Why antidepressants don't work..

Miscellaneous and Personal Stuff I Must Share
21

IANAD, but you may want to do some research on Bipolar Spectrum Disorder and/or read the book Why Am I Still Depressed? by Jim Phelps. In sum, there are people who have been thought to be unipolar depressed but who are actually on the bipolar spectrum, meaning that their main symptom is depression with atypical mania or hypomania that isn’t recognized as such. For people with Bipolar Spectrum Disorder, anti-depressants may give a bump (or cause mania within the first few days of taking them), but eventually they wear off or stop working or don’t work as well. It strikes me that Zoloft made you manic (or what reads as manic to my eye) but that Lithium was helpful. To my untrained eye, this sounds like Bipolar Spectrum Disorder. But, again, IANAD.

If you are still taking lithium, or you found it helpful but the side effects intolerable, you may want to ask your psychiatrist about Lamictal. It is a mood stabilizer that doesn’t cause the side effects of lithium.

22

Perhaps the study should have been hailed as confirming that antidepressants do work, because obviously the people for whom they matter most are the seriously depressed, no?

The media’s claims that antidepressants are no better than placebos really get my goat. If studies of chemotherapy drugs were reviewed and it was found that only patients with the most malignant forms of cancer benefited from them, would the finding be similarly reported? I’m guessing that this at the very least would be seen as unethical because chemo drugs do hold out some hope to cancer patients. Well antidepressants hold out hope to those of us with depression. And with good reason.

23

A placebo broke my dick? Hard to believe.

Knead
Glad he’s getting laid regular and doesn’t need the meds any more

24

This is a lot more complicated than “antidepressants don’t work.” They do work sometimes for some people, although I think some studies show they all work at about the same rate - but they don’t all necessarily work for the same people. But if the drugs are much more likely to work for people with the most severe depression, that indicates people with less severe depression should try other options, and I don’t know how often that happens: we may be too quick to turn to drugs as a solution. The fact that they sometimes work also does not mean that something else might not work better: I’m no doctor, but I have doubts about our understanding of brain chemistry. “Blunt instrument” sounds right.

Cancer is, for lack of a better word, more specialized than depression is. Most cancer drugs only work on certain kinds of cancer and some are used only in patients with the most malignant tumors because of their side effects. So research would probably reveal information like this would ahead of time. But if a study showed that a certain drug worked only on the most malignant tumors, doctors would start prescribing it for those tumors and stop using it on other patients. I don’t think people take that kind of a view on antidepressants: they’re seen as something you can take for mental health maintenance the same way you might take a different drug to keep your cholesterol down. Perhaps that’s not the way they should be prescribed.

25

It’s a gross oversimplification of the study to conclude that “antidepressants are no more effective than a placebo, and may be worse.”

First, it was a meta-analysis, a type of study many find less compelling and potentially subject to flaws, compared to a good multi-center clinical trial (for instance).

Considerable benefit was found for antidepressant drug treatment in people with severe depression.

I don’t doubt that for many with milder forms of depression, a placebo might work as well. I recall a study not long ago that found that St. John’s Wort was no more effective than placebo in treating mild to moderate depression, a paper that got quite a bit of publicity. Interestingly, the standard tricyclic antidepressant they compared SJW to, failed to beat the placebo either.

These are not exactly innocuous drugs, and there’s reason to believe they are overprescribed. They’re also lifesavers for many people, and it’s a damn good thing we have them instead of (as in the old days) having to rely on either shrinks or well-meaning dodos telling us to cheer up.

26

This is perhaps one of the problems with how we view these drugs. As (just as by one poster above pointing out the tricky issues w/ Bipolar depression vs. unipolar depression) there are plenty of different types of depression, and there are different categories of Antidepressants as well, it’s not something where one drug treats all, but rather the problem lays in trying to accurate diagnose the right type of depression first and then match it to the right type of therapy for the person.

Perhaps we do need to work on how we view depression as a whole in regards to antidepressant medications.

27

Desipramine saved my life and sanity, thank you very much.

How’s L. Ron these days?

28

I’m glad that a number of people here were able to gain some relief from depression or similar issues after beginning to take some particular antidepressant. But those of you saying “To hell with this study; if antidepressants are little more effective than placebo, then explain how it was that I had this experience” realize this is exactly the kind of anecdotal evidence this board is dedicated to pooh-poohing when used to prop up myriad other popular scientific and medical claims, right?

Not that I’m saying antidepressants are little more effective than placebo (or even that that is exactly the conclusion claimed by the study). I’m just saying the counter-posts don’t really carry the demonstrative weight they seem to attempt to, whereas scientific studies (though I’m not familiar with this one and can’t vouch for it being well-designed or not) are the only sort of thing which could.

29

No one’s saying antidepressants are mere sugar pills. They clearly have significant effects. It’s just that, possibly, on average, the effects that they have are no more effective at the task of mitigating (certain kinds of) depression than placebos.

30

You know how you can tell if an antidepressant works? If it works. Between me and a couple family members and a couple friends, there’s more than a placebo’s difference between off meds and on meds. For me, the changes are subtle and unconscious, and usually surprising. A placebo would tend to work the way you expect it to.

31

That’s correct, if somewhat tautological. But the mere fact of an antidepressant (or anything else) working for some people, even working where inert placebos have failed, even working in a very noticeable manner, even working by means of effects which it produces which would not be produced by an inert placebo, tells you, in itself, almost nothing about the question as to whether antidepressants are any more efficacious on average than placebos. To answer that question, you have to carry out large, well-designed trials and tally up the results.

32

Since you asked:
there is such an effect, though not quite in the way you described it.

It’s the ever so fun to say Nocebo
Basically it’s the same thing as a placebo, except the patient gets an inert drug that makes them feel the side effects of said “medication”.

So it’d only apply to you in your case if you were given a sugar pill/non-drug and then told of the side effects of the real drug, and then you experienced those same side effects because you were expecting to feel them.

33

This is nowhere near as comprehensive as I would want it, partly because it’s late and I’m tired:
Depression is linked to an imbalance in neurotransmitters (NTs), most commonly they involve the three main ones, serotonin, dopamine, and norepinephrine (NE).
Back in the 1950’s the first, the first generation of antidepressants were introduced, the monoamine oxidase inhibitors (MAOI). The inhibited the breakdown of all three NTs, but were discontinued when it was reveiled that they had bad side-effects. Currently, MAOI’s are only in patients that don’t respond to typical contemporary antidepressants.
The next generation of antidepressants were the tricyclic antidepressants, i.e. Elavil. They blocked the reuptake of NE, and some blocked also serotonin.
The breakthrough, though, was the introduction of selective serotonin reuptake inhibitors (SSRI’s) like Prozac, Paxil, Zoloft, Luvox, Celexa, Lexopro to name a few from the top of my head.
These increased the serotonin levels between synapses by making the serotonin stay in the synapse longer. The typical diverse effects of these antidepressants are attributed to that there are at least 12 types of serotonin receptors in the brain. In which case, despite the challenges, it’s also helpful to have numerous types of receptors in that there are many types of serotonin mediated depression, affecting appetite, anxiety, etc.
The newer ones are NDRI’s (inhibits NE/Dopamine uptake) like Welbutrin. and SNDRI’s (inhibits serotonin and NE uptake) like Eflexor, Cymbalta, and Pristiq.
The problem here lies in that ALL of these antidepressants are equally effective. The success rate is determined by trial and error, to understand what is better for the patient to take. The reason for this is due to co-modulation. For example, with an SSRI, that increase the level of serotonin, but it can cause fluxuations in the levels of dopamine and NE in a unpredictable fashion.
To complicate the problem further, all of these drugs react differently in people, leading to either sensitization or desensitization of the receptors that the NTs are affecting.
However, I believe there’s a new drug on the horizon, the so called “TRI’s.” (or SNDRI’s) These are selective inhibition of all three NT’s. But the problem lies in that the end profile of the brain shows the same profile as addiction.

I conclude that the answer isn’t that antidepressants, “don’t work.” Rather, it’s because of the variability in individual reactions and also the mechanism of co-modulation (which can take 4 to 6 weeks for the system to equilibrate) that produces the frustration that people have with antidepressants. Hope that helps, somewhat.

34

SSRIs don’t work on me. Or to be more precise, they do a little good for a while, then they stop having any positive effect and leave me with nothing but unpleasant side effects.

Personally, I’ve come to the conclusion that I’m better off without the side effects and trying to cope with my illness drug-free. I know other people that have come to the same conclusion. They might well be life-savers from some (and I’m not disputing that) but they do very little for others, including me.

35

I think at some point, probably a few decades from now, people will look back at this era of psychological treatment with shock and dismay - much like we look back now on drilling holes in people heads and cutting out pieces of their pre-frontal cortex as being barbaric and effective for the wrong reasons.

It’s amazing, in a disturbing way, to see how brainwashed people are regarding the current state of mental disorder treatment. Look at the people in this very thread, so assuredly stating they don’t have placebos. No one said you do, it’s the effect. I’ve been on three types of anti-depressant, and there is obviously no way the medications are placebos - clearly they have effects on your mind and body.
What is being referred to by this article is the effect only - based on the belief that you’re taking medicine to help you get better, you get better - nevermind what it is you’re physically putting in your mouth.
However from what people are saying here, it’s clear they’ve convinced themselves - perhaps out of sheer desparation, and who could blame them for that, that the medication is the answer, the only answer, forever and ever, amen.

36

I’m not sure I believe this. Despite decades of depression drugs, the makers in the commericals still have to admit that they don’t know how they work (“antidepressants are thought to work by…”) so what makes you think it’ll be different twenty years from now?

37

Let’s put it this way: Suppose there was some horrible mix-up at the pill factory and it turned out that many patients who were told that they would be given prescriptions for potent experimental drugs known to help many out of depression (though unfortunately also often producing uncomfortable side effects) were accidentally merely given Ex-Lax for long periods? And suppose, furthermore, it turned out that among these patients, the rates for remission of depression turned out to be very high, to the point that large numbers of such patients gave ardent testimonials about their experiences with the drugs they were given and how it helped them get their lives back on track.

Since many patients would then be found to have gotten better after experiencing the markedly non-null effects of these drugs, and were willing to ardently testify that it was definitely the drugs they were given which were responsible for their turnaround, that the side effects were pretty powerful stuff but it was worth it in the end, etc., would it therefore be clearly, inarguably true that there must be some particular mechanism by which said drugs, in particular, were especially efficacious at treating depression? Would arguments like “A placebo broke my stomach? Hard to believe” provide sound support for such efficacy, and for the theory that depression was caused by a failure to properly regulate intestinal fluid levels, and so on?

Certainly, it would be a priori possible that such a theory were true. But, once the factory mix-up were discovered, I imagine most people, even most of the posters in this thread, would be skeptical. Probably, many would consider plausible the alternative theory “Well, maybe lots of patients got better on these drugs, not because of some hypothetical mechanism specifically linking a unique actions of these drugs to the ailment being treated, but perhaps for another reason. Perhaps even simply because some large fraction of patients will begin to spontaneously achieve relief from this ailment in any situation where they are able to easily maintain a hope that they are being given potent drugs which can help them out of their condition, regardless of most of the properties of the actual drug given”.

Well, how could you tell whether this was happening? You’d give a large number of people the Ex-Lax and a large number of people other, markedly different treatments (possibly even largely chemically inert treatments), trying as much as possible to make sure there were no unwarranted indications as to which patients were receiving which, beyond improvements in the condition being treated, and you’d see if the treatment efficacy was markedly different between the two groups. And if it wasn’t, you’d likely accept that the Ex-Lax, while truly working in many cases to relieve depression, were not actually achieving this effect by any mechanism above and beyond that equally available with alternative, even chemically inert, treatments as well.

Well, I’m not aware of any trial comparing Ex-Lax to other treatments in terms of their efficacy at relief of depressive disorders to other, as such. But I have heard of trials comparing traditional antidepressant drugs to so-called “placebos” for the same thing. What’s so different in principle about those trials?

38

And, just to make sure no one takes me the wrong way, I don’t claim to know whether or not traditional antidepressant drugs really are specially efficacious at treating depression. My point is not that this theory must be wrong. My point is only that many of the particular arguments I see being advanced in defense of it in this thread are distressingly unscientific and unsound.

39

Hm. On re-reading the thread, there are rather more people saying “Maybe it is a placebo effect, but that’s good enough for me, so long as it works” and less people saying “Nuh-uh, there’s no way this could be a placebo effect, because it clearly works well for me” than I thought. I have no problem with what the former group is saying, so perhaps I’ve wasted everyone’s time arguing with a phantom audience of the latter group. Oh well…

40

I have been on many different antidepressants over the years - Trycyclics, MAOIs, and SSRIs.

In every case the medicine did relieve my symptoms of depression (sometimes immediately) for a few weeks but then just stopped working.

This makes me suspect that I was subject to a placebo effect or I was benefiting from the initial sedating side effects which soon wear off.