Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

scientificamerican.com

Post reply on HN
Print view View original

71–80 of 93 posts

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#71

Post by andreyf »

acveilleux wrote: post #67
andreyf wrote: post #66

Earlier quoted context omitted.

One option: https://en.wikipedia.org/wiki/Contract_research_organization

How is that a solution? I worked for a CRO and contractually, all we did belonged to the client, including all publishing rights on all results.

Sorry for not expounding, that was indeed a bit opaque. I don't have first hand experience with the industry and so would appreciate any corrections to my understanding of it.

When research is done via contract between two companies, it can be more effectively regulated to prevent hiding or discarding of results. I imagine there are already laws in place saying a company can't hide research results like this and CROs make compliance more likely because they do not benefit from hiding bad results as pharmaceutical manufacturers do. I don't think publication rights are the important bit here, but compliance with rules about disclosure to the FDA.

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#73

Post by jgalt212 »

What blows my mind about these clinical trials is that the truth is always going to come out if the drug goes to market. And for big pharma, that's the goal--get the drug to market (and the largest market possible).

While you can hide bad results when n is small. i.e. just re-run the trial with another or smaller n. However, when n gets large as the drug comes to market, there is nowhere to hide. The negative effects will become obvious and compelling as the sample size grows.

How do they think they can hide this?

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#74

Post by existencebox »

derefr wrote: post #70
existencebox wrote: post #14

Earlier quoted context omitted.

What concerns me as much as the initial side effects is your last paragraph, and the sentiment surrounding it. Benzos have been known to have some additional significant neurological consequences in the long term, and have always felt to me like a rather large sledgehammer for the problems they often treat. As such, "your behavior-modifying drugs give you a side effect so we'll shove more powerful drugs in your face"…

> As such, "your behavior-modifying drugs give you a side effect so we'll shove more powerful drugs in your face" was an attitude that I've seen multiple times and NEVER to good effect. I don't see why that couldn't make perfect sense, though: someone can be neurochemically imbalanced along multiple axes, but one imbalance can mask the other. For example, if I have ADHD (for real) and depression, then that'll look li…

Let me give a (probably very leaky) programming analogy: You have one library, and it solves 1 class of problems. You use a second library on top of it to try and address some bits introduced by library 1. This may well move the core metric needle to get you what you want, but you will undoubtedly incur unforeseen interactions, and additional potential edge cases.

When you add the brain into the equation, it removes all of the (comparatively flawless) understanding we have of the system the libraries are running within, and then when you add benzos, one of your libraries is now an enraged bobcat.

In a perfect world, I'd agree with your statements. I do not think we have an effective enough understanding of either the compounds we're using, or the systems we're impacting, to be as laissez faire with cocktails as we often are.

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#75

Post by pessimizer »

Drug Patents Give Companies Like GlaxoSmithKline Incentive to Lie

Published: 15 July 2010

"A NYT editorial ( http://www.nytimes.com/2010/07/15/opinion/15thu1.html?ref=op... ) commented on evidence that the drug maker GlaxoSmithKline had concealed negative research findings on its diabetes drug Avandia:

"'The clearest lesson to emerge from the hearings and other recent revelations is that GlaxoSmithKline, the maker of Avandia, can’t be trusted to report adverse clinical results fairly. The company must be watched like a hawk as additional trials that it sponsors go forward.'

"Arghhhhhhhhhhhhhhhh! Doesn't the NYT believe in the profit motive and incentives? The patent system, by granting monopolies that raise prices several thousand percent above the cost of production, gives drug companies an enormous incentive to conceal negative research findings. As long as these perverse incentives exist, then we have to watch every drug company like a hawk.

"Maybe some wacko socialists think that drug companies will act for the public good and willingly forego vast profits, but those who believe on markets and economics know that drug companies will try to get away with anything they can get away with. One day maybe an iota of original thought will be allowed into public policy debates on the patent system, but we haven't gotten there yet."

http://www.cepr.net/blogs/beat-the-press/drug-patents-give-c...

-----

Pharmaceutical Company Invented Diseases, One of the Incentives Provided by Patent Monopolies

http://www.cepr.net/blogs/beat-the-press/pharmaceutical-comp...

Tufts Economist Documents Inefficiency of Patent System for Financing Drug Research

http://www.cepr.net/blogs/beat-the-press/tufts-economist-doc...

-----

Patent Monopolies and the Costs of Mismarketing Drugs

April 2015, Ravi Katari and Dean Baker

Abstract: "Patent monopolies have long been used as a mechanism for financing innovation and research. The logic is that the government awards a monopoly on a product or process for a limited period of time in order to reward innovation. However, in addition to providing incentives for innovation and research, patent monopolies also provide incentives for a wide-range of rent-seeking behaviors, many of which can have major social costs. This paper attempts to calculate one category of these costs for prescription drugs. It produces estimates of the costs associated with mismarketing drugs. The estimates are based on assessments of the costs in the form of increased morbidity and mortality associated with five prominent cases of mismarketing over the last two decades."

http://www.cepr.net/publications/reports/patent-monopolies-a...

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#76

Post by acveilleux »

andreyf wrote: post #71
acveilleux wrote: post #67

Earlier quoted context omitted.

How is that a solution? I worked for a CRO and contractually, all we did belonged to the client, including all publishing rights on all results.

Sorry for not expounding, that was indeed a bit opaque. I don't have first hand experience with the industry and so would appreciate any corrections to my understanding of it. When research is done via contract between two companies, it can be more effectively regulated to prevent hiding or discarding of results. I imagine there are already laws in place saying a company can't hide research results like this and CROs…

That's not how CROs work usually work. Effectively, as far as the FDA is concerned, the CRO does not exist as a distinct entity, it's an organic part of the sponsor (i.e.: the reporting pharma.)

The sole organization reporting to the FDA is the trial sponsor.

A CRO that felt like it could just tip off the FDA could soon find itself without further contracts.

In addition, in a properly blinded trial, most of the players (whether CRO, sponsor or site/treating physician) have no clue who's being treated or not. Nor do they know much more than they need to conduct their business.

The safety of a clinical trial is normally the job of a data monitoring committee or something similar. They are normally independent and empowered to monitor the result and, most importantly, unblinded so they can actually use stats taking treatment into account to spot actual anomalies. They report to and are paid for by the sponsor. The sponsor is legally required to act on the findings and adverse events are required to be reported to the FDA. At least that's the theory.

Gory details here: http://www.fda.gov/downloads/RegulatoryInformation/Guidances...

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#77

Post by ryanmarsh »

DanBC wrote: post #32

This study is more interesting. young people on certain anti-depressants are at higher risk of violence. We don't know which way causality runs. We don't see the effect in older people. http://journals.plos.org/plosmedicine/article?id=10.1371/jou... > These findings show an association between SSRIs and violent crime that varies by age group. They cannot, however, prove that taking SSRIs actually causes an increase i…

Sadly, this will not help my brother (or his dead friend). My brother is currently serving a 70 year prison sentence for murdering his best friend shortly after his Paxil dose was doubled. He was an early teen at the time.

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#78

Post by sunnid »

vonmoltke wrote: post #27
xlm1717 wrote: post #12

I've been seeing this pop up on all the major news outlets and science websites, but still have not seen one mention of the side effect that may be behind both increased risk of suicide and increased risk of violent behavior: akathisia. Akathisia is a side effect of antidepressants that causes an intense inner restlessness and inability to sit still. This can cause agonizing pain and terrible anxiety, and people can…

Worth noting that "antidepressant" is used rather loosely as a synonym for "SSRI". There are non-SSRI antidepressants on the market and this paper does not appear to cover those.

This is definitely worth noting. Wellbutrin, aka bupropion is a non-SSRI that some people I've known with depression have recommended. After discontinuing Celexa which is an SSRI, the whole experience was significant enough for me to handle my problems through cognitive behavioral therapy.

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#79

Post by throwaway98031 »

cryoshon wrote: post #60
throwaway98031 wrote: post #53

Earlier quoted context omitted.

> Then there's the academic problem: the monoamine hypothesis (the underlying theory behind the actions and use of SSRIs etc) is at best a crude approximation with precious little in vivo data to support ideas that are known to be inaccurate and incomplete. The monoamine hypothesis of depression (the idea that all depressions are directly attributable to negative alterations in monoamine dynamics) has been known to b…

An uber simplified version of the monoamine hypothesis is exactly how these drugs are marketed people today, and you know it-- just watch the TV commercials advertising SSRIs and it is impossible to avoid the conclusion that they are pitching the monoamine hypothesis as correct and understood to an ignorant public. I think it's fair to say researchers are still operating loosely within the framework of monoamine imba…

I'm not sure where you're getting your information from, but a lot of it is very incorrect and has a strong anti-pharma bias. For example:

> Paradoxically if they were stepping away from the monoamine hypothesis, they would produce polymonoamine regulatory drugs which would more subtly manipulate multiple monoamines in order to get the desired modulation of maloperating neural circuits, the target du jour.

The suggestion that pharmaceutical companies aren't exploring other pathways has never been more wrong, as we have quite a few very novel compounds in the pipeline that operate through very different pathways. Search for my other comment in this thread where I listed several of the other pathways and medications being explored.

Furthermore, I'm confused by your simultaneous dismissal of the monoamine hypothesis and insistence that "polymonoamine" drugs are the way to go, which isn't compatible with your assertion that the monoamine hypothesis is false. For what it's worth, there are several drugs in the pipeline that work through different combinations of monoaminergic pathways, but the most promising developments are actually in drugs that don't work through monoaminergic pathways at all (e.g. NSI-189, GABA-A5 antagonists, and so on.)

Re: Analysis of Antidepressant Paxil Finds Data on Teen Risk Was Held Back

#80

Post by MichaelGG »

refurb wrote: post #51

For all the condemnation of GSK, it appears that the "harm coding" changed from the original trial because the FDA changed the system they used. And was a major driver for why the AEs were captured in this study and not others. The other thing to keep in mind is that if this was a pivotal trial study, the FDA had the complete data set yet failed to recognize the increase in suicidal ideation as well.

The FDA really seems to have a bad rep. See, for instance, Ranbaxy: http://fortune.com/2013/05/15/dirty-medicine/

They were faking results and running terrible QC, to the point of shipping glass in pills. The FDA was very slow to fine them, and then only closed specific sites. It's obvious this company was rotten to the core, and is now part of Sun Pharma. FDA's done a bit more since then, but they should have issued a full ban and then started to whitelist things bit by bit. Local health inspectors come down harder.

It creates other effects, too. By looking bad in some cases, people stop trusting the FDA. They then decide that things like sucralose are harmful "because you can't trust the FDA", and instead consume large amounts of sugar (it's natural!).

Post reply on HN