Posted by: Mark | 2005/11/21

On antidepressants? Depressed? Read this...

Here is some confusing news for those suffering from depression, whether you are already using antidepressants or not.

Jeffrey Lacasse and Jonathan Leo (a professor of anatomy and his doctoral student) recently published the article "Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature" which is a review of all peer-reviewed papers on the link between serotonin levels and depression. You can easily find this by searching for their names and the name of the article.

Their conclusion? "Not a single peer-reviewed article ... support[s] claims of serotonin deficiency in any mental disorder."
What is "peer review"? When researchers wish to publish their findings they submit their papers for publication to one of a number of reputable industry journals. The editors then get other experts in the same field of expertise to review the paper before it gets published.

What is going on here? Don't we all know - thanks to television and print advertisements, magazine and newspaper articles, and advice from our doctors - that depression is caused by a deficiency of serotonin, a brain neurotransmitter chemical? And that taking SSRI antidepressants (Zoloft, Paxil, Prozac, etc) will correct this imbalance?

Well it turns out that none of this is supported by any scientific studies!

But people could be forgiven for thinking that (a) depression is caused by low serotonin levels and that (b) ssri's will alleviate depression because, as the authors also found, "Regarding SSRIs, there is a growing body of medical literature casting doubt on the serotonin hypothesis, and this body is not reflected in the consumer advertisements".

What can you do? If you are suffering from depression - seek help from a real person, not a pill in a bottle! Consult a psychologist/alternative therapist - don't worry, it's also covered by your medical aid. Take back your life! Take back your power!
My wife was on antidepressants and I can tell you that she was a shadow of her former self, like a zombie. Ask people dear/near to you for their honest opinion about how you've changed since starting the drugs.

This is especially shocking news for those who have been brow-beaten by doctors into feeding these drugs to our children (I resisted). Do your research, inform yourself - you are responsible for your child's well-being. And follow the "precautionary principle" - in the light of such uncertainty, do you really want your child to be part of an experiment based on unproven science?
BUT be careful - SSRI's are powerful drugs and should not be discontinued abruptly! Ask your doctor for a safe schedule.

I suggest you print this information because it is likely to be deleted by the forum administrator ... please note that I have nothing against doctors - I believe they are generally very well-meaning and dedicated individuals. Unfortunately, they are treated as "useful fools" by the drug industry, and misled with the same misinformation as used against the public.

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Our expert says:
Expert ImageCyberShrink

No anatomist, let alone anatomy student, let alone at an Osteopathic School, is qualified to comment on matters of neuro-biochemistry.
And what you neglect, Mark, is the blatant doubel standards you are applying. Despite a significant body of scientific research showing benefits from using these drugs, you reject all that because an unqualified person thinks they could be faulty. But you recommend insead "alternative remedies" when in the entire universe, not one single shred of evidence exists that ANY alternative therapy is of the slightest benefit whatsoever. How dare you describe ANYTHING as "based on unproven science" when you airily recommend therapies without any proof whatever ?
IF you are to be credible, you need to apply the same standards to each of the alternatives you are supposedly comparing.
And anhy Medical Aid that covers visits to any alternative therapist / quack, is blatantly and disgracefully wasting their customers money.
"These drugs " should be used only very sparingly and cautiously in children, yet one has to recognize that serious Dpresion can ocur in kids, among whom suicide is not rare, and alternative remedies are perilous.
Nobody should be brow-beaten into taking any treatment ---not merely drug industry mediations --- people ought to be very cautious about ANY therapy offered to them without science and evidence to back it --- such as Scientology, "natural" remedies, and hypnosis. But I can't help feeling, from the tone and content of your postings ( under various names, but I can read the incoming IP address, remember, so just stick to one nickname ) you sound very reminiscent of the "useful fools" used by Scientology to try to discredit psychiatry, their rival for profit-making, in marketing totally unproven and wildly unrealistic theories and treatments. Giving up on providing any evidence that theyr treatments work, they content themselves with attacking orthodox reatments which do have such evidence.
Mike, don't let amateurs like this mislead you. There is an enormous volume of excellent and weighty reseach about the workings of the brain, a topic which is so immense and complex as to be hard to summarize. Because nobody wants to drill holes into people's skulls and extract live brain samples for analysis, research methods have to be subtle and indirect. The relevance of serotonin is a theory, and a reasonable one. If a drug which predominantly boosts the availability of serotonin helps a large proportion of depressed people to become less depressed, it's fairly reasonable to asume that low serotonin levels or availability might be part of the causation or process of Depression.
But Mike, no competent psychiatrist would prescribe Prozac to "mellow" someone or for somone not suffering from a severe and distinct psychiatric condition.
And Michelle, I think you acidentally misquoted a sloppy sentence in the original article ---there isn't a shred of evidence that "psychotherapy" is equivalent to drugs in effectiveness in treating Depression --- all the evidence shows that one specific form, Cognitive-Behaviour Therapy, can be equivalent ; and that most other forms of psychotherapy, espcially the analytically-oriented, are useless or worse.
Peter Breggin is an eccentric who seems obsessed with eradicating the SSRI's, and sems to focus on nothing else. Notice that when Carte Blanche wanted to do a piece knocking these drugs, they flew to interview him, apparently unable to find any other person so reliably negative. His views are NOT widely accepted in the scientific and medical community. I don't recognize the journal "PLos Medicine" --- what is it ?
Now The Wall Street JOurnal is indeed a generally reputable paper --- but you have here a journalist, lacking scientific qualifications, uncritically summarizing this single paper she found in a journal. And we remember so often when major papers, including the New York Times and other highly repurable journals have found reporters who invented stories and the evidence to prove them --- I'm sure she is doing a fair summary of this particular article, but past experiences forbid us from accepting any journalistic article in any paper or journal, as a reliable source.
And the advantage of science is that it encourages, indeed demands, this sort of questioning of current theories, an attempts to disprove them. Notice too, that Mark actively misuses this aticle and the entire debate --- they are not quoting ANY evidence that SSRI's do not work as effective antidepressants -- the argument is entirely about HOW they work,. And that is fruitful. The neurogenesis theory is a very promising one, and it fits with the observation many of us have pointed out for decades --- the lag-time before any antidepressant shows distinmct antidepressant effects has to be significant ( and its also a reason why I am deeply dubious when any new antidepressant is marketed as working much more quickly than the others ).
You can see how naive and devoid of practical experience are the Anatomist and the journalist, when she writes falsely that the advertising of SSRI's is somehow "keeping patients from a therapy that will help them more." You will notice in this forum that I am second to none in promiting the use of CBT. But no drug advert keeps anyone from having CBT, and we encourage their combined use.
What limits it's use is several important factors. Medical Aids, none of wich seems interested in really good medical / psychiatric advice on their policies, reward doctors more for prescribing medications than for sitting talking with patients, as CBT requires. The payment system actively discourages any form of psychotherapy, which requires TIME, something they're very reluctant to pay for. A surgeon might get paid more for a complex op that takes longer, a shrink is not. Within State health services, the administration is so lousy, and the workload so high, that doctors and shrinks cannot aford the time to provide such counselling, in most instances, and are pushed towards the quickest possible solution --- writing a prescription.
Another factor limiting this is the slowness of Medical Schools to provide training in CBT, and reluctance to recognize that, so long as a proper diagnosis has been made by a properly trained shrink, other health professionls can also be trained to provide the therapy well and efectively. There are few opportunities for existing shrinks to learn the technique, and no incentives to do so. The Medical Council requires doctors to undertake continuing education, but in a highly stupidly designed course which allows a handful of people and organizations to make a lot of money by providing sub-standard or unneeded trai9ning, and which does not encourage this sort of much needed training.
Finally, the Council's obsolete and anti-competitive rules limiting anything they conside to be "advertising" by health practitioners, makes it almost impossible for patients to discover who has had relevant training and can provide CBT.
So, where does all this debate get us ? SSRI's DO WORK, this is not the issue being challenged. Exactly how they do so is irrelevant to someone who needs an effective treatment right now. It is very relevant to science in that the better we understand how they work, the better we might devise other treatments which will do exactly what is required, even more efficiently, and perhaps with less side-effects. And CBT does work, nobody with any sense denies that, but there are problems which need to be urgently addressed, to make it much more widely available.

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Our users say:
Posted by: Dee | 2005/11/22

Well - What I know for sure is that for now - until something better comes along - the meds have bought me time here on earth. When you are suicidal - thats all there is and it is a very very fine line between life and death. I am not discounting psychotherapy in the least or even CBT(shich I am down for), but when your back is against the wall - emergency measures are necessary.

I told my psychiatrist that she had to convince me that the drugs were my best option and she had to draw the whole physiological, psychological, biochemical, and endocrinological link for me using STICK FIGURES so that I would understand exactly whats going on.

I have never thought that depression is caused through a lack or low level of serotonin but rather that by increasing the levles of serotonin, it helps to get you out of a depressive state.
I think that when you do get out of that debilitating depressive state - THATs when you find yourself a damn good psychotherapist and or CBT expert.
Before that - very litle might penetrate your mind whilst you feel like you are in a black hole - not even a therapist.
I think it is dangerous to suggest that the meds are not doing the right thing - when for some of us, it is our only lifeline.

Reply to Dee
Posted by: JSS | 2005/11/22

Oh boy. These articles don't make me feel any better. Cybershrink, what say you?

Reply to JSS
Posted by: Michelle | 2005/11/22

Ok, here's the original article. You will see, Mike, that the link between serotonin and depression is tenuous, at best. What is acknowledged, though, is that the SSRI's do have some effect on neurological function - but that it has very little to do with boosting serotonin levels to lift depression.
The most interesting finding is that psychotherapy is equally effective at treating depression as SSRI drugs. And if you take into account the placebo effect (80% effective according to the original article), then the SSRI's have precious little going for them.
If they only had beneficial effects it might still be worth using them - but the list of nasty side effects clearly makes the risk unacceptable. A quick google search on "Peter Breggin" will reveal plenty. He is the Harvard Med School doctor who has been most critical of SSRI's.

And '...' it is no wonder that you could run a mile on the drugs - one of the amphetamine-like side effects of the drugs is that they can induce a state of "mania".

Here is the article from the Wall Street Journal's Science Journal - a reputable publication. A similar article appeared in New Scientist.

Some Drugs Work To Treat Depression, But It Isn't Clear How
November 18, 2005; Page B1
Hardly any patients know how Lipitor lowers cholesterol, how Lotensin reduces blood pressure, or even how ibuprofen erases headaches. But when it comes to Prozac, Zoloft and Paxil, ads and glowing accounts in the press have turned patients with depression into veritable pharmacologists, able to rattle off how these "selective serotonin reuptake inhibitors" keep more of the brain chemical serotonin hanging around in synapses, correcting the neurochemical imbalance that causes depression.

There is only one problem. "Not a single peer-reviewed article ... support[s] claims of serotonin deficiency in any mental disorder," scientists write in the December issue of the journal PLoS Medicine.

Indeed, a steady drip of studies have challenged the "serotonin did it" hypothesis. A 2003 mouse experiment suggested that SSRIs work by inducing the birth and growth of new brain neurons, not by monkeying with serotonin. In March, a review of decades of research concluded that something other than "changes in chemical balance might underlie depression." And as Jeffrey Lacasse and Jonathan Leo write in PLoS Medicine, although ads for SSRIs say they correct a chemical imbalance, "there is no such thing as a scientifically correct 'balance' of serotonin."

How did so many smart people get it so wrong? Medicinal chemist Derek Lowe, who works in drug development for a pharmaceutical firm, offered an explanation in his "In the Pipeline" blog. "I worked on central nervous system drugs for eight years, and I can confidently state that we know just slightly more than jack" about how antidepressants work.

It is not for lack of trying. In 1965, psychiatrist Joseph Schildkraut of Harvard University suggested that a deficiency of a brain chemical causes depression. With the success of drugs that block the reuptake of these chemicals, that idea started to look pretty good.

Yet the evidence was always circumstantial. You can't measure serotonin in the brains of living human beings. The next best thing, measuring the compounds that serotonin breaks down to in cerebrospinal fluid, suggested that clinically depressed patients had less of it than healthy people did. But it was never clear whether depression caused those low levels, or vice versa. A 2002 review of these early experiments took them to task for such flaws.

There had always been data that don't fit the serotonin-imbalance theory. Depleting people's serotonin levels sometimes changed their mood for the worse and sometimes didn't. Sending serotonin levels through the roof didn't help depression, a study found as early as 1975.

There is little doubt that the SSRIs do what their name says, keeping more serotonin in the brain's synapses. But the fact "that SSRIs act on the serotonin system does not mean that clinical depression results from a shortage of serotonin," says Dr. Leo, professor of anatomy at Lake Erie College of Osteopathic Medicine, Bradenton, Fla. No more so, anyway, than the fact that steroid creams help rashes means that rashes are caused by a steroid shortage.

A clue to how SSRIs do work comes from how long they take to have any effect. They rarely make a dent in depression before three weeks, and sometimes take eight weeks to kick in. But they affect serotonin levels right away. If depression doesn't lift despite that serotonin hit, the drugs must be doing something else; it's the something else that eases depression.

The best evidence so far is that the something else is neurogenesis -- the birth of new neurons. When scientists led by Rene Hen of Columbia University and Ronald Duman of Yale blocked neurogenesis in mice, SSRIs had no effect. When neurogenesis was unimpeded, SSRIs made the mice less anxious and depressed -- for rodents. As best scientists can tell, SSRIs first activate the serotonin system, which is somehow necessary for neurogenesis. That is what takes weeks.

Claiming that depression results from a brain-chemical imbalance, as ads do, is problematic on several fronts. Patients who believe this are more likely to demand a prescription. If you have a disease caused by too little insulin, you take insulin; if you have one caused by too little serotonin, you take serotonin boosters.

Most people treated for depression get pills rather than psychotherapy, and this week a study from Stanford University reported that drugs have been supplanting psychotherapy for depressed adolescents. Clinical guidelines call for using both, and for psychotherapy to be the first-line treatment for most kids.

Psychotherapy "can be as effective as medications" for major depression, concluded a study in April of 240 patients, in the Archives of General Psychiatry. Numerous other studies find the same.

The hegemony of the serotonin hypothesis may be keeping patients from a therapy that will help them more in the long term. The relapse rate for patients on pills is higher than for those getting cognitive-behavior psychotherapy.

Some 19 million people in the U.S. suffer from depression in any given year. For many, SSRIs help little, if at all. To do better, we have to get the science right.

Reply to Michelle
Posted by: mike | 2005/11/21

Ref last posting, I agree you may and others have had good results with medication, but I think with all the unknowns it is best not to count on medication for all individuals problems. I'm glad that you've had good results from your meds, I to am on 20mg of fluoxetine (Prozac) not for depression but to mellow me out a bit. So far for me things seem to be going fine and I've not noticed any negatives or had anyone near notice anything. In fact when I work on something I'm more focussed. But I'd still like all the FACTS and alternatives. I still think it's more hit and miss than the single cure all.

Reply to mike
Posted by: ... | 2005/11/21

I see you are on a mission to tell the world about terrible effects of anti - depressants.... as for asking people whether i am better on or off the meds- i don't need to! I know how I FEEL when I am on meds and i know that people around me are much more at ease too... nowhere near a zombie at al! They are effective and treat the cause of my problem. It's simple actually. I have tried going off meds many many times and i always land up back where i started - suicidal.
I don't care what people tell me about these meds, they have helped me live a better life. I was anti any medication previously, but thanks to meds I can live my life's dream and not be stuck in deep dark hole, feebly trying to listen to people like you who tell me to take back my power, when i don't even have the energy to get out of bed.
Only people who have never experienced those pits of despair, can sit back and tell you to take back your life. What if you never ever had a life before meds???????????
I know your intention is most probably a good one, but when you visit sites that are geared to find the info you are seeking, then you're going to find it.
There are also lots of sites online saying that HIV doesn't cause AIDS - so, if that is what you wish to believe, you will find so called "Theories" to back them up.
Hell, there are people out there who still believe the earth is flat....... and they have all their evidence to prove it. For me, the evidence is in MY experience and I refuse to take that fickle advice of taking control of my life, when just to wake up was more of a struggle for me than it would be for an average person to run a marathon............
Thanks to meds.... I can now run a marathon if I wanted to do so.

Reply to ...
Posted by: mike | 2005/11/21

I'd like to know if the relationship between serotonin and depression is a medically and scientificatly proven fact or just a theory? Remember ice pick lobotomies at one time were one mans theory that was widley adopted and later proven to not only be wrong but harmfull. I've read medical science has little factual understanding of the brain, how then can messing with the chemical make up of someones brain be justified if all the facts are not in? Working in a specialized prison that deals specifically with meantally ill inmates, and some just violent ^&*^&*(^. From what I've seen from our states Psychologists and Phsychiatrists is a hit and miss approach to mental illness. I've yet to see anything impressive and I've been there 12 years. They really have no idea about anything being a fact in regards to a persons mental make up.

Reply to mike

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