a favorite drug and just sort of sticking with it to keep things easier for them, at least when the general differences are relatively low. So, for example, Prozac is the best known SSRI, but escitalopram is a cleaner, faster acting and (somewhat, probably) more effective one (the variation isn't too large but there is some between SSRIs). I mean, if you don't want to see a specialist and the GP doesn't want to work with one SSRI over another then whatever, it's not a huge deal. But...


Posted by: MHPH | Link to this comment | 11- 9-15 11:57 AM
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often you'll find them picking a favorite drug and just sort of sticking with it

To be fair, Prednisone works for lots of things.


Posted by: Moby Hick | Link to this comment | 11- 9-15 11:59 AM
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genetic predisposition to bipolar disorder whether you have it or not, so if you have a parent who does it's worth bringing it up

Oh hey, this seems like a good time to ask: MIL has a suite of mental health problems (mostly anxiety/depression/OCD stuff) and a general history of mental illness in her family. AB has no such issues, and there are none in my family history. So my question is, when would it make sense to look at the kids for symptoms? Iris has some of MIL's tendencies wrt initiative*, but no sign of it as a deeper issue. But she's also just 11, and I imagine that this sort of thing tends to hit during adolescence and early adulthood. But of course adolescents tend toward moodiness and melancholy, so it seems like it would be easy to misdiagnose, or miss diagnose.

*that is, cleaning the room is impossible, because the task is so vast and daunting, so you sit for hours doing nothing but feeling hopeless. Iris only has bits of this, and she loves her new school so much that she's shown a ton of initiative on projects and such, so it's not too worrisome, but any tendencies towards MIL-like are alarming.


Posted by: JRoth | Link to this comment | 11- 9-15 12:52 PM
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You know, it might make a lot of sense for state medical boards to require written and signed disclosures for off label uses of anything requiring a prescription. Annoying for the docs, sure, but make that the playing field, and all the expectations that went into the marketing (and probably actually the development) of Risp get changed considerably.

(I was peripheral to a case 20 years ago or so where it was said that an off label use of the product was the standard of care.)


Posted by: CharleyCarp | Link to this comment | 11- 9-15 1:37 PM
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That's not exactly rare. For any condition that isn't common, pharma isn't going to run those kinds of studies when they come out with a new drug. And if the drug is already off-patent, you'd need public money to run that stuff. That's still not going to happen in any kind of a hurry, even for a common condition, if there is already a consensus and there is nobody pushing a new drug.

And using medicine tested only in adults on children seems very problematic, but it turns out that running tests on children is sort of its own ethical conundrum.


Posted by: Moby Hick | Link to this comment | 11- 9-15 2:01 PM
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Heck, even for relatively common conditions where the evidence is more than anecdotal the prescription could easily be off label. Going through the whole FDA approval process is pretty complicated, after all, and sometimes it's easier just to publicize a whole bunch of studies* showing that something really works well for something or other and let the Doctors figure it out. Controlled release Paxil and Paxil have three approved uses in common, and about four that aren't (Controlled release Paxil is also approved for the infamously oh-come-on PMDD***, and Paxil straight up isn't but is approved for OCD, GAD, and PTSD**** which the controlled release version isn't). I don't know that there's any reason to think that somehow one of them fails at doing stuff the other one can do, though.

*Which they may or may not have done themselves and which they may or may not be accurately describing, depending on how evil they're feeling at the moment.
**You can miss a lot more doses without serious consequences because of the half life. That's it.
***Premenstrual Dysphoric Disorder.
****GAD is General Anxiety Disorder, the others are obvious.


Posted by: MHPH | Link to this comment | 11- 9-15 2:59 PM
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Moby, did you read the whole article?


Posted by: CharleyCarp | Link to this comment | 11- 9-15 2:59 PM
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The J&J trial strategy sure didn't seem very well thought through.


Posted by: CharleyCarp | Link to this comment | 11- 9-15 3:01 PM
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I didn't read the article. It was really long.


Posted by: Moby Hick | Link to this comment | 11- 9-15 3:03 PM
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The strategy for Risp required a whole lot of off label use, because the label was so narrow. The FDA kept not letting them have what they wanted on the label, telling them the studies didn't support what they wanted. It wasn't so much an issue of studies not being done, but of them not showing the results that would justify the labeling.

But they went ahead promoting off label use anyway.


Posted by: CharleyCarp | Link to this comment | 11- 9-15 3:11 PM
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I'm not suggesting in 32 that off label prescription be prohibited. Just that docs and patients explicitly face up to the fact that it's off label.


Posted by: CharleyCarp | Link to this comment | 11- 9-15 3:13 PM
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And that's a problem, but I think it's a smaller problem that trying to shut down or stigmatize all off-label use. Because I have read submissions to the FDA.


Posted by: Moby Hick | Link to this comment | 11- 9-15 3:17 PM
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I should have refreshed there before 40. Sorry.


Posted by: Moby Hick | Link to this comment | 11- 9-15 3:18 PM
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But, when you are talking about an antipsychotic or any medication given in vulnerable populations (e.g. children, the institutionalized elderly, people with active psychosis), the problem is that the patient either can't face-up explicitly to anything or is under an a great deal of pressure for non-clinical factors (e.g. "Take this or you'll never get out the hospital", "Give this to grandma or we'll have to kick her out of the only care home you can afford").


Posted by: Moby Hick | Link to this comment | 11- 9-15 3:21 PM
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11 yr old unable to face cleaning her room seems to me so far from a sign of incipient mental health issues as to constitute perhaps a healthy disposition to do pretty much anything else!


Posted by: dairy queen | Link to this comment | 11- 9-15 3:37 PM
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I did read the short article from the NYT.


Posted by: Moby Hick | Link to this comment | 11- 9-15 3:46 PM
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45

Let me recommend a treatment for short attention spans.


Posted by: SP | Link to this comment | 11- 9-15 4:44 PM
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46

I don't want amphetamines.


Posted by: Moby Hick | Link to this comment | 11- 9-15 4:47 PM
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47

So, Jos/eph B. still has a job at that hospital (#1! But only #2 in psych), and he advises the primary care leadership on how to manage depression in primary care.

It kind of makes me want to puke.


Posted by: NE City Resident | Link to this comment | 11- 9-15 5:01 PM
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Trying celexa. GP seemed knowledgeable about spectrum of SSRIs and other classes, relative side effects, etc.


Posted by: FDR | Link to this comment | 11- 9-15 6:03 PM
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Be careful about taking the drug that has its name on your doctor's pen.


Posted by: Moby Hick | Link to this comment | 11- 9-15 6:19 PM
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50

Do you need a prescription for Dixon Ticonderoga?


Posted by: fake accent | Link to this comment | 11- 9-15 6:30 PM
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Only cheap drugs get their name put on pencils.


Posted by: Moby Hick | Link to this comment | 11- 9-15 6:39 PM
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48 - That sounds like a good first choice when depression+anxiety, though it might be worth asking them about switching to escitalopram at some point because it's probably* cleaner with the same benefits. But depending on your health insurance it could also be more expensive for you, I don't know. I've generally had fancy student and/or poor person health insurance where prescription co-pays were limited enough that the two would have been the same price. Also it's one of the most recent ones so it hasn't been generic for as long.

*"Probably" because there are some questions about evergreening with those two drugs. But I think that there is some decent evidence to the contrary. Celexa -> citalopram, and escitalopram (lexapro) is just the (S)-stereoisomer of citalopram (clearly someone got a little lazy with the naming). Supposedly that's the part of citalopram that was doing the work already, so it just means a cleaner drug and a lower dosage. Since it's that closely related "switching" could probably just mean that in a literal sense.


Posted by: MHPH | Link to this comment | 11- 9-15 8:02 PM
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36: Reading about the various legal strategies was one of the things that made the article so fascinating. I see a ton of the commercials mentioned in the article ("Have you or your loved ones been diagnosed with..."), so it was also interesting to read about that strategy in particular.

48: This is anecdotal, but I don't recall Celexa having any major side effects for me at all. Really, the only psychiatric drug I've had a bad response to has been Welbutrin, though I've avoided the anti-psychotics.


Posted by: J, Robot | Link to this comment | 11-10-15 8:57 AM
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Some of the early studies on antipsychotics were for using on aggressive children with severe developmental disabilities. They never went forward with that one, but it is how they're often used.


Posted by: Bostoniangirl | Link to this comment | 11-10-15 11:06 AM
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