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.
For more in-depth videos related to neuropharmacology, subscribe to my channel!
IG: @neuropharmacist
Twitter: @samuelkohtala
www.neuropharmacist.com
---
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’
www.sciencemed...
Background on antidepressant research
helda.helsinki...

[@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 People get stuck on outdated knowledge and don't always keep up to new research in their field.

[@halphantom2274]

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.

[@drewwollin3462]

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.

[@afanasymarinov2236]

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.

[@Neuropharmacist]

Thanks!

[@profbri.02]

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.

[@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.

[@Neuropharmacist]

Depression is a complex and heterogenous disorder, and the general idea these days is that there are many subtypes characterized by varying symptoms. E.g. some have insomnia and others hypersomnia. Some benefit from this drug and some from that. Dopamine certainly is a key player, and sometimes, although rarely, patients are prescribed dopaminergic stimulants for depression. But I would not say depression has more to do with dopamine than serotonin, and I would certainly not say that depression is caused by any single neurotransmitter/modulator.

[@kalliaslands9938]

Not exactly as D2 blockers also treat depression. If you want to increase dopamine a partial agonist like abilify or vraylar might help. If SSRIs don’t work you might want to try something stimulating like Wellbutrin or a channel blocking medication like lamictal or lithium. If depression came down to just one circuit it would have been solved by now.

[@wazzuhathemorning]

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

[@jonathanberry9502]

🎯 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. Made with HARPA AI

[@FullMetalNobody]

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

[@profbri.02]

Absolutely!!! 👍

[@T3H455F4C3]

Like all the time?

[@zahraelhatt6657]

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.

[@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! 😊

[@Neuropharmacist]

Thank you!

[@angiebear8727]

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 👍

[@Wrongtree]

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

[@Neuropharmacist]

Happy to hear, thanks!

[@dynamicdavid]

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

[@Neuropharmacist]

Haven't looked into that.

[@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?

[@Neuropharmacist]

Haha sorry about that!

[@everything_doc]

Can you do a differentiation between SSRIs vs SNRIs?

[@profbri.02]

SSRIs increase levels of serotonin whereas SNRIs increase the levels of norepinephrine, a different neurotransmitter.

[@metalmaniac5218]

have red wine its good

[@Neuropharmacist]

The study that David Nutt refers to regarding the measuring of serotonin in depression has now been published: www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01704-8/fulltext

[@eaudesolero5631]

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.

[@eaudesolero5631]

we also do not even know what all the neurotransmitters in the brain are. nor what all the receptors in the brain are. also people can have more or less of one type of receptors in one or more parts of their brain. as well as people could produce more or less of a certain chemical. so that right there is 4 different options to consider.

[@eaudesolero5631]

we've all seen alot about chatgpt lately, and alphafold has been working on the protein folding problems for a years now. i recently saw a guy used chatgpt to put in all of his medical information, things that worked and did not worked, etc, lab tests and used it to help him cull through the worlds database, and it was able to give him an answer that actually helped him . i forget who or what it was, or maybe it was his dog. but the point is that with the complexity of the brain, the numbers of receptors, and medications, etc, and the severe lack of cohesion with bringing together all the data that has been generated about neuroscience in to one cohesive whole (which is the mission of Numenta by Jeff Hawkins in part) someone needs to do like that guy and leverage this emerging technologies to help with diagnoses and directing treatment options. who knows it may show us something about the brain that no one thought of and is completely overlooked.

[@eaudesolero5631]

And add to this the recent discovery that some people have certain enzymes and genetic markers that make some kinds of medication ineffective

[@annabellelee2201]

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

[@Neuropharmacist]

Thank you!

[@driggerfireon5760]

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

[@Neuropharmacist]

Great to hear!

[@rayjames3452]

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

[@missisipi9992]

Thank you!

[@missisipi9992]

I need treatment very much

[@afanasymarinov2236]

Go and get it, man!

[@missisipi9992]

@@afanasymarinov2236 where?

[@petercarlisle2927]

Thanks for the video. I was unsure if I should be taking some prescribed pills but I will now lol