Is the Serotonin Theory of Depression DEBUNKED?

The serotonin hypothesis (or in popular terms, serotonin theory) has been an influential idea since the discovery of the first antidepressant drugs in the 1950s. A recent review article has supposedly debunked the idea that serotonin has anything to do with depression. In this video, I will give my pharmacologists perspective on the topic.

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IG: @neuropharmacist
Twitter: @samuelkohtala

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Additional reading:

The serotonin theory of depression: a systematic umbrella review of the evidence
PMID: 35854107 DOI: 10.1038/s41380-022-01661-0

Expert reaction to a review paper on the ‘serotonin theory of depression’

Background on antidepressant research

[francoisstrength]

I've noticed the younger the doctor the better the treatment these days. People get stuck on outdated knowledge and don't always keep up to new research in their field.

[halphantom]

I can only say from my own experience, that SSRIs didn't work for my problem with depression (tried 3 different ones). It did something. Shifted the basic mood slightly to the positive, but my main problems weren't affected and I suffered from the side effects. Felt like it mainly affected the serotonin in my guts, as I had to constantly look out for a toilet. It turbocharged my digestion and altered how my body handles its fluids - dry mouth, dry eyes and dry nose with in worst case nosebleed. Seems, all the fluids ended up in my degestive tract. In the end the downsides weighed out the positive effect. You don't get cured from depression with the constant threat of shitting your pants.

[jonathanberry]

🎯 Key Takeaways for quick navigation:

00:12 🧠 *Introduction to the Serotonin Hypothesis*
- Explanation of the serotonin hypothesis of depression.
- The recent review article by John Moncrief challenging the serotonin theory.
- Headlines and reactions from the scientific community and media.
- Overview of the serotonin hypothesis of depression.
- Mention of John Moncrief's systematic review.
- Media and scientific community's reactions to the review.
03:06 🕰️ *History of Antidepressant and Monoamine Research*
- Development and introduction of the first antidepressant drugs in the 1950s.
- The monoamine hypothesis and its influence on the development of antidepressants.
- Emergence of selective serotonin reuptake inhibitors (SSRIs) like fluoxetine.
- Introduction of first antidepressants like iproniazid.
- Influence of the monoamine hypothesis on drug development.
- The commercial success and development of SSRIs.
05:45 📉 *Contrasting Evidence Against Monoamine Hypothesis*
- Growing evidence challenging the monoamine hypothesis.
- Emergence of new neurobiological clues and hypotheses.
- Refinement and evolution beyond the simple monoaminergic neurotransmitters.
- Research findings against the monoamine hypothesis.
- Introduction of new ideas like neurotrophin hypothesis and network hypothesis.
- Shift in focus to understanding antidepressant effects beyond monoamines.
08:11 🧬 *Neurotrophin and Network Hypotheses*
- Exploration of the neurotrophin hypothesis emphasizing neurotrophic signaling.
- Discussion of the network hypothesis focusing on neural network adaptations.
- Role of neurotrophic factors and plastic-related signaling pathways in depression research.
- Explanation of the neurotrophin hypothesis and its basis.
- Introduction to the network hypothesis and its emphasis on neural plasticity.
- Mention of the importance of neurotrophic factors in mood regulation.
10:23 💊 *Expert Opinions and Controversies*
- Discussion of expert opinions on the serotonin hypothesis.
- Perspectives from Professor Gitte Knudsen and Professor David Nutt.
- Criticisms and responses to the review by Dr. John Moncrief and Dr. Mark Horowitz.
- Insights from leading neurobiologists on the complexity of depression.
- Critique of methodologies and findings presented in the review.
- Consideration of the broader implications and controversies surrounding the serotonin hypothesis.

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[drewwollin]

Very good overview of the approaches to antidepressants over the years. I read the paper and thought it simplistic and not very valid methodologically. I didn't know the authors and checked their background only to find they were mainly psychologists writing in an area they have little expertise. It is a pity that there is such a turf war between psychology and psychiatry. No single approach is completely effective. As you point out, there needs to be a range of treatments for such a complex disorder as depression. Again, well done.

[afanasymarinov]

Being a senior physician in psychiatry and a researcher in the mental health field I appreciate your videos so much. Thank you for providing clarity on this contentious topic. Some critics of pharmacological or other somatic treatments in psychiatry are throwing out the baby with the bathwater, in turn harming many vulnerable patients.

[profbri.]

11:41 yes, of course we do. Given the negative side effects associated with the use of many antidepressant drugs, we most certainly do want to know how, and indeed, whether they work at all.

[DrSyl]

This is an excellent and sensible review of the history and evidence. Well done mate. Only a matter of time before your channel blows up!
I might make a video about this and if I do I’ll definitely do a shout out to your channel! 😊

[Wrongtree]

Well done, Instructive and informative! Hope you get the recognition you deserve

[everything_doc]

Can you do a differentiation between SSRIs vs SNRIs?

[angiebear]

As someone who has suffered from boughts of depression/anxiety since early childhood ty very much for taking an unbiased look at this study. Have always thought some sort of genetic imbalance made sense since my Grandmother, Father, and many close relatives have similar issues but what do I know? Lol. Again ty for explaining so eloquently and understandable the effects of medications on the brain and how certain hypotheses were reached. New subscriber 👍

[gskcsc]

Antidepressants (medicines) are like friends on whom we should not completely depend on.

[ChrisfromGeorgia]

I'm not college educated in this topic, but I think it has more to do with dopamine than seratonin. Just look at addiction. Addict's self-medicate to relieve their symptoms. What do mostly all street drug's highly increase levels of? Dopamine. Honestly, I have had depression for the majority of my life. Personally, I have tried a many SSRI medication's. They only made me feel worse. This is just my opinion from what I've experienced and witnessed. Thank you for this video.

[IndelibleAndy]

Did anyone else have to rewind 17 seconds at 6:04 because you kept getting distracted watching the male finger failing to mansplain something to the female finger in the stock footage?

[zahraelhatt]

It's interesting however this may be anecdotal but i know a few people not satisfied with their treatment and side effects. Especially i would worry if i would have to take meds long term or can there be a cure. I think this is kind of important to understand the distinction.

[annabellelee]

This is extremely well done, very helpful, excellent sources, and well explained. Thank you! Subscribing now!

[FullMetalNobody]

If everyone was on shrooms, Nobody would be depressed. 😅

[dynamicdavid]

Any Opinions on METHYLENE BLUE? ...Excessive doses can lead to “Toxic Serotonin” Yet mild doses are Very helpful to depression and Also Nootropic.

[eaudesolero]

good balanced overview thanks. .. some people have not caught up with the times and new research. some people have fixated views regardless. some people have their ideologies they want to push. some people have their own emotional triggers, blind spots and bad experience, etc ... and alot of people will only look at or talk about 1 thing without regard for anything else connected and relevant. it's a real problem in this society in general.
depression is more of a description of symptoms as far as i see it. and it could have many different underlying factors depending on the person being affected. some people get some relief with some medications, others do not. there is a large number of people who do not, and that is why people are arguing and fighting against all the ideas that people are pushing. because there is obviously something not being effectively addressed. and there is no good method of scientifically and logically determining which might be the correct one. they just start prescribing things to see if any of them do anything.
come on seriously, we need more concrete methods. we need to use fmri, spect, or what ever for diagnostics. we need to be able to measure levels of neurotransmitters in the brain.
depression has also been called learned helplessness. which could point to the dopamine reward system.
i've dealt with major depression 3 times in my life. each of them were the result of a loss of love. physical pain actually resulting, it literally hurt. very stressed, trouble sleeping, lots of crying. smoking cigarettes helped. i got through the first ones after some times, 6 months to a year, without medication etc...
the last one has been an ongoing fight because it has to do with custody of my daughter and an ignorant and biased system and continued alienation. i've tried at least a dozen medications. none of them worked. serotonin and dopamine. tricyclic. (nuero)epinephrine, etc ... none of them helped with depression, anxiety, or insomnia. no talk therapy either. actually that made it worse.
but one thing i find that i have wanted/needed that makes me feel better is when I'm around my daughter, on the little occasion that i am, and we can play, and hug each other. that is oxytocin. there has been little research done as far as I've found. but i've seen oxytocin related to the positive effects of psilocybin. it is an area that needs significantly more research. and there are no medications that i know of that work with it.
i did find some relief in an atypical that is no longer available in the USA, tianeptine sulfate. it was like taking a long deep slow breath that calmed my thoughts, relaxed me, and allowed me to sleep. i never had any negative effects from it. but its method of action is not known as far as i've been able to find. so that could point to stress and inflammation. i'd like some thing that simply reduces the production of the stress hormone. that is also implicated in gastrointestinal problems associated with alof of people who are experiencing, ptsd, anxiety, depression, insomnia, and cluster b. but i do not know of anything that does that either.
and we have not even talked about the glia. but there is alot of talk about how important they are in their supporting roles.

[DrIIGerMusic]

Very good and balanced perspective is offered. Exceptionally well presented.

[rayjames]

Thank you, that helped me understand the issue much better.