Bad science: The serotonin theory of depression

[Ismene]

Perhaps we need to look for another theory to explain the alleged connection between E and depression...

Over the past few decades, we have been subjected to a relentless medicalisation of everyday life by people who want to sell us sciencey solutions. Quacks from the $56bn (£28.26bn) international food supplement industry want you to believe that intelligence needs fish oil, and that obesity is just your body's way of crying out for their chromium pills ("to help balance sugar metabolism").

Similarly, quacks from the $600bn pharma industry sell the idea that depression is caused by low serotonin levels in the brain, and so you need drugs which raise the serotonin levels in your brain: you need SSRI antidepressants, which are "selective serotonin reuptake inhibitors".

That's the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I'm not giving that lecture here, but as a brief illustration, there is a drug called tianeptine - a selective serotonin reuptake enhancer, not an inhibitor - and yet research shows this drug is a pretty effective treatment for depression too.

Meanwhile, in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home.

The serotonin hypothesis will always be a winner in popular culture, even when it has flailed in academia, because it speaks to us of a simple, abrogating explanation, and plays into our notions of a crudely dualistic world where there can only be weak people, or uncontrollable, external, molecular pressures.

http://www.guardian.co.uk/commentisfree/2008/jan/26/badscience

 

[Ismene]

Jury Trials In 2008 Expected To Expose SSRI Maker's Dirty Secrets

The blockbuster sales figures for the new generation of selective serotonin reuptake inhibitor antidepressants (SSRI's), which have resulted from their promotion for so many unapproved uses, represents the most profitable off-label marketing coup in the history of modern medicine. Sales total about $21 billion a year, according to IMS Health.

The standard line used to sell SSRI's is that mental illnesses are caused by a chemical imbalance in the brain and that SSRI's correct the imbalance. The Lexapro website even states: "Antidepressant medicines relieve the symptoms of depression by restoring chemical imbalances in the brain."

However, "Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature," in the November 8, 2005, PLoS Journal, by Jeffrey Lacasse, a visiting lecturer at the Florida State University, and Jonathan Leo, an Associate Professor of Neuroanatomy at Lincoln Memorial University, reports that, "there is not a single peer-reviewed article that can be accurately cited to directly support claims of serotonin deficiency in any mental disorder, while there are many articles that present counterevidence."

In their most recent paper titled, "The Media and the Chemical Imbalance Theory of Depression," appearing in the February 2008 issue of Society, Mr Lacasse and Mr Leo report that, "In spite of the enormous amount of money and time that has been spent in the quest to confirm the chemical imbalance theory, direct proof has never materialized."

In fact, they advise that the Diagnostic and Statistical Manual of Mental Disorders, which almost all psychiatrists use to diagnose and treat their patients, clearly states that the cause of depression and anxiety is unknown.

Even when prescribed for their intended purpose in treating depression, many experts say SSRI's are ineffective. One of the world's most famous psychopharmacologists, Dr David Healy, author of "The Antidepressant Era," and "Let Them Eat Prozac," says that an overall review of the published clinical trial data on the new antidepressants reveals a 10% difference in the way people respond to the drugs verses a placebo.

He reports that 50% of patients taking the antidepressants showed some improvement and 40% of people taking a placebo showed improvement. And when the data from the unpublished clinical trials are added in, 45% of patients taking a placebo showed improvement.

The author of "Surviving America's Depression Epidemic," Dr Bruce Levine also says "legitimate science shows that these antidepressants are no more helpful for depression than a placebo or no treatment at all."

However, most prescribing doctors have never heard about this 5% or 10% efficacy statistic, which researchers have referred to as the “dirty little secret,” because many of the studies that revealed the “secret” remained hidden for years.

http://www.scoop.co.nz/stories/HL0801/S00197.htm

 

[SmokingMan]

Now you are starting to get through some of the bs put out by Big Pharma. They don't care about being scientific or helping humanity through accurate research into our brain chemistry.
They only care about making more money. Making all the money they possibly can by selling us "a cure" for whatever ails us. My personal favorite is the drugs being marketed for "restless leg syndrome".
Where are the drugs for curing people of being uncaring money-grubbing assholes?!?!

You should watch the documentary "Selling Sickness" to see how little these "medicines" are researched and to see how the terrible effects is being covered up. This one is also available on torrent trackers, I believe.

 

[Infinite Jest]

As an aside, if we're discussing SSRIs and depression and so on, that should probably go in Healthy Living. We should probably keep this discussion focused on MDMA and serotonin (as Ismene alludes to in the first sentence).

So I'll respond to that

Ismene: we know that MDMA affects serotonin. We have dozens, probably hundreds of animal studies: give an animal MDMA, cut it open, look at the serotonin receptors. They're altered.

We also know that MDMA increases the brain's release of serotonin.

We also have a heck of a lot of evidence for a link between heavy MDMA use and depression - both scientific studies and self-reported, anecdotal data.

So what's the alternate hypothesis? If not serotonin, where's the explanation?

[Incidentally the articles you cite: the first one merely points out some examples of bad science writing. It doesn't make any effort to look at the underlying science. The second one, well it's published on Scoop: anyone can publish anything on Scoop - it's a press release site that publishes anything. I could spend half an hour writing a refutation to that article, and get it published, but it wouldn't be good evidence. I think you need to point to more credible sources; articles from peer-reviewed journals, as I've suggested to you before .

And getting off-topic: I do agree that pharma companies are probably over-selling the benefits of SSRIs (and other meds): but even so, SSRIs work better than placebos, even according to those critical articles you cite. That means they work! Not for everyone, but for some people. And we know different SSRIs hit different serotonin receptors. Possibly with better understanding of depression, we will realise which patients need which SSRI, and then see improvement (I wonder what would happen if you compared someone who only got placebo with someone who was tried on several different SSRIs, if the first one didn't work? I bet you'd see a higher success rate...)]

 

[Groovy guru]

Making all the money they possibly can by selling us "a cure" for whatever ails us. My personal favorite is the drugs being marketed for "restless leg syndrome".
Where are the drugs for curing people of being uncaring money-grubbing assholes?!?!

Not to get off topic, and as much as I share your disgust for big pharma, to be fair those drugs (dopamine agonists Requip and Mirapex) were initially developed to treat Parkinson's. The "restless leg" syndrome is just so that they can sell them to more people and make more money but they weren't developed for that purpose. This market is especially important as Requip is going off patent soon and they want to try to renew patents with "novel" time-release formulations, one of which is targeted towards "restless leg". Again to be fair, such time-release formulations are better for PD as well...

 

[Ismene]

Serotonin anti-depressants "useless"

[Incidentally the articles you cite: the first one merely points out some examples of bad science writing. It doesn't make any effort to look at the underlying science. The second one, well it's published on Scoop: anyone can publish anything on Scoop - it's a press release site that publishes anything. I could spend half an hour writing a refutation to that article, and get it published, but it wouldn't be good evidence. I think you need to point to more credible sources; articles from peer-reviewed journals, as I've suggested to you before .

And getting off-topic: I do agree that pharma companies are probably over-selling the benefits of SSRIs (and other meds): but even so, SSRIs work better than placebos, even according to those critical articles you cite. That means they work! Not for everyone, but for some people. And we know different SSRIs hit different serotonin receptors. Possibly with better understanding of depression, we will realise which patients need which SSRI, and then see improvement (I wonder what would happen if you compared someone who only got placebo with someone who was tried on several different SSRIs, if the first one didn't work? I bet you'd see a higher success rate...)]

Hate to say "I told you so.." Infinite but..."I told you so..."

Anti-depressants 'a waste of time'

New-generation anti-depressants are largely a waste of time, research suggests.

A review of clinical trials found they worked no better than a dummy pill for mildly-depressed patients and for most people suffering severe depression. Even trials suggesting benefit for severely-depressed people did not provide evidence of clear clinical benefit, researchers said.

Dr Tim Kendall, deputy director of the Royal College of Psychiatrists Research Unit, said the findings were "fantastically important".

A group of experts, led by Professor Irving Kirsch, from the Department of Psychology at the University of Hull, analysed 47 clinical trials using data released under Freedom of Information rules by the US Food and Drug Administration (FDA).

The researchers looked at four commonly-used anti-depressants and the clinical trials submitted to gain licensing approval. They included anti-depressants regularly prescribed in the UK, including fluoxetine (Prozac), venlafaxine (Efexor) and paroxetine (Seroxat).

They found little evidence of benefit when analysing both unpublished and published data from the drug companies. Furthermore, the seemingly good results for very severely-depressed patients came from the fact that a patient's response to the dummy pill (placebo) decreased rather than any notable increase in their response to antidepressants.

"Drug-placebo differences in anti-depressant efficacy increase as a function of baseline severity, but are relatively small even for severely-depressed patients," the researchers said.

"The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely-depressed patients, rather than to increased responsiveness to medication."

The researchers said their study was one of the most thorough investigations into the efficacy of new generation anti-depressants, known as Selective Serotonin Reuptake Inhibitors (SSRIs).

The researchers concluded: "We find that the overall effect of new generation anti-depressant medications is below recommended criteria for clinical significance." Professor Kirsch said: "The difference in improvement between patients taking placebos and patients taking anti-depressants is not very great. This means that depressed people can improve without chemical treatments."

http://ukpress.google.com/article/ALeqM5gVJDAnYziRdUKG2eGWus-IPauPlA

 

[Infinite Jest]

Interesting.

I read an article 15 years ago by someone who'd successfully carried out cold fusion. Yet today we still don't have cold fusion reactors. No one could replicate his research.

Science requires replicability. If someone replicates this (actually, if several people replicate it) then that will be interesting. Till then, all you've got is one article in a fairly low-ranked journal. (Actually, you haven't even got that, you've got a newspaper article about the journal article. And we all know how accurate newspaper reporting of science is).

More seriously, the newspaper article doesn't seem to make much sense. Let's break down the reported results:

mildly depressed patients improve with either placebo or SSRI
severely depressed people improve with SSRI, but not with placebo.

Conclusion: SSRIs don't work.

Wouldn't it be just as possible that the mildly depressed people didn't need treatment at all, and therefore responded to any treatment - real or placebo? Whereas the severely depressed people did need treatment, and only responded when they received real treatment.

I'm also not impressed with the final sentence you quote - it's a total straw man - "depressed people can improve without chemical treatments". No one has ever denied this.

 

[Ismene]

Science requires replicability. If someone replicates this

I think they were reviewing the results of all the studies the pharma corps carried out - the pharma corps only released the ones that suggested SSRI's worked. The implication being there was never any evidence SSRI's worked in the first place.

mildly depressed patients improve with either placebo or SSRI
severely depressed people improve with SSRI, but not with placebo.

I don't think they say it's the SSRI that's making the difference tho.

 

[ifonly]

from everything ive read about seratonin ( a lot )

i can assuredly say that, in my opinion, my use of extasy has caused low seratonin levels which i have never been able to re-establish, even after nearly a year of never touching mdma.

 

[serotoninstorm]

Any opposition if I move this to healthy living?

 

[Infinite Jest]

^
Well, Ismene was posting it here because he's using it as evidence for his argument that MDMA doesn't effect serotonin (if I understand correctly). Also, there's already a thread in HL. I'm inclined to leave it here, but over to you - Ismene's opinion would obviously be welcome at this point.

Ismene, I owe you a good reply on this one having seen some more coverage. Will try to do so today

 

[Ismene]

As Infinite says I'm posting it here because you read a lot of E users say "E causes depression because it affects serotonin levels - and everyone knows low serotonin levels cause depression, that's why we all take SSRI's isn't it...". Most of them seem to have bought into the serotonin theory of depression hook, line and sinker.

When really the only reason people take SSRI's is because pharma corporations can make an awful lot of money from selling them.

At the risk of raising Infinite's eyebrow with my favourite quote....ahem...

"The serotonin theory of depression has about as much evidence as the masturbation theory of insanity"

 

[edarrin]

We also know that MDMA increases the brain's release of serotonin.

We also have a heck of a lot of evidence for a link between heavy MDMA use and depression - both scientific studies and self-reported, anecdotal data.

So what's the alternate hypothesis? If not serotonin, where's the explanation?

The hypothosis is it depletes serotonin thereby causing depression due to depletion of this chemical, especialy in different areas of the brain.

MDMA causes the release of a lot more than serotonin. I would think it is related to a general loss of excitatory nureotransmitters of all kinds. Just like in the old days for me, going on a speed run. you feel pretty 'out of sorts' for a few days afterwards. It's not a new phenonenom, although the e generation seems to have taken credit for the effect

Rest, good nutrition and not to use too frequently and one should be relatively OK, not to say there might not be some 'payback' in the long term.

Areas like normal sleep patterns, brain function (concentration,planning and abstract reasoning can be effected..although I'm not confinced that 80-90% can"t be restored with abstainence.

I used various chemicals for 18 years then managed to get cleaned up 100%. I went back to school and now have a relatively good job. Point being I finished 2nd in the class which is pretty good even if it's patting myself on the back%) which would indicate to me that I still had most of my faculties. It took a good year to start feeling a lot better, sleeping well , energy level and motivation. Also regained an abilty to obtain pleasure from normal things as well. In short I pretty much recover.

Fast forward about 12 years. i get injured. I have surgery and chronic pain afterwards. I end up addicted to opiates...not completely against my free will...and am now struggling to stop. Problem now is I have a bonfide need for them but find it very difficult/impossible to not abuse them. I have enough around i short distance to use H which I have een doing and saving my pharms. Now I'm going to try and stop the H and just use my Rx. I get enough that I can go on a week long binge and still have enough to slowly taper back down and then maintain at prescribed dose for the most part. It is hard tapering down aftr those H and hydromorphone binges.

 

[Doc X]

Interesting debate - keep it here and focused

Hi All, in my view there is, and has been, alternative explanation(s) to depression "melancholia" for some time. In psychoanalysis depression is compared to mourning (e.g. the grief experienced through loss of a loved one). In the various theories of depression theoretical emphasis is placed upon the interplay between the ego, aggression and superego ('you conscience'). Shame, guilt, and sadness being three of the primary constitutive affects which overwhelm the ego (I) in these states.

Much of modern psychology and psychiatry has moved away from looking at the soul (psyche) and has moved to a universalistic neurological/physiological explanations for much of human behaviour. The gene has come to replace God as the "explanation" for everything. This is not to say for a second that we do not possess a biologically given body - as organsims do - whether it is the simplist amoeba to a hook worm dwelling in the guts of an overfed cow; all theoretical positions that posit neurological processes as the determinate of human behavior are variants of good old fashion materialism (look up any standard dictionary of philosophy under materialism). Its nothing new. The early Greek atomists had the notion of the indivisible Atom in the void, subsequenty you had Descarte with a material body (res extensa) and an immeterial soul (res cogitans) as two distinct substances. This position was modified by La Mettrie as "The Man Machine" (which influenced the album by Kraftwork - if I am not mistaken). Here, the soul (psyche - consciousness - ego, i.e. the actual person) is removed from theoretical thinking and replaced by a biologically determined machine. The idea of the human as machine is interesting to think about as depending on the historical worlds homo sapians is inhabiting, the imagination constucts its own self-identificatory mode of expression depending on its surrounding world. Hence as technology developed form wooden horses of Troy to simple machines - human beings came to view their own self image as machine ("mechanism"). Examples in poular culture include Metropolis - replicating ones self as machine, rather than biologically (sperm and egg - and the sexual bodily desires of post-pubescent humans). Or The Terminator films.

Modern scientific management, which has come to influence major segments of capatalist life worlds is also based on mechanism (Images of Organization - Morgan), the lsi goes on and on....

Without going into more detail right now, the point is that there is large amounts of theoretical positions that are based on empirical observation that offere explanations of depression that are not based on the gene that explains everything.

I myself think that there is modulations in the homestasis of neurotransmitters in the CNS under psychoactive drugs. And ther eis also altered states of consciousness. As the body can influence the ego in states of, e.g. fatigue, tiredness, sickness (e.g. virul infection), sexual arousal - so too can the ego influence the body by controlling, inhibiting or giving full release to certain states. There seems to me to be a large variety in phenomenological states of consciousness both 'on' ecstasy and during the comedown and return to baseline. If its as simple as an imbalance of chemicle why the huge varieties of experience. e.g. we took the smae pills but he had no comedown, I dont get depressed but my friends do. Im happy and silly the next day, I get very dark and angry.

I would like to see refences for both sides of the argument. I can certainly provide a detailed list for anyone interested in psychoanalytic or existential/phenomenological accounts of deppession Tellanbach can provide one inroad into to this way of thinking see: Anthropological Psychiatry and Melancholia: a Critical Appraisal. Author: Lolas-Stepke, F. Source: Journal of Phenomenological Psychology, Volume 10, Number 2, 1979 , pp. 139-149(11) Publisher: BRILL.

Recent works on a synthesis on neuropsycholog and phenomenology include the Embodied Mind (Varela); Brain, Symbol and Experience: Towarrds a neurophenomenology laughlin, McManus D'Aquili.

More soon
DX

 

[PsychedelicPeptide]

If its as simple as an imbalance of chemicle why the huge varieties of experience. e.g. we took the smae pills but he had no comedown, I dont get depressed but my friends do. Im happy and silly the next day, I get very dark and angry.

I think some of it has to do with your personality and past life experiences. If you have been through certain types of experiences, you may be better able to cope with the stress of a strong MDMA comedown. Also your life setting would be important. Taking X when you are stressed about other things could cause aversive reactions.

 

[Doc X]

Sure thing

Yeah man, this is the living ego in totality - your past - present - orientation towards the future. And the situation you are in. Such as sitting at a computer thinking about what to say to this message. I don't think we are anywherte near understanding the human brain/CNS in its entire complexity - if such a thing is even possible.

I starting thinking about the marked changes in the different stages of the ecstatic experience and how these might be interlinked. In the peak many people report a bliss, unification, oneness, elimination of wordly concerns, living in the moment "nowness", intense beuty, elation, etc. followed by the lights coming on in a club or rave - and the gradual comedown - scattering as its usually called in Sydney - I think the change in psychic states shifting between the fluctuations in these radically different egoic states may be influencing depressive states. The chemistry of the body is most certainly playing a influence too - but I find that as an all encompassing theory far too simplistic to account for the variety of experiences occuring in these states.

DX

I think some of it has to do with your personality and past life experiences. If you have been through certain types of experiences, you may be better able to cope with the stress of a strong MDMA comedown. Also your life setting would be important. Taking X when you are stressed about other things could cause aversive reactions.