Why do most anti depressants take 4 to 6 weeks to take effect.

[ricardo]

I know for short term relief drugs like Valium and Xanax and Ativan act very quickly but are recommended only for short term use but why do the modern drugs such as the numerous choice of SSRI'S nearly always take a good few weeks to start to kick in and invariably one feels worse when one starts taking them.

One would have thought in 2015 where statistics show that anxiety related and depression illnesses are on the rise annually, that we haven't got the technology to improve the drugs currently available.

I am not advocating that these drugs are a cure but in many cases can improve the quality of life for an individual.

[Sunflower2]

I can only give my own experience but I'm taking sertraline, having had a massive phobia of it for years and was certain it would not work and I would feel so sick I wouldn't be able to stick with it.

I felt sick once (most likely due to anxiety) and after 4 days the feeling of a cloud of dread lifted. I didn't expect to feel anything and hate the fact I'm taking medication as I always wanted to do it alone. I've now taken it for 3 weeks and I've achieved things I never thought I'd be able to face and haven't faced since developing severe anxiety and panic attacks 2 years ago.

I know everyone is different and maybe I was just lucky but it's helped so much in such a short period of time. You just have to read through my history to know how I couldn't even imagine taking any medication at all! I took the contraceptive pill for 3 days before giving up due to anxiety about it!

[yenool]

My guess is because the chemical changes they cause have some kind of affect on the brain which causes it to be remolded slightly and this takes time.

I certainly don't buy the 'chemical imbalance' theory because if these pills really were correcting an imbalance you would expect to see improvement almost right away. Like when taking a thyroid hormone or something.

It is also important to factor in that a lot of people with 'depression' are actually suffering from understandable situational low mood and would have got better in the 2-3 month time frame anyway..... usually once the bad event or life stress has passed.

[MyNameIsTerry]

I certainly don't buy the 'chemical imbalance' theory because if these pills really were correcting an imbalance you would expect to see improvement almost right away. Like when taking a thyroid hormone or something.

It is also important to factor in that a lot of people with 'depression' are actually suffering from understandable situational low mood and would have got better in the 2-3 month time frame anyway..... usually once the bad event or life stress has passed.

Exactly. I thought they had stated that whilst low Serotonin had been noted in people with depression, the was no proveable link as they are still unaware whether that causes depression or whether it is an outcome of depression.

Its also folly to just prevent loss. Why not look at diet too and make sure it is sufficient to even create enough Serotonin? GP's don't seem to bother with that and it could easily be argued based on your last statement that increased demand for neurotransmitters are not being fulfilled in times of stress as they aren't with many other nutrients.

[MrAndy]

recent studies show most ADs make changes in the brain within 3 hours,no idea why it takes 3-4 weeks to kick in but maybe thats because we have to get used to the change ?

[pulisa]

I suspect that in 10 years time the drugs being prescribed now will be obsolete. It does seem farcical that this kick-in period has to be endured by people desperate to get some respite from their symptoms.

[MyNameIsTerry]

I've used an example a few times to demonstrate a comparison to physical health:

You go to A&E with a broken nose, the doctor examines you and you ask if he can help. The doctor replies "Yes, of course, but first let me punch you on the nose".

Thats like a GP dishing out SSRI/SNRI's!

NoPoet's thread shows examples of some of the newer meds coming out or in the pipeline:

http://www.nomorepanic.co.uk/showthread.php?t=54701

The introduction of Glutamate based meds is interesting given it influences both excitory & inhibitory neurotransmitters. The precursors of Glutamate are very easy to purchase and very cheap as well as being available in many supermarkets. I would prefer to see TMS come through though, especially since we have some similiar devices on the market for purchase now.

[Richard1960]

Anti Depressants may get to the brain quickly but the rest of your body needs to tolerate them too which takes time,also its not yet quite understood about the serotonin link lots of research i have done proves contradictory depending who is writing it.

If it is the case it has to work on chemicals in the brain also and build them up that would take time and produce side effects.

On another point it would be a good idea if we could have perhaps dieticians trained up to take a look at people diets and se if a change to certain foods would help,certainly might be cheaper then other methods but worth a try.

[MrAndy]

ssris are like playing darts in the dark with your head

[MyNameIsTerry]

ssris are like playing darts in the dark with your head

...and I'm no Bobby George!!! :doh:

[Pipkin]

I'm no medic but it has to relate to your body adjusting to higher levels of neurotransmitters and also the gradual build up of the drug in your plasma levels.

I found that my meds didn't take full effect for around 3 months but they really work for me. As others have said though, on their own they're not enough. My advice is always to get out of the house (or at least get out of bed) and start a healthy routine. Force yourself to do things your anxiety is stopping you from doing. It's painful and temporarily increases anxiety but the longer-term effects are worth it.

Start some online CBT if you think that might help but take it seriously and practise. Meet some friends and talk things through. If that's not possible, share some of your experiences here but do it at set times and don't let your life revolve around internet communication. This site has helped me tremendously but it's important to be active, both physically and mentally.

Finally, and this is where there is often disagreement, force yourself to work. Start small if you're not currently in work and build up. The interaction with others and the support of good colleagues in the right environment can be life changing. If you've had bad work experiences before, don't let them deter you. Some volunteer work can also be very rewarding, especially as a first step. They are usually very understanding of the problems we face. This is all incredibly difficult, I know, but the rewards are well worth it.

And if you are on meds and they are working (be it physiologically or just a placebo effect (who knows? It's likely to be a bit of both if I had to guess), stick with them. Don't be rushed to discontinue but never pin your hopes on drugs solving everything. I find they give me despite to do all the other things I've described.

May just be me, but that approach works well. Oh, and did I mention getting 2 dogs which keep me incredibly busy, demand activity and offer companionship when I need it? Priceless!

Take care

Pip

[MyNameIsTerry]

The plasma levels issue is in relation to "steady-state" which is 4-5 half lives of any drug. It looks like this:

Day....%
1........50
2........75
3........87.5
4........93.75
5........96.875
6........98.4735
7........99.25

Clear elimination has the following:

Day....%
0.........100
1.........50
2.........25
3.........12.50
4.........6.25
5.........3.13

When its under 5% its no longer clinically significant. It's more complicated than this when you consider how people taper as it will mean some overlap and then with some meds (e.g. Benzo's) you also have the storage outside of blood plasma which also needs elimination.

But as MrAndy says, there is clinical evidence that a drug is acting very quickly even if clinical effect doesn't appear evident.

But doesn't that make sense since you really don't want to wait 3 days for your Diazepam to kick in? By Day 3 it is considered clinically significant.

So, if you take an example like Citalopram which has a half life of 35 hours you are talking 105 hours before it becomes clinically significant and 175 hours before it can be at steady-state. If you look at Sertraline you get 26 hours for half life, 78 hours for clinically significant and 130 hours for steady-state. I think we should be keeping this in mind when we are increasing dosages so that we allow this to take place before pushing on as it could mess us up further but I often see GP's telling people to increase faster than this which shows they aren't very clear on this basic pharmacokinetic calculation or don't see it as relevant. But why risk it for a day or so?

This type of calculation is a guideline as well since there is no real way to calculate it from what I have read because it differs per person because it is influenced by liver efficiency, weight, etc.

---------- Post added at 08:21 ---------- Previous post was at 08:02 ----------

I think this explains how SSRI's interact with us at the most basic level I have read:

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor#Mechanism_o f_action

In the brain, messages are passed between two nerve cells via a chemical synapse, a small gap between the cells. The (presynaptic) cell that sends the information releases neurotransmitters (including serotonin) into that gap. The neurotransmitters are then recognized by receptors on the surface of the recipient (postsynaptic) cell, which upon this stimulation, in turn, relays the signal. About 10% of the neurotransmitters are lost in this process; the other 90% are released from the receptors and taken up again by monoamine transporters into the sending (presynaptic) cell (a process called reuptake).

SSRIs inhibit the reuptake of serotonin. As a result, the serotonin stays in the synaptic gap longer than it normally would, and may repeatedly stimulate the receptors of the recipient cell. In the short run this leads to an increase in signalling across synapses in which serotonin serves as the primary neurotransmitter. On chronic dosing, the increased occupancy of pre-synaptic serotonin receptors signals the pre-synaptic neuron to synthesize and release less serotonin. Serotonin levels within the synapse drop, then rise again, ultimately leading to down-regulation of post-synaptic serotonin receptors.[105] Other, indirect effects may include increased norepinephrine output, increased neuronal cyclic AMP levels, and increased levels of regulatory factors such as BDNF and CREB.[106] Owing to the lack of a widely accepted comprehensive theory of the biology of mood disorders, there is no widely accepted theory of how these changes lead to the mood-elevating and anti-anxiety effects of SSRIs.

The medical sites can explain this to a far more complex level.

Over time they basically reduce the number of receptor sites that can take up the neurotransmitter but they also make change to how the whole synapse is working in this process which is a bit more complicated.

The interesting thing for me is that last statement of how there is no widely accepted theory of how they cause mood-elavating and anti-anxiety effects. This is an interesting article about one such theory:

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

The article theorises that once down regulation is in effect, changes are not made directly to mood but to systems that are "upstream" hence why it takes an amount of time to see such changes.

That makes more sense to me. It also talks about therapy and how that has similiar influences.

[MavisReilly]

As a newbie to meds, and to the forum, this thread is very helpful to me. :flowers:
Thanks.

[MrAndy]

http://www.dailymail.co.uk/health/article-2762039/Antidepressants-affect-brain-just-three-HOURS-not-weeks-previously-thought.html

[ricardo]

http://www.dailymail.co.uk/health/article-2762039/Antidepressants-affect-brain-just-three-HOURS-not-weeks-previously-thought.html

Interesting article Andy

but you would have thought that as this drug is readily available here that this revelation would have come to light sooner.

[yenool]

These type of articles blur the lines between the biological/chemical changes the drug creates (very quickly?) and the clinical changes in mood or anxiety (often slow or not at all).

I think in 100 years medicine will look back at horror on SSRIs and other modern psych drugs................ just like we look back with shock at some of the treatments used 50 years ago now.

[MrAndy]

I think ADs have their place but I also think GPs dish them out like sweets

[pulisa]

These type of articles blur the lines between the biological/chemical changes the drug creates (very quickly?) and the clinical changes in mood or anxiety (often slow or not at all).

I think in 100 years medicine will look back at horror on SSRIs and other modern psych drugs................ just like we look back with shock at some of the treatments used 50 years ago now.

Too true.

[MyNameIsTerry]

I think in 100 years medicine will look back at horror on SSRIs and other modern psych drugs................ just like we look back with shock at some of the treatments used 50 years ago now.

Completely agree. It will be like Bones McCoy calling our surgeons butchers in that Star Trek film.

My surgery was founded as family practice under patents of the current senior partner who must be heading over fifty now. The father didn't believe in treating people with steroids and would happily let you end up in A&E when I was a kid.

---------- Post added at 23:17 ---------- Previous post was at 23:16 ----------


Interesting article Andy

but you would have thought that as this drug is readily available here that this revelation would have come to light sooner.

There was a cited evidence of it in my link too and that was from 2009 so either this med hadn't been tested specifically or I'm not sure what the point of the study was.