Since SSRI raise serotonin levels almost immediately , why isnt there an immediate effect if depressed people lack serotonin ?
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I’m not a doctor but my understanding is that our brains have plenty of serotonin transporters to start with so it takes a while for your brain to create more transporters. The additional serotonin is there but it’s not effective until your brain figures out that it needs more taxis to get it where it needs to go. It’s not effective until the serotonin arrives at its destination. In the meantime before this happens, the extra serotonin is not used.
It doesn’t raise serotonin levels immediately. It stops your neurons from re-up taking the serotonin that is normally produced. Over time it can then build up.
It’s not actually well understood. Presumably the drugs create some immediate new conditions in the brain, which causes gradual adaptive changes in the brain, and it is this slower brain reaction to the drugs that may lead to symptom improvement, rather than some immediate direct effect of the drugs on depression.
While we do know that SSRI’s help a range of disorders and illnesses, we don’t know exactly why. We also don’t exactly know what causes depression.
SSRI clinically significant effects aren’t due to increasing serotonin, they’re due to epigenetic changes in our DNA in response to increased serotonin. Precisely how this works isn’t well understood.
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Short answer is we don’t know for sure. But the theory is it takes 8 weeks before new neural connections are formed and this is thought to be the cause of the antidepressant affect. Ketamine seems to do this too but much more quickly. But still just a theory so far.
It’s almost entirely a myth that depression is linked with serotonin. There’s very little evidence to support that claim and it’s typically of bad quality. SSRIs themselves are the main evidence implicating serotonin in depression; we know SSRIs increase levels of serotonin AND that SSRIs help depression sometimes, so we made the assumption that depressed people lack serotonin. But we do not fully understand depression nor do we fully understand SSRIs. They’re very new drugs and the research on them is highly obfuscated due to the large amounts of money generated by them and monetary ties between researchers and pharmaceutical companies.
One theory I’ve read is actually that SSRIs take so long to work because they’re causing the person to essentially build a tolerance to serotonin. Some victims of suicide have been found to have an unusually high density of 5-HT2C receptors, and it’s hypothesized that chronic overstimulation by the increased levels of serotonin leads to downregulation of these receptors over time. It’s similar to how most other drugs start losing effectiveness over time as you build a tolerance.
Psychiatrist here: (but notably, my job/training is diagnosis and treatment. I am not a researcher dedicating my work to understanding how these meds work in the body. If there is someone here like pharmacist or psychiatrist/PhD,etc, please check my ass.)
There is a lot to unpack here, all of these answers are part of the answer.
1) Ultimately, we don’t FULLY understand how SSRI’s cause their effect. At this point, we certainly know that depression is FAR FAR FAR more complicated than *just* serotonin deficiency.
2) Yes, SSRIs do increase serotonin in the synapse very quickly (few days), but we know this isn’t the full explanation because of the same reason you’re asking this question.
3) we Believe part of the answer has to do with (as someone else posted here) has to do with receptor sensitivity, as well as impacting how the genetics in neurons is read (transcription levels) to produce the proteins that work with serotonin. This explanation partially would fit with why it takes a few weeks for the meds to work.
4) for several reasons (I can’t recall details off the top of my head), we believe that the benefits of SSRI’s are beyond just the impact on serotonin. Some of the general ideas that are likely related and being researched include neuroplasticity (brains ability to trim old connections and make new ones) and Brain-derived Neurotrophic Factor (BDNF), which has to do with inflammation of the brain.
5) *shrug emoji*
6) please check my ass.
I’ve been on multiple SSRIs over 20 years. A few of them take effect immediately for me when starting. A few took a month. You always hope it’s gonna be the first, especially when you are desperate.
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