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.

TRANSCRIPT:

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.

REFERENCES:

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.

[neurochallenged]

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 suffer from milder cases of depression). 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 this research.



Some studies that question the effectiveness of antidepressants are linked below.

[rabeealwan]

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.

[blippiwithaclippi]

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.

[mghtysaucE]

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.

[shayla]

Sometimes it doesn't take that long to feel the effects. I went from really low, dissociative, irritable to neutral, present, and not irritable within about two hours. Its day four for me and I genuinely can not believe the difference. I can't believe I didn't start earlier. And a reminder: taking antidepressants for depression etc is just like taking Panadol for pain or wearing a cast for a broken bone. It's normal.

[TurbinationE]

One of the few times where going down to the comments section was actually a good idea. I'm finally looking into antidepressants for long term mild depression after 5+ years, and the ending statement about "SSRIs might only work well for people with extreme cases" had me really worried, since I've never experienced total anhedonia or su1c1dal thoughts due to depression.

[ikesters]

I never realized I needed SSRIs until I finally said "f*** it" and took it. And for those who are afraid of the "why didn't I take this sooner" thoughts, (like I was), they don't really have any effect at all. In fact any negative thoughts you just stop believing because you see them for what they are, useless thoughts. You made them yourself, but you can easily destroy them. And this also goes for positive thoughts as well. And suddenly you really end up realizing YOU. ARE. IN. CONTROL. You can choose what you want to believe or not. That's my experience so far when I started taking SSRIs.

[marinaago]

I just wanted to give a word of encouragement to anyone thinking of starting this journey. It helped me massively and allowed to live a normal life, even have the strength to actually use other tools such as therapy that I would otherwise have no energy to do. Please don’t turn it down just because it’s a medication as it can turn your life around very positively

[ihlmzey]

I think your last comment about the placebo effect really does a disservice to these life saving drugs!! And it also turns away people who may be interested in taking them. They are powerful, amazing and life changing for many, many people.

[sarahbaldwin]

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

[choco]

I started off with 10 mg of Prozac and maybe it was a placebo effect but that first week I noticed immediately an increase in being present at work with little anxiety. Before Prozac, I had a lot of stuff going on in my life that it affected my memory especially at work where I’d end up getting in trouble for not following instructions.

After i started taking it, I felt more prideful in my work, I wasn’t in my head to the point where I finally started to relax, I became funnier because I was in the moment and didn’t care about my responses, I became more optimistic with my coworkers and even started calling out shots and being more involved. Tbh I honestly tripped out on how debilitating my anxiety was until I started with Prozac and it hasn’t been a full month yet of being on it

[geoben]

Prozac ( fluoxitine) has helped significantly for my depression/ anxiety. But be aware that after some time you may "plateau" on it. A point where it becomes ineffective. Talk to your shrink right away if that happens. A PSYCHIATRIST NOT a psychologist. A change in dosage or type of meds may be required. Also sunlight, natural light in the house helps a lot. Diet, eggs, salmon, B complex vitamins, green tea, red ginsing, omega 3, 6, and 9 oil capsules also help. (Nature Made at Costco.) It's extremely difficult for people who've never experienced depression/ anxiety to understand what you're experiencing. And a lot of them think they do.

[friedonions]

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.

[ElectricDanielBoone]

SSRI worked great for me. My problem was more along the lines of obsessive thoughts and control of my anger. What a relief! The drug made me super sleepy for about a week. I had no doubt something was changing in my brain! If I miss a few days I get some really odd sensations in my head too.

[mentalhelp]

I have just started my own OCD channel about my own struggles and I love what you have done its amazing. keep up the super work😀

[Ellen]

I’ve been taking Zoloft for about 5 years and I would not still be here without it. I had depression, and sever social anxiety, I could barely leave my house, I’m not 100% cured or anything it takes a lot more work then just going on medication to heal but without medication I wasn’t able to even begin getting better

[ellehoods]

When my life was much harder in my teens (I was Sui side hall from 12-18) there were a lot of traumatic events like homelessness, losing friends to sui side, unsafe people- in and out over time. When I was doing better financially in a safe place w good nutritious food- the ptsd would make it very hard to concentrate on school or life tasks. It took me a long time to figure out the right antidepressant but once I did I felt: way more capable, able to put down intrusive thoughts, more energetic and optimistic.

I was afraid of dependence, but as it turns out in the years I was taking it it open my tolerance threshold enough to learn healthy coping mechanisms and restructure abs replace my thought patterns. So, instead of defaulting to self loathing narratives when upset I had a roster of assuring statements I'd built for myself. So when im off anti depressants now I have much better mental health in general to the person I was before taking them.

I still go on and off (not frequently) and check with myself after a year or two if I'm in a place where I feel I need them or could benefit. If I think I'm doing fine I try out being unmedicated. Sometimes I'm able to do it for years at a time. I think as I grow up (I'm in my early adulthood, mid 20s) I won't use it as much in the future, and that progresses can't be taken away in my opinion. If I do continue meds again later on, I won't be ashamed for that. It's genuinely helpful in times of longer crisis for me.

[ToTheBridge]

been trying to figure this crap out for a while now and had a lightbulb moment watching this, thank you

[lovegyal]

Just started taking citalopram and can feel a difference. I’m not thinking to deep about negative things but I want something to help with my fatigue as well

[laurenm]

I have been taking an SSRI for the last 18 years or so. I’m 28. I don’t remember how I felt when I started taking it, but what I can tell you is that if I miss even a day or two I will notice.