Why antidepressants make you feel worse initially

[Peachypips]

Hi all- I found this on a general thread and thought it might really help us out. All credits are to 'Schtopper'.


Join Date: Jan 2011
Posts: 10

How SSRIs work, and why you feel worse initially.
Hi,

I've been reading these forums for a while, and I've been taking SSRIs for the last 3 years (Cipralex). One of the concerns I've noticed most people have when starting an SSRI or increasing it's dose is how crap they feel to start with. This causes a great deal of stress for the person as they begin to wonder whats happening, is their disease just getting worse and worse, are these drugs doing absolutely nothing for them?? etc etc.

So having not seen a real explanation of exactly how an SSRI works I thought I'd make this post to hopefully show people exactly WHY you often feel so aweful to start with.


First to understand this we need to know a little bit about the brain and about how nerves work.

The brain is essential a big dense bundle of nerves, nerves as we know carry electrical signals around our brain and body. Nerves are made up of nerve cells (called neurons but that doesn't really matter).

The important part to remember here is that nerve cells do not touch each other, there is a small gap between each cell (called a synapse, again not important). This gap prevents the electrical signal from going from one cell to another. So how does the signal get from one cell to another?

This is where neurotransmitters come in, these are chemicals released by nerve cells that tell a neighbouring nerve cell to pass the signal along. A bit like pass the parcel, where the signal is the parcel and the neurotransmitters are the people passing it around (essentially anyway).

Serotonin is one such neurotransmitter.

So when an electrical signal reaches the end of a nerve cell that deals with serotonin that cell releases serotonin into the gap (synapse), serotonin then crosses the gap and interacts with the nearby nerve cell and tells it to pass the signal along.

Once the serotonin has done it's job parts of the nerve cell then reabsorb the serotonin from the gap so that no more signals are passed until the next one comes down the nerve (if it stayed in the gap it would invoke more signals and for longer).

SSRIs, (Selective Serotonin Reuptake Inhibitors) interfere with this reabsorbtion process and thus serotonin stays in the gap longer, which equates to more serotonin and more signals. This is good for people with low serotonin levels (us).


That's all very interesting I'm sure but why do I feel like crap??

Well here's the thing, along with the releasing serotonin, and reabsorbing it, nerve cells also have parts that detect an increase in serotonin level and tell the nerve cell to stop producing anymore serotonin until the level drops. These are called autoreceptors.

Autoreceptors are the reason you feel like shit, so when you feel like crap blame them.

As I've said taking an SSRI will increase the amount of serotonin in your brain, or more specifically increases the amount in the synapses between nerve cells. Unfortunately the autoreceptors of the nerve cell pick up on this increase and tell the nerve cell to stop producing serotonin.

The result of this is that when you first start taking an SSRI your serotonin levels DROP.

How do they go up again??


Eventually with continuous use of SSRIs the autoreceptors become desensitised, that is to say they've continually told the nerve cell to stop producing serotonin but yet serotonin is still there. In short they simply give up. They stop telling the nerve cell to stop producing serotonin and your serotonin levels start to increase.

This desensitisation takes time, it doesn't happen over night and it won't even begin to happen until the SSRI levels have stabilised (which we already know takes 5-7 days anyway).

This is why you feel so bad, it's why your mood drops and your anxiety increases (fueld by the fear of not knowing whats going on).


I hope this isn't too complicated but it really helps me to understand why I feel so bad when i increase dose or start taking them, so to summarise:

SSRIs cause your serotonin levels to drop when you first start taking them.

Your serotonin levels will not rise until the autoreceptors in your brain have stopped working (become desensitised).

This takes time. For some people it could be a couple of week, for others a month or more.

[panic_down_under]

Unfortunately, the 'low serotonin' hypothesis as the cause of anxiety and depression is one of those zombie 'facts' which just refuses to die despite have been dismissed almost as soon as it was proposed, often helped along by pharmaceutical companies and doctors using it as a convenient simple explanation for how antidepressants work.

One of the earliest indicators the hypothesis was flawed is the French antidepressant tianeptine (Stablon) which enhances the reuptake of serotonin from the synapses, i.e. it has the opposite effect to SSRIs (when tianeptine and an SSRI are taken together they cancel each other out), yet it is at least as effective and usually begins working faster. This is not the only evidence against the hypothesis.

[Peachypips]

But antidepressants do cause a drop in seratonin initially- so the above is accurate in the way it describes why you feel worse before you get better.