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

Depression runs in my family. Please be considerate in your replies here to me.

I think in US every available antidepressant has that 'suicidal thoughts' warning right at the top of the list yet antidepressants have been a very valuable tool for our family for young and old alike.

I do not believe that any causation has been determined for currently commonly prescribed medications. This is Reuters article reprinted at sciam does not show that at least. What GSK did hiding studies is reprehensible of course. Vulnerable families were hurt. The positive is the increased scrutiny now thanks to that.

My beliefs on the matter: Antidepressants are one tool, about 20% of dealing with the level of depression in my family. Sometimes the chemicals in our brains are just so out of whack no amount of therapy gets to us.

For an adult like me, I have had enough experiences (bad relationships, financial strain, health issues, legal problems, work stress, and so on) in my life to more easily put them in healthy context to what happens three years out say. I also remember how when I was younger that was impossible cause I lacked that experience. This is reflected by the rest of my family.

What I believe happens is the following: People with depression are already more likely to have thoughts of hurting themselves. There are some young people that will use manipulation to get what they want that also suffer from depression. 'You take away the only thing I like and I will hurt myself,' where that thing is not a healthy coping mechanism. So that thing gets taken away and the kid gets a psych-eval. The social worker evaluating everything decides this is a case of manipulation and the child is at an appropriate level of care. The problem is that some children have used manipulation but really do end-up hurting themselves after this since the other coping mechanisms they have in place at the time either get ignored or are insufficient.

Now my ire does not rest solely with GSK here. When I said the licensed state social worker evaluates everything, aspects come into that which should not for medical reasons but do for societal ones. One of those things have been what other options are available. People have been denied needed care based on there not being room in the programs (because of underfunding essentially), there not even being the appropriate program (for example intensive outpatient again often because of underfunding), or what insurance will pay. Thankfully that has not effected my nuclear family too much, but has affected others in my wider family that are unfortunate to live in other places or have worse insurance. That said, even to this day there are limits to mental health in my insurance program. Thankfully they are not not as onerous as they were in the past, but it does cause us stress to navigate it and not go over what is permitted.

The other thing is that simply you need a good team to work with you, a doctor and a therapist. There are those with mental health illnesses that are unlucky to not have good choices there. There are too many practitioners that are simply overworked and can't really offer the attention that is needed for proper care. They have known about this 'suicidal thoughts' danger, but they also see the benefits which nothing else offers. So they get into a routine of using one system for everyone as much as possible. But then because of time and insurance reasons there is not enough attention to tune it then as time goes on together with therapy. For example our insurance will only pay for a parent to consult with a therapist once a week for a child even in intensive outpatient care. So you have to find one willing to do that over the phone more often and not get paid for it essentially.

Well that was rambling, sorry, but somewhat therapeutic for me currently, thank you.

> (If you happen to be depressed, I can guarantee it gets better as you age, or with time.

This is a dangerous myth.

Suicide is a leading cause of death. Suicide is the leading cause of death for men aged between 20 and 49 in the UK. 12 men die by suicide each day in the UK (and about 3 or 4 women); one person dies by suicide every 12 minutes in the US.

> Hang in there.

Unfortunate phrasing, when "hanging, strangling, and suffocation" is the leading method of death by suicide, followed closely by poisoning.

This is an egregious violation on many levels. It highlights a massive gap in the clinical trials process (companies can stop trials without reporting negative results) that really should be addressed. I think everyone (outside of drug companies) can agree on that much.

I would like to say a few words on SSRIs (the class of drugs that Paxil is in) and their risks in general, because articles like these tend to cultivate strongly negative feelings toward SSRIs due to the deplorable drug company actions mentioned in this article. I don't blame people for mistrusting the drug companies after reading something like this. I also feel that SSRIs are prescribed too quickly and with too little extra guidance from doctors, although that trend is changing a bit as doctors become more educated.

But my biggest concern is that we're starting to see many people with severe depression who refuse to take SSRIs because they don't trust the drug companies and they've come to believe that their severe depression is still better than the side effects or risks of an SSRI, which couldn't be farther from the truth.

The bottom line is that SSRIs, while far from perfect, are still one of the most effective first-line treatments for severe depression that we have, and they do it with a side effect profile that is head-and-shoulders above previous generation anti-depressants.

Perhaps the biggest problem with SSRI treatment is the delayed onset of action. Unlike short-term rewarding drugs such as stimulants or opioids that may boost one's mood in the short term but quickly develop tolerance, SSRIs work through long-term adaptive changes. These changes are numerous, from increased BDNF and hippocampal growth to HPA axis normalization and restoration of brain connectivity back to a state that more closely matches that of non-depressed patients. However, the problem is that all of this happens as downstream effects of an alteration in how serotonin moves through the brain, which is very disruptive in the short-term while the brain adapts to the changes.

SSRI stands for selective serotonin reuptake inhibitor, which means that it inhibits the ability of serotonin-releasing neurons to take serotonin back up from the synapse after they release it. This doesn't "raise serotonin levels" as many describe it (unfortunately perhaps due to some awful SSRI marketing in the 90s and 00s) but rather alters the dynamics of how serotonin-based circuits operate. Serotonin will now spend more time in the synaptic cleft, activating post-synatpic serotonin receptors and synaptic transmission becomes a bit more smoothed out as the transmission takes longer to terminate via MAO deactivation of the serotonin or via uptake from the ~20% of uninhibited serotonin transporters.

Over time (4-8 weeks on average) the post-synaptic receptors adjust to the "new normal" levels of serotonin that they see in the synaptic space. This adjustment might even be key to some of the therapeutic effects of SSRIs, as some serotonin circuits may be too active in depressed or anxious patients, but the chronic SSRI administration quiets those receptors down, somewhat counter-intuitively. The big problem here is that until those receptors compensate, the patient may actually feel worse in the short-term. (Note that some patients actually feel substantially better during this phase, so please don't take this as a given). In the worst-case, depression or anxiety are actually worsened temporarily, combined with an increased energy due to the SSRI's activating effects. At the extreme worst-case scenario, this can lead to suicidal ideation, and for whatever reason this is more common in teenagers.

I wrote all of this out because the HN crowd tends to want to know how things work behind the scenes or under the hood when making decisions for themselves. My goal is not to suggest that everyone who experiences depression should be on SSRIs, because I actually feel that medication is probably best reserved as a first-line treatment for moderate to severe depression. Instead, my goal is to keep everyone informed such that they can work with their doctor to find the best treatment for themselves without unnecessarily fearing SSRIs due to these deplorable actions of drug companies a few years ago.

If you're feeling depressed, work with your doctor to find a solution. If you question your doctor's decision, see someone else. But it's important to explore all options if depression is taking a toll on your life, and if you choose to go the SSRI route then be aware that therapeutic effects are 4-8 weeks out, at least, and talk to your doctor right away if you're concerned.

-> http://www.alltrials.net/

and this topic: http://www.alltrials.net/news/new-research-on-old-data/

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BMJ Editorials: "Liberated trial data have enduring potential to benefit patients, prevent harm, and correct misleading research" : http://www.bmj.com/content/351/bmj.h4601

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BMJ "No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility" http://www.bmj.com/content/351/bmj.h4629

How can we really be sure that they're more efficacious than placebos (which can be quite efficacious) when we aren't allowed to see negative data generated during clinical trials? We have absolutely no aperture into the internal studies that weren't submitted as proof of the drug being effective. Sure, administering these drugs will make some patients report fewer negative symptoms-- typically the worst hit patients are helped the most, so it's definitely worth employing clinically despite the hangups. Effectiveness on target isn't a reason to stop asking critical questions and finding better alternatives. We know very well that long term use of antidepressants or other psychiatric medications has permanent consequences on brain structure and plasticity. There's always long term sexual dysfunction as well, sometimes permanently. I guess people can try to dismiss these side effects, but they're nearly always downplayed by the pharmas and up-played by the actual patients who are unhappy with their treatment.

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. You can't take measurements of 5-HT concentrations inside of a patient's brain, and similar measurements based off of mouse models are moonshots, even with the fancy math which is meant to allow a parallel to be drawn. Similarly, there's not an objective test for most of these psychiatric disorders unfortunately, making a remission hard to quantify.

The human aspect is also something to remember. The pharmas have a ton of money, and intend to make more money using products they have already developed. There is a huge incentive for them to hire people with credentials to say that their drugs are more effective than placebos, and generally effective. There is a huge incentive to cover up negative data and bad side effects. There is a huge incentive to keep things the way they are.

I'm going to read through the link you posted and maybe respond again more in depth later, it looks interesting and worthy of discussion.