I understand that 5-HTP and tryptophan are pre-cursors of serotonin and are sometimes used to treat depression. But common treatments involve selective serotonin reuptake inhibitors (SSRIs)
This seems backwards to me. Why inhibit reuptake rather than boost the serotonin level? Can we not manufacture Serotonin? Or can it not be properly absorbed?
The naturally-occurring stuff isn’t being absorbed properly – so adding more isn’t going to change that; what you need to do is make sure that what’s there is utilized properly, which is, apparently, what the SSRIs do.
The nerve impulse in the brain travels from the “terminal button” of one nerve process onto the dendrite of another because the terminal button dumps a lot of neurotransmitter into the gap between them (the synapse), and the neurotransmitter excites the dendrite into carrying the message along. After dumping the neurotransmitter into the synapse, the terminal button sucks the neurotransmitter back in, so it can be used again later. This is “reuptake.”
Many people with clinical depression don’t have enough of the neurotransmitter serotonin. Nerve impulses are passed along more weakly than they should, or aren’t passed along at all.
SSRIs, selective serotonin reuptake inhibitors, stop the terminal buttons from sucking so much serotonin out of the synapse and back into themselves. This extra serotonin hanging around in the synapse makes nerve impulses travel more easily and more strongly. This, in theory, relieves some symptoms of depression.
Did that answer the question?
Maybe. But if so, I’m not yet following.
You described it as I understood it.
My question: Rather than prevent reuptake, why not provide *more *serotonin?
Wouldn’t that provide extra serotonin for the synapse?
Not to put too fine a point on it but from my understanding and (I think) from your explanation:
1: After using Seratonin the brain sucks it back in. (reuptake)
2: Low Serortonin levels are thought to contribute to depression
3: SSRIs prevent the serotonin from being sucked back in
My question, rather than prevent it from being sucked back in, why not provide more?
To tell the truth, I don’t know the factual answer. My two best guesses (as a person with an unused but fairly recent degree in neuroscience, but not in pharmacy) are:
Because forcing the brain to make more serotonin would upset its chemistry, which, even though “broken,” is still natural. The SSRIs don’t change the amount of chemicals in the brain, just their distribution… which sounds, to a coward (or a humble man), like a better way to go about things.
Also by increasing the amount of serotonin hanging around in the synapse, you get a similar effect to what you would get just by increasing the amount of serotonin in the brain. It’s only important when it’s in the synapse–and SSRIs increase the amount in the synapse. This works for a lot of people, so the question of using a different drug with a different effect doesn’t come up.
I wonder if providing more would be less sustainable than inhibiting reuptake. There are plenty of illegal drugs that IIRC raise serotonin levels, however, there is a chemical dependence that sets in whereby the body stops manufacturing it as much or becomes less responsive to it, so I wonder if the same thing wouldn’t happen if we had a chemical specifically designed to increase serotonin levels, i.e. the body senses that there is plenty of it already, only not in the right places, and stops producing it as much, so after awhile the patient is back to square one?
Just a WAG, but the problem may reside in the “blood-brain barrier”. Basically, that term reminds us that it is actually quite difficult to get things out of the bloodstream and into the brain (thank goodness - otherwise, our nervous systems would be exposed to every transient change in our blood chemistry from things like meals, etc.)
My point is that it may be much easier to make drugs such as SSRI’s which, evidently, cross the BBB, than it is to make direct serotonin agonist drugs that get across.
It also seems that giving a drug that causes the synthesis of extra serotonin would have a higher possibility for toxic effects on overdose. On the other hand, by relying on natural serotonin levels, toxic levels of serotonin would be more difficult to achieve.
I read somewhere (maybe on the dancesafe’s “neuropharmacology of Ecstasy” slideshow?) that, because serotonin itself won’t pass through the blood-brain barrier, you can’t directly supplement it, and the serotonin precursors like 5-HTP don’t increase serotonin levels very much. Whereas SSRIs, by plugging the reuptake mechanism, effectively increase the levels of serotonin by quite a bit.
In other words, you can increase serotonin levels with supplements like 5-HTP, but not by very much. But SSRIs increase the levels significantly.
(I could be wrong about that, though – I’m too lazy to go find it again.)
Analogy wise this is what Ive read. Not exactly my area of knowledge though.
Think of it as a pipe being too small, with the serotonin being what needs to go through the pipe to help the brain. Increasing the amount of available serotonin wont do anything to fix the rate at which the serotonin goes through the pipe, so it doesnt really help much.
So the real answer is to increase the diameter of the pipe so more serotonin can flow through at one time, which is where the SSRI’s come in.
Otara
Increasing the amount of serotonin runs a higher risk of inducing mania. My understanding is most people have the correct level of serotonin, it is just the reuptake prevents normal transfer.
Or you could put the plug in the sink or bathtub or whatever – that would let your trickle of serotonin fill it up eventually. Which is basically what SSRIs do: they fit onto the receptors that sweep up serotonin from the synapse, so instead of pulling serotonin out of the synapse (where it’s actually going to be used) and back into the cell, they just let the serotonin accumulate in the synapse.
It’s not a perfect analogy, but it’s okay.
Wiki says:
So it looks like adding more serotonin is counterproductive after a point. However, there are both activities and foods that can help people raise their serotonin levels naturally. Dr. Daniel Amen has written about these effects in some of his books and John Gray picked up some of that information and used it in his Mars And Venus Diet and Exercise Solution. This is why some folks with lesser degrees of depression can help themselves through exercise and diet change (though many will still need meds).