Why Antidepressants Don't Live Up to the Hype | Hacker News Reader

Why Antidepressants Don't Live Up to the Hype

time.com

23 pointschaostheory26 comments

Actually, it is because research on antidepressants which unambiguously make you feel better - namely, dopamine reuptake inhibitors - was outlawed.

What we're left with are the ones that only work in a mild, sometimes-sort of way. And don't buy the notion that the purpose of an antidepressant is to "correct chemical imbalances." No such imbalances have ever been identified:

http://www.etfrc.com/ChemicalImbalances.htm

"How are the chemical imbalances which are the supposed basis for the prescription of "antidepressants" diagnosed? Is exploratory neurosurgery performed, using some technique that allows the surgeon to quantify synaptic transmitter levels? No, the very idea is absurd. Is a spinal tap, then, done to at least measure, on a gross scale, the distribution of neurotransmitter metabolites? Of course not – how many people have undergone spinal taps before receiving a prescription for Effexor®? Is blood at least drawn, to test something? No. This diagnosis – the diagnosis of the most subtle of chemical disorders in the most complex organ in the body – is made on the basis of the patient's report of feeling sad and lethargic. Try to imagine a hematologist diagnosing leukemia this way to get a sense of just how ridiculous this idea is."

"The principal reason for rejecting biopsychiatry (aside from the fact that intellectual honesty demands its rejection) is that it locates the cause of psychic suffering in people's "bad brains," and excludes the conditions of modern life, or anything else, from consideration as the cause of such pain."

The purpose of an antidepressant is to improve mood. No more, no less. And the degree of doublespeak doctors find necessary to dance around our society's puritanical views on pleasure just to be permitted to market the current, wimpy antidepressants - is staggering.

"No such imbalances have ever been identified"

This guy would disagree:

http://george-eby-research.com/html/depression-anxiety.html

A shortage of certain vitamins (B6, for instance, a precursor to serotonin) will often cause depression. There is, however, no evidence that most depression responds to vitamin supplementation. I fully expect that the reason for this is dead-simple: the modern 9-to-5 treadmill way of life is often the cause, rather than any "disease" in the traditional sense of the word. Your brain is responding correctly to external stimuli.

And there is no shortage of crackpot sites claiming miracle depression cures, just like for any other disease where the medical establishment has proven itself utterly worthless.

"The modern 9-to-5 treadmill way of life is often the cause, rather than any "disease" in the traditional sense of the word. Your brain is responding correctly to external stimuli."

Definitely true. Has anyone written a book about this yet? I know there are books that tangentially touch on it, like bowling alone, but I wonder if there is enough research to do the subject justice.

Well, not exactly book-length, but:

"The Worst Mistake In The History Of The Human Race" (Jared Diamond)

http://www.environnement.ens.fr/perso/claessen/agriculture/m...

The problem cannot be solved by returning to the past: going back to a hunter-gatherer lifestyle would doom 95+% of everyone currently living to starvation. But before a problem can be solved, people have to admit that it exists.

What I'm really interested is data on the specific elements of our lifestyles causing these problems.

Start by reading about the mental effects of sleep deprivation - a problem mostly unknown to pre-agricultural humans. This topic is a hotbed of research, yet the one cure which is certain to work - creating opportunities for people to live lives ungoverned by clocks if they so choose - is of course not on the table.

I realize that a lot of people on Hacker News might consider this to be pseudoscience territory, but what about something like The Biology of Love by Arthur Janov?

http://www.amazon.com/Biology-Love-Arthur-Janov/dp/157392829...

His theory is that the primary cause of mental illness is intrauterine trauma, which negatively affects the structure of the emotional brain at a very crucial developmental stage. This trauma is undiagnosed and untreated in the newborn infant, and persists into adulthood, where it results in depression, addiction, panic attacks, etc.

-----------------------------------------

EDIT: asciilifeform, do you have some kind of axe to grind?

Anyways, here's a few links to scientific studies that support the relationship between intrauterine trauma and mental illness:

Relationship of maternal and perinatal conditions to eventual adolescent suicide

http://www.ncbi.nlm.nih.gov/pubmed/2857957

Obstetric care and proneness of offspring to suicide as adults: case-control study

http://www.ncbi.nlm.nih.gov/pubmed/9812930

Controversial, yes. Without any scientific support, no.

If we're going to go there, personally I prefer the possession-by-demons theory. It is equally plausible and substantiated.

Edit: I don't deny the possibility that prenatal trauma could screw you up in any given way. Attributing all mental illness to it is ludicrous. It is the same situation as with vitamin deficiency - the arrow of causation points in only one direction. There are many ways to break something complicated.

"Lights Out" is a badly-written, breathless, and confusing book on the conflict between our evolutionary capabilities and post/industrial environment, from living conditions to diet. It's absolutely awful...but well-sourced, and broad in scope. I hate recommending it but if you can make it through the cringeworthy tabloid prose the second half of the book contains a decent academic bibliography.

Edit: two writers, one academic and one popular. bad combo.

AFTER EDIT:

research on antidepressants which unambiguously make you feel better - namely, dopamine reuptake inhibitors - was outlawed

Do you have a citation for a law or policy statement that shows that there is indeed such an outlawing? I see Google Scholar citations that suggest that research is ongoing, and there is more planned.

http://www.ajp.psychiatryonline.org/cgi/content/abstract/163...

/AFTER EDIT

There are more than 100 countries in the world, and they would have to be united in banning a certain direction of research for there to be no research on that subject. But dopamine reuptake inhibitors, based on ongoing research in various places, are a risky approach to treating major mood disorders.

"DRIs are notorious for their high abuse potential and ability to cause addiction and dependence. Pure DRIs such as cocaine and combination releasers such as amphetamine and methamphetamine are widely abused throughout the world."

http://en.wikipedia.org/wiki/Dopamine_reuptake_inhibitor

"NDRIs approved to treat depression

"Here is the only NDRI that has been approved by the Food and Drug Administration specifically to treat depression, with its generic, or chemical, name followed by available brand names in parentheses:

    * Bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL)"

. . . .

"Safety concerns with NDRIs

"Bupropion can increase blood pressure in some people, so regular monitoring is important. The risk of developing high blood pressure may increase if you also use nicotine replacement therapy, such as a nicotine patch, to help you stop smoking.

"There's a small chance that taking bupropion can cause a seizure if you've had previous seizures, a head injury or a nervous system tumor, or if you've had an eating disorder, such as bulimia or anorexia. Because of that, don't take this medication if you have a history of seizures or eating disorders or if you're abruptly discontinuing use of alcohol or sedatives. Be sure to tell your doctor about your past medical issues.

"Also, because of potentially dangerous medication interactions, be sure your doctor knows about any current or previous use of monoamine oxidase inhibitors (MAOIs). Tell your doctor also if you have severe liver cirrhosis, because Wellbutrin can cause liver problems. In addition, don't take Zyban while you're being treated with any form of Wellbutrin."

http://www.mayoclinic.com/health/antidepressants/MH00068

Notice how Wellbutrin - the 1970s state of the art - is what we're stuck with. Precisely because research has been curtailed - yes, internationally. Progress stands still.

Also compare the side effects you listed with those of the wildly popular SSRIs.

And yes, any hypothetical drug which reliably makes you feel better will be addictive in some sense of the word. Deal with it, and move on with life. Addiction is only the bugaboo it is claimed to be when the thing you are addicted to is actually harmful. Most people don't consider themselves "drug addicts" for using caffeine, for example.

The focus should be on developing drugs which do the mood-lifting job, don't produce tolerance, and don't damage your internal organs. There is no evil spirit which manipulates the universe to make this goal impossible. It is simply considered undesirable by our Puritan rulers (and the outposts they have built inside our own heads.)

Reply to Edit:

> Do you have a citation for a law or policy statement that shows that there is indeed such an outlawing? I see Google Scholar citations that suggest that research is ongoing, and there is more planned.

Check out the Federal Analogues Act (US) and its foreign equivalents. Any drug which is chemically similar (with a very liberal definition of "chemically similar" that provokes howls of laughter from chemists) to a currently banned drug is instantly placed into "Schedule I" - "no medicinal use" - and is outlawed, in such a way as to make research nearly impossible and certainly unprofitable. But the real problem lies with our society's perception that a drug which gives you pleasure is an unambiguous and unmitigated evil all in itself, regardless of whether it has harmful side effects. Few of the research drugs in the papers you've seen will be permitted on the market, for this reason. Certainly none of the ones which actually work will be.

By deliberately marketing antidepressants which only work subtly and sometimes, the pharmaceutical industry continues to uphold the ruse that they are actually treating an ordinary disease, like leukemia. But we know how to build antidepressants which work on everyone. It isn't being done because if it were, the smoke would clear, and we would be forced to admit that we are actually treating unhappiness. Unhappiness caused by stimuli which ought to make a sane person unhappy.

But we know how to build antidepressants which work on everyone.

It took me a while in my offline personal life for the very evident counterexample to come to mind. In fact, it is well known that human mood can go wrong in two ways: by being too low (depression) but also by being too high (mania). To date, there isn't any medication that reliably raises the mood of individuals in normal mood states without subjecting some of those individuals to severe risk of psychotic mania. Anyone proposing policy reform as to this issue should be aware of this fact. Here are some reading references for HN participants who would like to know more about the medical research on mood disorders:

Depression: Causes and Treatment, 2nd Edition

http://www.amazon.com/Depression-Treatment-Aaron-T-Beck/dp/0...

(a very recent book, by the inventor of cognitive therapy)

http://www.amazon.com/Manic-Depressive-Illness-Disorders-Rec...

(a very authoritative textbook with extensive references to primary research literature).

That's all true. But nobody says 'oh, you're addicted to blood pressure regulators or (other medication for chronic conditions)'. Informally, my experience is unhealthy levels of dependence seem to manifest in people who don't have a deficiency in the first place. Unless one's neurological deficiency is really severe, one often develops a methodology to live with it. Absent that know-how, it's a lot easier to overdo it and end up in the ditch.

"The purpose of an antidepressant is to improve mood."

I'd say that their effect is that they reduce the amplitude of emotions, so to speak. You get sad, but not -as- sad; however you also don't get as happy as you might have been otherwise.

This is a reason that some people don't like taking such drugs: they feel it takes away their emotions and transform their personalities.

> they reduce the amplitude of emotions

SSRIs appear to have this effect in many people, but it is not universal to all antidepressants. See my other comments in this thread.

Not to get into an argument not medically qualified, but as some who has extensive experience with both recreational and clinical drug use, asciilifeform makes some good points here.

Yes, it's absurd that psychiatry often doesn't involve any blood tests, which really makes to hard to take seriously as a medical discipline. I've had both good and bad psychiatrists, but it's hard to escape the conclusion that 'fill this prescription, tell me how it's working in a month' is not much more than licensed drug dealing. SSRIs and suchlike are designed to build up their effect over time rather than supplying instant chemical gratification, which is a good idea, but as medical tools I think they're fairly half-assed.

Between study, experience, and practice at observing my reactions, I feel moderately competent to monitor my own brain chemistry, at least as well as any lay person can. Mapping out the metabolic curve of a drug in the body isn't so terribly hard and SSRIs feel very much like the chemical equivalent of treating the symptom rather than the cause. In short, they seem to flatten affect, such that the amplitude of yuor mood swings is reduced and you don't care how you're feeling to the same degree as normal. On several occasions I've taken a course, been quit disappointed, and come off them - subsequent improvement, if any, has more to do with increased self-regard for having taken action to address the problem.

I do feel, strongly, that dopamine deficiency is part of my particular problem - and as pointed out, the clinical options there are somewhat limited. It's on reason I still smkoe; nicotine is a very effective dopamine agonist. Unfortunately, it's brought me to first-stage emphysema and every time I light up my lungs ask me why there isn't a better way. Although I have been diagnosed with moderately several Adult ADHD (via interviews and tests...another example of the medical catching-up psychiatry needs), my doctor's been rather reluctant to break out the Adderall or suchlike because he worries there might be a potential for abuse. At his hourly rate, I don't argue, but frankly I'm OK with it because it can hardly be worse than tarring my lungs. My past experience with illegal stimulants like cocaine is that they're quite enjoyable but don't exercise any significant compulsion on me. I took the latter semi-regularly for a while but got bored with staying in and having the same wired conversation with my roommate, so I just dropped it.

Just my anecdotal perspective. I find it depressingly easy to understand why so many people wind up 'on drugs'. They work, but it's infra dig to start your clinical approach from there.

This is an important article following up on the many studies of serotonin-specific reuptake inhibitors (SSRIs) from the 1990s. It turns out, as usual, that the drug companies were quick to publish studies favorable to their products, and slower to publish studies unfavorable to their products. See the excellent article by Peter Norvig, director of research at Google, on how to interpret scientific research,

http://norvig.com/experiment-design.html

for more on this problem of publication bias.

There is a good body of research now suggesting that most patients with depressed mood and related symptoms can be helped by cognitive therapy.

http://www.aafp.org/afp/20060101/83.html

http://www.apa.org/divisions/div12/rev_est/cog_depr.html

For many persons suffering from depression to the degree that it interferes with work or with family relationships, the best approach will be to combine medical treatment, possibly with the new first-line drugs (SSRIs) or possibly with other drugs, and cognitive therapy to learn new patterns of thinking.

Summary: company funded studies claim drugs help X% of the population. More rigorous federal studies show they might only help 2/3 * X%. The main difference in the groups was including drug abusers in the federal group.

So what? A drug either helps you or it doesn't. If it helps you, you don't care what fraction of other people it helps.

The value of X mainly determines how many drugs you'll need to try. If they work for 50%, you'll have to try 2 drugs on average before finding one that works. So you want to start with drugs with large values of X, but whether it's 60% or 40% isn't a huge deal.

Furthermore, clever doctors can often guess right and prescribe different drugs for different people. Studies that insist on giving the same drug to everyone with depression are stupid, because they're administered much more intelligently in the real world.

What's interesting is that antidepressants such as Prozac have a few established, proven and well-documented side-effects, one of which is orgasm inhibition:

http://en.wikipedia.org/wiki/Ssri#Sexual_side_effects

So I'd imagine that the men who are prescribed antidepressants for things like premature ejaculation find that they very much do live up to (a different kind of) hype.

From personal experience, I can say that the compulsion (to have sex) remains but the pleasure doesn't, resulting in a lot of frustration. I prefer the mood swings. I'm pretty skeptical of this as a therapeutic option for p.e..

I've taken an interest in body chemistry and especially neurotransmitters over the past year or so. One thing that I've noticed is that every drug I've come across that acts as a neurotransmitter reuptake inhibitor has bizarre and highly undesirable side effects not directly related (as far as anybody knows) to increasing the levels of the neurotransmitter in question. I think very few people should take drugs in this class, and they should be used as a last resort, not the primary treatment for any condition.

If it is desirable to raise the level of a given neurotransmitter, I think supplementation with precursors is a more favorable approach. For treating depression, it is likely that raising serotonin and dopamine levels simultaneously will have the desired effect. The appropriate precursors are 5-HTP and levodopa. To aid in production, it may be helpful to take vitamin B-6. To help cause production in the brain instead of the rest of the body, it is advisable to take an aromatic L-amino acid decarboxylase inhibitor that does not cross the blood-brain barrier. EGCG (green tea extract) is effective for this purpose, and may restore proper brain chemistry on its own.

This is not medical advice, and while all the chemicals I've mentioned are available as dietary supplements, they have significant biological effects, including the possibility of harmful side effects. Do your research, and don't rely on advice from the health food store by itself. Wikipedia is a good starting point (though, obviously, it shouldn't be the only source you consult).

A good outline of the process:

http://yarchive.net/med/5-htp.html

This is the first time I've seen the claim that B6 will significantly increase serotonin production outside the brain when taken in combination with 5-HTP and an AAAD inhibitor. It certainly does without the AAAD inhibitor, and it seems possible that it would even with.

This backs up my previous point though - do your research if you're considering self-medication.

Whatever the effect, the withdrawal symptoms associated with addiction to big brands like Effexor make beginning to take them something one should seriously consider. I was on Effexor for 2 years and, while it did have a slight positive net effect on me, in the end weaning myself off of it was difficult and very uncomfortable. The addiction is so strong that even a doctor supervised, long term (2 months) withdrawal regimen was a bad experience.

I think this blog post (linked from the original article) is more interesting than the article itself:

Antidepressants, Placebos and the Failure of Psychiatry

http://neuroskeptic.blogspot.com/2009/03/antidepressants-pla...

Reply on news.ycombinator.com