Why do SSRI's take so long to work?

[Mojo61]

Why do these tablets take such a long time to help? What is the mechanism behind it all? I've been on them over 4.5 months now and I'm still not right. I'd just like to know roughly how long it will take before I'm back to normal and can start enjoying my life again.

[swgrl09]

Huh, 4.5 months is a while. Have you noticed any positive changes during that time?

[Mojo61]

Yes, but it is sooooo slow! I was on 10mg for 3 months and then increased to 20mg 7 weeks ago.

[swgrl09]

Ah, ok. So it may just be that you haven't reached *your* optimal dose yet. I don't know the chemistry/biology behind why it takes so long, but good for you for sticking with it and not giving up!!

[pollynewsome]

I wish i knew.. im doing loads better at the 30mg than i was at 20mg, so maybe its worth discussing the increase with your doctor.. i was definite in my mind that i was not going to go beyond 20mg but im so glad i have.. The doc would like me to go to 40mg but i am definitely staying the course at 30mg till at least the 6 week mark.. Hope things start to improve for you mojo its just not fair!! xx

[Debs21uk]

I bet the main man Terry will know, his knowledge is immense :)

[Mojo61]

I bet the main man Terry will know, his knowledge is immense :)

Well I didn't want to say, but.......... :winks::winks::winks:

[Debs21uk]

This is quite interesting as a theory:

http://bjp.rcpsych.org/content/195/2/102

[Mojo61]

I can't really understand that. I'm obviously thick lol

[Debs21uk]

Lol it's not the easiest, I think it's saying it takes a while to affect the way we see things, we have a tendency to see things negatively so the meds work by changing our perception making it positive. I don't think they know, it's all speculation.

[Shazamataz]

You may need to increase again Mojo or maybe it's not the right medication for you and time to try something else? So frustrating isn't it?

[MyNameIsTerry]

They work in two ways.

First they start increasing the volume of Serotonin "pushed" into the cleft (the space between the sending receptor and the receiving receptor) which means the receiving receptor has more to extract from that space to pass on for the process it is needed for. What is also going on is at the side where the sending receptor is "pushing" the Serotonin out into that space, it is also being stimulated to reabsorb it.

This is where the longer term effect of SSRI's come in - down regulation. At the most basic level, it reduces the number of receptors that reabsorb the Serotonin back out that space.

So, what you end up with it 2 effects, more Serotonin being "pushed" in so the receiving receptor has more to try to "siphon" off but then because the down regulation occurs to effectively "plug up" those reabsorbing receptors (think of lime scale in a shower head), it leaves more in there because it is being more slowly reabsorbed out of that space.

The first effect takes place very quickly as it comes from the active drug stimulating it. The down regulation takes longer because it's a physical change. This is where you get into a multitude of answers because there is no single agreement and each med differs. Accepted research has shown it takes 2 weeks, 3 weeks, 20 days, etc but without knowing which med, it's not much of a guide. This is why they review meds at 8 weeks and decide whether to adjust or switch because by then something should be happening.

Research also shows that it can start to be felt very quickly, as in the same week. Escitalopram is known to show this, that's one I do know is referenced. There is also research showing how faster response can predict overall greater response long term. There is also something called the "monoaminergic hypothesis of depression" which is the most accepted hypothesis for depression when it comes to this neurobiology end. That also states that to predict it to work, you should feel side effects first.

The trouble is, that's all about depression because the bulk of the research has always been for that.

What Debs provided is a really good article. I read that one a couple of years back when I was trying to understand this stuff and it really helped me (it did take more than one attempt :winks:). You will see in that one how it talks more about the hypothesis in terms of the effects of increased Serotonin on our emotional thinking, mood, bias, etc. This is where negative thinking comes in as the result should be that negative thinking is "influenced" to change - which is why therapy can be shown to achieve the same since you make the change yourself, with proper guidance, and that alters how your Serotogenic system is working.

Those types of changes take some time and can only be measured through rating scales performed at certain points to see if we are showing signs of our thinking changing.