2-Minute Neuroscience: Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the most widely-used treatment for depression, and have been since their introduction to the market in the late 1980s. They were formulated based on the hypothesis that depression is due to low levels of the neurotransmitter serotonin. In this video, I discuss how SSRIs work, along with some questions that have been raised about the serotonin hypothesis since the introduction of SSRIs.


Welcome to 2 minute neuroscience, where I explain neuroscience topics in 2 minutes or less. In this installment I will discuss selective serotonin reuptake inhibitors, or SSRIs.

SSRIs were developed in the 1970s with the goal of treating depression by increasing serotonin levels. This goal was formulated based on the serotonin hypothesis of depression, which suggests that depression is caused by low levels of the neurotransmitter serotonin.

SSRIs work by inhibiting a mechanism called reuptake. In reuptake, a protein called a transporter transports excess neurotransmitter molecules out of the synaptic cleft, usually back into the neuron that released them. SSRIs inhibit the reuptake of serotonin.

By inhibiting the removal of serotonin from the synaptic cleft, this causes levels of serotonin in the synaptic cleft to rise. These increases in serotonin levels have been hypothesized to be the mechanism by which SSRIs can treat the symptoms of depression.

There are reasons now, however, to believe that there must be more to the mechanism of SSRIs than just changing serotonin levels. For example, when someone begins taking an SSRI, they generally have to wait about 4 weeks before their symptoms improve. Evidence suggests, however, that their serotonin levels rise as quickly as within an hour after taking the medication. Thus, it seems likely that SSRIs may affect serotonin levels, which then leads to other effects that influence the symptoms of depression.

Therefore it’s probable that more than serotonin levels must be changed for SSRIs to work, which suggests that depression isn’t caused only by low serotonin levels. Additionally, evidence has now emerged that questions the effectiveness of SSRIs. Some research has found they do not work much better than placebos, and may only benefit those who are most severely depressed, which is a minority of patients who actually take the drugs.


Invernizzi R, Velasco C, Bramante M, Longo A, Samanin R. Effect of 5-HT1A receptor antagonists on citalopram-induced increase in extracellular serotonin in the frontal cortex, striatum and dorsal hippocampus. Neuropharmacology. 1997 Apr-May;36(4-5):467-73.

Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008 Feb;5(2):e45. doi: 10.1371/journal.pmed.0050045.

63 komento:

Neuroscientifically Challenged
Neuroscientifically Challenged:
Please note that with the last 2 sentences of this video I’m not making a claim that SSRIs don’t work. Instead, I’m pointing out that some research has questioned their effectiveness, especially in certain individuals (like those who are not severely depressed). It’s not a statement of opinion that this type of evidence exists---it’s a fact that multiple studies have failed to find a large clinical benefit to antidepressants over placebos, at least in some groups (I’ll include links to several studies below). I was trying to provide a more complete picture by mentioning these studies.

I was not, however, trying to make any statements one way or another about the effectiveness of antidepressants. There is a lot of evidence to suggest that they do work, but the area is somewhat controversial. My own opinion is that the effectiveness of an antidepressant probably depends on a number of factors like genetics and depression severity, so it’s difficult to make blanket statements about how well the drugs work for everyone in the population. But there is evidence that some people benefit significantly from the drugs. More research will probably provide us with a better picture of who stands to benefit the most from taking an antidepressant.

Starting Zoloft a year ago was one of the best decisions I’ve made. My anxiety is more manageable and my depression is practically nonexistent.
Rabee Alwan
Rabee Alwan:
I started lexapro around 2 and half months ago. honest to god the best decision I have ever made. my anxiety was debiitating and I just couldn't control it anymore. it took me 7 Years to finally give it a shot.
Carly Maclennan
Carly Maclennan:
Me watching this after my second day of zoloft: 👁👄👁
Odelette Blue
Odelette Blue:
I don't know, I had a really bad odd ocd and it showed a bit of improvement as soon as I took my ssri meds..
now this got me overthinking and wondering if my meds are actually gonna work 👁👁
I would argue that SSRIs only really work when the depression is induced by (or worsened by) anxiety.
I recently got on an SSRI and I was wondering what was placebo and what was the meds. My depression got to the point where I was having constant anxiety attacks and it seemed to start to get better within a few days.
Zerxyo Sánchez
Zerxyo Sánchez:
Such an interesting issue!
Derek 162
Derek 162:
I am castrated and stripped from my emotions at 17 years old
Sophie Wembridge
Sophie Wembridge:
been trying to figure this crap out for a while now and had a lightbulb moment watching this, thank you
When serotonin rises in the synapse, serotonin receptors recede leading to the 4 week effect of SSRI's
John Smith
John Smith:
I remember reading this in Time magazine at least ten years ago. The article made the case that for most people any relief is placebo effect.
L D:
Thanks :)
Thank you!
Such a helpful and nicely short video. Talking about the transporters really helped. Thank you!
Thanks for explaining reuptake and blocking clearly and succinctly
If you have depression take mushrooms simple 😇🍄
Why are some of them significantly more effective than placebo for ocd though?
Batool Samen
Batool Samen:
Thanks ✌
Ψίθυρος -Ονείρων Παγίδα-
Ψίθυρος -Ονείρων Παγίδα-:
great work! thx a lot :)
Chuck Hickl
Chuck Hickl:
Not very informative for those of us on SSRIs and struggling with the side effects. Can you suggest a more informative video of yours on this topic?
I always had insane anxiety growing up. Didn't even know what it was called, I just always had stomach aches and sweaty palms. When I started taking Zoloft, it took a month or so like they said, but I have never felt this great in my life. I wish I started taking them during high school.
It could be 1 minute neuroscience if you pause every 10 seconds
Child Of wrath
Child Of wrath:
You have no idea how much this video helped me, My doctor was not well at explaining and have no been able to find anything that explained easy as this.thank you
Sunil Gupta
Sunil Gupta:
Incomplete knowledge about mechanism of action. SSRI do works. It is the desensitisation of 5HT1a presynaptic autoreceptors that explains the lag effect of SSRIs, which takes 3-4 weeks.
Brett Bjornson
Brett Bjornson:
Why due SSRIs have so many side effects to them?
Boban Bkc
Boban Bkc:
Getting off these narcotic drugs will cause you depression even if you never had it before. They should be banned.
Jordan Ash
Jordan Ash:
Maybe it's an imbalance of neurotransmitters at the synaptic cleft of neurons, or maybe it's the debilitating mindset of "there's something wrong with me and I can't push through these rough emotional times."

The emotions are real. They are powerful. But they are not bad. They are not unmanageable.

There's nothing wrong with you. You may have a disease of the blood, heart, be missing limbs, etc. But at a fundamental level, the level of the individual/soul/consciousness, there's NOTHING wrong with you. There's nothing wrong about the way you perceive reality.

You feel emotions that seem overwhelming. But you are in control. Sometimes they do overwhelm us, the emotions, desires, etc. But we are in control.

Deep down, we are okay.
SoCal Brooke
SoCal Brooke:
I just found your channel. Hoping you have some info on SSRI's and anxiety.
Jacob Huggins
Jacob Huggins:
I was trying to see if you have a similar video, but for how SNRIs work. Is there much of any difference in the way they work? They inhibit reuptake of norepinephrine, but what about the Seratonin? And what about the norepinephrine in the case of SSRIs?

I had tried Zoloft, but I didn't sleep for 3 days straight so I had to come off of it. Every time I would fall asleep I jolted awake with a body spasm, no matter how tired I was. Countless times each night. Now I am starting on an SNRI to see if my body handles it better. I am trying Effexor, granted I am worried about all the side effects and withdrawal/permanent withdrawal symptoms some people have. Maybe I'll decide to just continue in anxiety and not go through all of this stuff as i'm currently feeling shaky/off with my first dose of Effexor I took this morning.
Dennis Rue
Dennis Rue:
Key word hypothesized
J.A drew
J.A drew:
Do they help against IED?
I'm on day 3, I can't stay awake. Also my head feels overpressured like a balloon ready to pop.
So you end up with less serotonin day after because reuptake was blocked and not stored back (after synaptic cleft is empty)?
Amil Naim
Amil Naim:
Pm ssri
Lorelei Haart
Lorelei Haart:
I took Cipralex for 2 months and it didn't have any effect on me. I'm glad I stopped and I'm feeling better now just with exercise and herbs like Saint John's wort and lemon balm. I take 5htp and melatonine for sleep. Your intentions are also very important. You have to want to move away from the depressed state and start implementing small gradual changes in your life.
Ya Ya
Ya Ya:
Do you have a video on how opiates affect the brain? And, what happens neurologically when one withdrawals from opiates? I think it would be a great tool for people in rehabilitation to have easy to understand physiological effects of each..☺️
Hong Liu
Hong Liu:
Great video on the current hypothesized mechanism of SSRI! This is the only video I FOUND that goes beyond the old hypothesis of increase serotonin in synapse is what leads to treat depression and anxiety. Thank you!
Just dropped it feel much better and very tired before bed
Mega Hawk
Mega Hawk:
Is chlorphenamine maleate used as antidepressant since it have activity?
Maryland Guy0326
Maryland Guy0326:
I was put on 50 mg Sertaline 2 weeks ago. Hope I didn’t make a mistake by taking it
Rob Luker
Rob Luker:
I took one yesterday and I dont feel like myself at all I hate it not going to take it anymore
Ajay Singh
Ajay Singh:
I have a question -

Are reuptake transporters and autoreceptors the same thing ?
Is there anything in nature that inhibits reuptake of neurotransmitters?
Gizlan Abbas
Gizlan Abbas:
I have a question, what is the 'bad version of the gene of serotonin?
Does it guaranteed that there would be depression or does it results in far more cases of depression if there was a history of stress?
I have bad OCD and I just started with Fluvoxamine (Luvox), I am on my third day but I can already see a difference
I took one Lexapro, prescribed to treat ADHD, and it made me SO sleepy and lethargic. I couldn't wait for it to leave my system. I don't know if I should give it a shot maybe for a few days, or if it's just not right for me. So far NOTHING that's been prescribed for me has worked: Adderral, Lamictal, Trazodone (to sleep), now Lexapro. I get the feeling that all doctors do is throw medications at you in an experiment basically to see if something works. In my case, EVERY single one has made me feel horrible.
Justas Mackevicius
Justas Mackevicius:
paroxetine kicks in a couple of hours and not weeks. it works wonders if you're depressed or anxious.
Cosmic Cola
Cosmic Cola:
To anyone who ever sees this. When I started anti depressants 7 years ago, it was an SSRI. I was one of the people who noticed a change within an hour. I went from an immense TERRIBLE depression, to finally having clearer thoughts that weren’t about death and hopelessness. Please don’t discount medication. It is often the right catalyst you need.
Just started lexapro yesterday. Immediately noticed the sexual dysfunction part of it on day 1 about 5 hours later via self stimuli. I did not need weeks to notice it interacting with my brain; it has lifted my depression and in less than 24 hours which is pretty crazy; then again I'm a small guy and fast metabolism. But, so far the anxiety is still about the same-- I know. Probably needs more time. Initially it made me tired as hell (took it around 6pm). It then kept me up until 5am not unlike tripping on something just no visuals so... if you start on SSRI's, you may wanna consider taking them in the morning; especially if depression has been leaving you with interrupted sleep as is. It kinda reminds me of an LSD come up just without it continuing to intensify or the psychedelic effects. The butterflies in the stomach feeling is identical however.
Oregano oil natures SSRI "Our data suggest that carvacrol is a brain-active molecule that clearly influences neuronal activity through modulation of neurotransmitters. If regularly ingested in low concentrations, it might determine feelings of well-being and could possibly have positive reinforcer effects".
Build sexual arousal defeat the enemy
Build sexual arousal defeat the enemy:
SSRI Works same like cocaine with Dopamine.
I hate all these Drugs !
Trigger Happy
Trigger Happy:
the video makes it kind of confusing to understand. basically the proteins which trap serotonin are inhibited , so a larger concentration of it is present , which is believed to help depression. people with depression are believed to have a lack of serotonin production for unknown reasons , so this is the best method of treatment for now until scientists can discover more. neuroscience is incredible, and has the potential to make people happier, healthier and more aware.
i take 75mg day of Zoloft (Sertraline) and 15mg of Zyprexa (Olanzapine) everyday since 2004. I have treatment resistant depression.
xVeNoM 757x
xVeNoM 757x:
SSRIS lower serotonin, causing more depression. Doctors are literally making things worse by prescribing them. Just because something makes you feel better once or twice doesn't mean it's good, in the long run. Cold showers are better. Also 5htp.
Rae Sanders
Rae Sanders:
Great instruction! Wish was longer! Is the reuptake blocked by blocking the action of the serotonin transporter protein, orrr?
Hilary Forgie
Hilary Forgie:
Do they cause low dopamine levels?
Paul ES
Paul ES:
I appreciate this effort, but I don't know why such videos insist on being delivered at such a fast rate. Do you really need to talk that fast? Are you afraid your audience can't invest, say, THREE minutes to understand this important concept.
Further, tho' I know lots of folks aren't trained speakers, if you make another video, pronounce your words more clearly. For example, "synaptic cleft" came out as "snaptic cleft," which is largely incomprehensible if you don't already happen to know the words "synapse" and "Synaptic." I see this everywhere; people. in their specialized field forget that their audience may not know what the speaker is referring to. So a listener might think, "What's a sneptikclefkt?"
In a teaching./instructional video, always assume your audience knows nothing and work from there.
Thank you, tho', for providing this. It was helpful.
Always Flying
Always Flying:
I tried all kinds of ssri drugs and nothing helped with my anxiety and OCD. I started taking a product called 5 htp and it has helped me beyond words. If you are low in serotonin you need to make it not recycle the little that you have. Do your own research and see your yourself

Edit forgot to mention that serotoin is made in your stomach as well. Balanced diet and supplements work far better than pharmaceutical drugs

Hope I help at least one person
Prashant Kumar
Prashant Kumar:
Take Brahmi medicine which is Ayurvedic. It will calm your mind and improve memory. It also decrease your overthinking.
Henry Morgan
Henry Morgan:
Although though SSRIS are effective for some people, for many they are not.

MAOI INHIBITORS, such as Phenelzine, are much more powerful than SSRI's- They not only interact with the Serotonin neurotransmitter, but also with the DOPAMINE (very important) and Norepinephrine neurotransmitters. They have the highest efficacy of all antidepressants for depression, social anxiety, etc.

MAOI Inhibitors are heavily under-utilised by psychiatrists due to their outdated dietary requirements and the fact that they are not patented (unprofitable).
For accurate and non-biased information on Maoi inhibitors please look at Dr Ken Gillman's website through this link- https://psychotropical.com/

Please spread the word so we can save lives!
Yeah thanks for the drugs there now I'm anxious, horny, drinking like a fish and feeling spaced out. I don't like it. I'd rather eat oxy or hydro at least those feel good. Wake up people! your feelings emotions and thoughts have nothing to do with chemicals in your brain and everything to do with reality. If my thoughts are nothing more than chemicals then I'm going to eat drink and be merry until I die. There's no love just chemicals. There's no hate just chemicals. There's no thoughts just chemicals expressing themselves. What a store stupid worldveiw and now I'm being force fed these drugs and I can tell they are messing with me. I'm going to have to start keeping my bottle of water on me at all times and eating only out of cans i already know it. And buy my kratom in a cealed package. I don't want this stuff in me and it's against the law and you're violating my rights by forcing tricking me. I want nothing to do with anyone I want this crap out of me