Mental Health The Myth of The Chemical Cure: A Critique of Psychiatric Drug Treatment.

[Sturnam]

You're missing the point of this thread and you've been missing the point of the thread since the first post. I do not contend that AD's do not work. I never have done.

This thread is not debating whether or not AD's work... it's debating whether or not the monoamine hypothesis works...

And for what it counts, I've already cited that I responded very well to Agomelatine, an 'anti-depressant' if you want to call it that. Please stop de-railing the thread with these constant remarks.

You seem to be mixing up the biochemical hypothesis of depression (general! not just monoamine based), the monoamine hypothesis, and the role of antidepressant in it all. Just because the serotonin theory of depression have proven to be less than true doesn't mean that ALL neurobiological theories of depression are false. Because you started this thread with...

'There is not one shred of credible evidence that any respectable scientist would consider valid, demonstrating anything that Psychiatrist's call 'mental illness' are bio-chemical imbalances of the brain.'

And that is just patently false. Here is a short list:
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.
A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder
Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (S) levels in medicated patients with major depressive disorder compared with controls.
Gender differences in serum testosterone and cortisol in patients with major depressive disorder compared with controls.
HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients.
Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression.
Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder.
S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: Efficacy and effects of histamine and carnitine as moderators of response.
Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study.
A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with major depressive disorder.

And on and on and on. I could go on, but I'm sure you get my point, and I doubt that you'll read most/any of these articles anyways. Again, there can be other biochemical imbalances/alterations besides serotonin/monoamines that will contribute towards depression. And sure, maybe this is a round-about way of evaluating biological abnormalities, but you can't exactly take brain tissue from humans. It's pretty unethical. However, if you're willing to look at animal data from depression models, I would be more than happy to find those for you, and I'll even sent you the full texts for free. The animal models have direct brain tissue samples, from different time points, different treatments, etc. But because I expect that you'd want human data, treatment is generally the best data we have as a proxy for underlying pathology.

Now, I would agree with you if you would contest the validity of the idea that improvement of depression with treatment of a drug implies that the drug's mechanism is the source of the problem; i.e. if SSRI's work for depression, then serotonin must be involved in depression. With SSRI's, it's more likely that downstream effects that take longer to kick into gear (3-5 weeks, along the timeline for actual response with SSRI's) are responsible for the antidepressant effects. And here are some sources for that:
Neurobiological mechanisms involved in antidepressant therapies. (serotonin autoreceptors)
Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (neurogenesis)
Interaction between BDNF and Serotonin: Role in Mood Disorders (role of brain-derived neurotrophic factor/BDNF)

And more sources that directly address post-mortem/non-invasive imaging brain abnormalities in humans. I should add that I see structure and function as intimately related, especially for neural processing or alterations, and that biochemical changes can most definitely alter the structure of various brain regions.
Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression
Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies.
Hippocampal atrophy in recurrent major depression
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
Brain Activity in Adolescent Major Depressive Disorder Before and After Fluoxetine Treatment
First-Episode Medication-Naive Major Depressive Disorder Is Associated with Altered Resting Brain Function in the Affective Network
Reduced brain leptin in patients with major depressive disorder and in suicide victims
Brain Biopsy Findings Link Major Depressive Disorder to Neuroinflammation, Oxidative Stress, and Neurovascular Dysfunction: A Case Report


However, I do agree with the general sentiment stated by herbavore, yourself, and others, which is that depression is a complex, heterogeneous disease, and the monoamine hypothesis is stupidly simply, and does not fit with lots of observed data (as you correctly pointed out). It is likely that the downstream effects of SSRIs/SNRIs/etc are responsible for the antidepressant action, and not acute changes in serotonin/norepinephrine/dopamine.

But this does not mean that there are no biochemical changes in depression. Indeed, I believe that who we are, our mood, anxiety, personality, and everything else about us is determined by our biology. Opioids make people euphoric, cocaine can make you an arrogant ass, and LSD can change your thought patterns in incredibly unique ways. And all this happens through manipulation of our brain's biochemistry.

Depression is most definitely understudied, and I would say that we still have absolutely no idea what causes it, what the variations in depression are (situational vs. life-long vs. Seasonal affective disorder vs. major depressive episodes, vs. dysthymia, etc), or how to adequately treat it. Right now we do the best with what we have, which is unfortunately a very narrow band of therapeutics, with most based off monoamine alterations. However, ketamine is doing remarkably well in clinical trials, and is particularly wonderful at inducing a very rapid antidepressant response, and it is not an SSRI. Again, this seems to lend credence to the theory that some alteration in the brain can be rapidly reversed by ketamine, producing an antidepressant response. For the example of ketamine, they think that it is probably related to increased dendritic spine growth (essentially more connection between neurons).(Serial infusions of low-dose ketamine for major depression)

Lastly, medication should always be used in conjunction with therapy, talking to a psychiatrist, therapist, or other. And this is the key bit of information that is often left out, and that people skip out on. Sure, it's much easier to pop a pill every day than to get down to your insecurities/worries/fear/ingrained behavior that contributes to depression, but medication is also much less effective in the absence of therapy. And I think this gets down to the crux of the issue, which is whether the patients need antidepressant medication, or simply some help and guidance through a rough patch in their life.

There are some people that literally cannot get out of bed, cannot keep appointments, and cannot function without antidepressants. However, I see the utility of antidepressants as that little extra push to help people make positive changes in their lives; changes that would be difficult/impossible without the help of medication. Their use is to help people overcome that initial barrier, so that they can go exercise, eat healthy, go to therapy, and other activities that will help ameliorate their depression. And I don't think that most people with depression are in this situation; I think that the vast majority of depression is based on situation; they parents/child/spouse dies, trouble finding work, being alone, no friends, or what have you, and would benefit more from therapy.

I don't really expect you to read most of the references, I just wanted to show you that there is substantial evidence for neurobiological underpinnings in depression for at least a subset of patients, with the most robust evidence of neurobiological abnormalities for severe MDD/lifelong depressive patients, IMO. That is not to say that serotonin or monoamines are the only cause, but they may be involved for some patients. If nothing else, I would really encourage you to read a review on the neurobiology of depression. I think that you might find that the new reviews focus less on increasing serotonin, and look more at neurogenesis, improved synaptic connections, and other theories of depression.

 

[pasha]

^ great post.

 

[herbavore]

Thanks to everyone in this thread that is contributing to the discussion as opposed to contributing to put-downs of those that disagree with them . The discussion is one that I am passionately interested in. The polarized arguments hold no interest for me and so I thank the OP and everyone else who shares my love of investigative, open-minded learning. It is so important to look for the middle ground in language, language that opens panoramas rather than throwing up stone walls. Nothing is more welcome in my world than someone changing my mind through information; conversely nothing is less welcome than someone personalizing what should be an intellectual flow between interested parties.

We edited out a lot of inflammatory posts and hopefully we can keep this very important thread alive and on topic. We live in exciting times as far as brain research goes but I'm sure that we can all agree that what is known now is very little; it's just more than we knew before. I try to read all i can and because of that I know that even what is "known" right now is often in a state of contention. True science asks questions and is comfortable in an uncertain state of exploration.

There are so many articles and books to read posted on here that I plan to check out. Thanks to everyone that linked them.

 

[bees_knees]

Are we all aware there is evidence to suggest that antidepressants boost neuronal regeneration in particular areas of the brain? I don't think it's all areas, but in some that have a lot to do with mood. If you have a faster regenerating brain in your head, you're bound to feel a bit better, and it explains why it takes a while to work. The brain is degenerated in the first place by stress.

 

[AlphaMethylPhenyl]

Generally it's not a good idea to base your points on one source but if the book is in any way shape or form reputable it will list sources too. Those could conceivably be used. Why not list the sources in your book, OP?

 

[Shrooms00087]

^ That's what I did for Chomsky in the Events thread. Pretty good advice

 

[Jerry Atrick]

I don't think you've bothered to read my posts or this thread properly?

If you had done, you'd realise that the title of the book is the basis of discussion, not the source. You'd have known this if you'd read the thread.

I've cited several sources that do not support the monoamine hypothesis. The book being just one of them... Again, you'd have know this if you'd read the thread.

By the way, I've not questioned the efficacy 'anti-depressants'. Again you'd have know this if you'd read the thread.

I've stated that there is some evidence that 'anti-depressants' are no more effective than placebo's in double-blinds, and that there is some evidence that 'anti-depressants' are slightly more effective than placebo's in double blinds. Again, you'd have know this if you'd read the thread.

I've never stated that 'anti-depressants' don't work. I've stated that there is no credible or substial evidence to support the monoamine hypothesis. Again, you'd have know this if you'd read the thread.

Thus, I am lead to believe that any efficacy that they do have, must be owed to another mechanism. Again, you'd have know this if you'd read the thread.

Please read the thread in full before commenting in the future... If anything it just makes you look slightly stupid.

Yep, you caught me. I did not read all your posts word for word. I can skim with the best. The main reason I skimmed is because YOU are too arrogant and wordy. This one post ^ was able to summarize what other 8 or so pages of text you wrote previously in this thread. Now I don't have to read it all. Thanks.

Have you read, The Emperor's New Drugs by Irving Kirsch? This book essentially makes the same argument but it was published in 2009.

 

[cassius14]

Though this thread isn't really directed at anxiety, more Clinical Depression or Major Depressive Disorder... I too believe that TCAs SSRIs, and SNDRIs such as Venlafaxine (Effexor) can be quite effective in relieving some forms of anxiety. Having tried all three classes of drugs for Generalised Anxiety Disorder I'd say that Venlafaxine (Effexor) was the most effective. Though considered the complete emotional blunting, sedation and fatigue that it left me with, I'm not surprised it worked well.

I don't believe the anxiolytic effects of Venlafaxine (Effexor) are so much as an intended cure... but rather a side effect of a taking a rather powerful drug.

eh youre playing with words a little here. side effect by definition is negative and unintended. some anxiety is brought on by depression and vica versa. all depending on the individual. like a lot of medications maybe it was discovered unintentionally but plenty of clinicials I saw i didnt have much depression, more so anxiety and had big thumbs up to venlafaxine, thats hard to class as side effect.

you guys need to remember any drug or AD can never make you do something you wouldn't normally do (include, snap out of depression); not even crystal meth could. AD helps settle people down a bit so they can be in a better frame of mind to make lifestyle changes.

now I tutor statistics at a university level and I study medicine so I can make a half assed call here. simply comparing an SSRI/SNRI to a placebo directly is not terribly smart. first of all, at what margin does a placebo and SSRI/SNRI need to be far away from each other to be considered effective? and even if you come up with a number, that sample you took of people you cannot say all have exact same degrees of depression and their own mental strength/will power to bounce back. how do we know placebo isnt simply those who snapped out of it easier but needed something to believe in, and those where it worked where much deeper in depression/less will power?

you can't infer a sample and two types of reactions to a drug so simply. the human mind is the most complicated device in the known universe. we have figured out how to transport light, we can create antimatter for fucks sake, but we literally have no idea how a lot of the brain works. for instance, the chemical reactions going on to recall a memory? memories totally unique to each person and experience. given that. you cant class and conclude with depression so callously either.

the fact MDMA works so effectively at cheering people up, and someone else here mentioned damaged SRT receptors really screwing people up totally flies in the face of chemical inbalance myth in my opinion. AD are intended to gradually shift neurotransmitters more favourabley for the person. key word gradually.

 

[pasha]

^ great post again.

 

[Flickering]

That is not a "chemical imbalance". That is deep sadness and confusion that has already morphed into hopelessness.

Fucking EXACTLY! It's just that the term we have for that these days IS chemical imbalance.

You could call it that, technically, as any experience is generated by brain activity. But it's not an efficient way for a human to understand it. It staggers me how little we consider the emotional situation of a person's life as it impacts on their mood.

I was very reluctant to go on SNRIs. When I eventually did, I found they leveled my mood so that I wasn't dipping deep into hell at seemingly random intervals. This could easily have been a placebo. I was also almost too tired to move most days, and had to drink four cups of coffee just to get through the day. The doctor said we just had to keep experimenting until we found 'the right one'. Thanks, my brain isn't a fucking dart board!

 

[Rybee]

Sorry, not had a chance to keep up with this thread. Just started a new job and life's been a bit crazy lately.

Does anyone else think that in 50+ years we'll understand depression much better, and like we did with Thorazine, look back and think 'What on Earth were we thinking when prescribing SSRIs?'

Obviously Thorazine had much more devastating effects, but will we look back and think 'Wow, we were way off the mark with SSRIs in the treatment of depression, how could we have been so wrong?' ... or are SSRIs actually a viable solution?

 

[AlphaMethylPhenyl]

SSRIs are pretty useful for the majority of sufferers. Drug addicts have a hard time tolerating substances which produce little to no euphoria--i.e. the opinions of those on bluelight won't lead to an objective conjecture.

 

[herbavore]

Does anyone else think that in 50+ years we'll understand depression much better, and like we did with Thorazine, look back and think 'What on Earth were we thinking when prescribing SSRIs?'

Obviously Thorazine had much more devastating effects, but will we look back and think 'Wow, we were way off the mark with SSRIs in the treatment of depression, how could we have been so wrong?' ... or are SSRIs actually a viable solution?

The adults that took them will form their own valid opinions about them but what upsets me beyond comprehension is the number of children being put on these drugs. Outside of America I don't think this happens very much if at all but here it is already normalized.

 

[bees_knees]

Does anyone have any articles / journals on the atrophy of the brain associated with atypical antipsychotics?

 

[weekend addiction]

SSRIs are pretty useful for the majority of sufferers. Drug addicts have a hard time tolerating substances which produce little to no euphoria--i.e. the opinions of those on bluelight won't lead to an objective conjecture.

I think the real issue is that drug-addicts need something a little stronger than SSRI's. No matter the drug I always had a high natural tolerance. I don't know the science behind it. So maybe SSRIs are just too weak for us?