The new antidepressant hypothesis

Being a science student and having studied antidepressants, I thought I knew how they worked or at least why people thought so but after a lecture on the history of their development, now I’m not so sure.

Originally, in the 1950s-60s the thesis was that too many Monoaxamine Oxidase neurotransmitters (MAOs) such as serotonin and norepinephrine, were being oxidised by the brain. This led to a deficiency of them and thus depression. Drugs were developed to maximise the amount of MAOs in the brain, by preventing them from being oxidised. The idea is that high levels= better communication= stronger mood regulating circuit. The results were good! They appeared to work, yet serious side effects were often seen.

In order to reduce side effects, a new hypothesis was developed. The serotonin hypothesis. The idea was too much serotonin was being taken up by presynaptic neurons in the brain leading to a deficiency and ultimately depression. People, therefore, speculated that altering the level of serotonin would alleviate the symptoms of depression. This is where SSRIs were developed. They act by stopping the reuptake of serotonin and increasing the levels of it in the brain. Again, they appear to work. SNRIs do the same thing but for serotonin and norepinephrine.

The basis of these theories was PURELY SPECULATIVE. No one has been able to prove them. Though it could be argued that new research does exactly that, but this would depend on who you talk to.

Irving Kirsch showed that for people who’ve been on SSRIs before and experienced the side effects, if they’re then given a placebo drug with the same side effects, it appears to work. In his study, there was no significant difference between an active placebo (with side effects) and SSRIs. Yet, many people have criticised his work.

Studies have suggested that; changing serotonin levels in a healthy individual doesn’t cause depression, attacking symptoms of depression with SSRIs is no better than with an active placebo, and the placebo effect is critical in treating depression. Furthermore, one popular antidepressant bupropion appears to reduce depression in some people but it has not impact on serotonin at all, but dopamine and norepinephrine.

Obviously, though, I couldn’t just accept all of this to be true because I have seen antidepressants work, hell I’ve even FELT them work at times. In my day to day life I have yet to come across a pill that makes me feel ‘not depressed’ but I know that when I’m at my worst, medication is the only thing that can pull me out of it. So I turned to doctor google.

Apparently, there is this other theory that antidepressants cause neurogenesis (birth of new brain cells). This could explain why ADs take a while to work in the brain (whereas if it were just the amount of neurotransmitters you would expect them to work right away) because they are altering the pathways in the brain. I was drawn to how lots of these studies list physiological and psychological stress as a causal factor because it reflects the idea of early mad doctors, that neuroses were caused by stress. However,  it’s not a foolproof theory because some AD studies show neurogenesis and some don’t + it could be unrelated to what ADs actually do. Yet, it’s still really interesting.

I refuse to believe that antidepressants don’t work, but maybe they don’t work the way we think they do. Or maybe they do and we just happened to stumble upon the MAO idea by accident without having a clear reason for why this is the case.

What is your personal opinion and/or experience on antidepressants?




One thought on “The new antidepressant hypothesis

  1. ADs definitely do something. They are not the same as a placebo. I’d look to see if those studies have been confirmed and duplicated (or more) by multiple people. That doesn’t happen these days sadly, for many reasons. They are life saving for some people, literally. I don’t believe a placebo can effect that kind of change when someone’s chemicals are imbalanced. Restricting food, as in anorexia, causes a loss in serotonin in the gut which leads to depression as well as a host of other problems. It takes a while to be renourished so ADs are a great way to help until that happens. It gets the person to a place where they can deal with the emotional side of recovery until their body can catch up physically.

    As for me…. I can’t take ADs. They cause mania in people with bipolar 1, like me. It’s definitely not a placebo effect. I was periodically going manic and didn’t know why till they, researchers, realized this. What a relief! I take a mood stabilizer for bipolar depression now. I have a couple BP-1 friends who are on ADs and are constantly trying to stabilize their manic episodes. I wonder about their psychiatrists and if they ever read current research, grrr. Fortunately I have a very good psych who is up to date with everything BP-1.

    ADs have also been shown to help people with chronic pain. I have chronic pain but can’t, as mentioned, take ADs. I recently started on a mood stabilizer for bipolar mania and may or may not have had a placebo effect since it also lists that it decreases pain. However, the nature of chronic pain is that it will seep back in no matter what, at least for me. As an aside, when I am using anorexic behavior, my pain decreases significantly. It is because I am in a constant fight/flight/freeze mode making adrenaline a constant. When I recovery, I relax, the adrenaline goes down and pain comes back. I just started this medication (first stay at the ED program in Feb/Mar) and found pain relief but then I never fully recovered and used behavior increasingly which ended me up back in the program mid last month so I suspect it wasn’t the medication or a placebo effect but, in fact, the adrenaline. Why? My body is not fully recovered but I have been eating for a month and the pain is most definitely back.

    ADs work for many things. For some there is a placebo effect but how long does that effect last? I suspect not long where as ADs work over the course of years. My opinion? Who cares how it works as long as it does. 🙂


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