Why are SSRI’s too stimulating !!!!!!

[AntsyVee]

As per above, there is no way of knowing how an AD will work other than trying it, John. Sorry, but no amount of poring through med data will find you *the* AD. You might as well pick one out of a hat.

^^^Very true. I think it's like this for most drugs for about any condition. I know I've had to experiment with different kinds/combos for my allergy meds. I had to do it with birth control. My buddy had to do it with their asthma meds. Another friend had to do it with diabetes pumps vs. injection vs. pills. It's just the way it works. Just think, the sooner you get starter, the faster you're on your way to figuring it out.

[SideFX]

^^^Very true. I think it's like this for most drugs for about any condition. I know I've had to experiment with different kinds/combos for my allergy meds. I had to do it with birth control. My buddy had to do it with their asthma meds. Another friend had to do it with diabetes pumps vs. injection vs. pills. It's just the way it works. Just think, the sooner you get starter, the faster you're on your way to figuring it out.

Thanks PDU I’ve got a week or so to pitch my tent in one camp and as you say, until I try something different nothing is gonna change and I’m just gonna continue scrapping along, missing out on my life. Pandemic put to one side...I have said that if I got Covid and if finished me of, that would be fine by me and that’s just not normal.

I do get relief now in the evening and feel much more hopeful and stable, but never full remission and I’ve settled for not second but third or fourth best ie the best of the worst.

Do you think that the Pregabalin might be causing depression and anxiety, as it’s not a very nice drug and half life is an issue. I keep thinking yeah I’ve got it straight in my head, then think no I haven’t - I’m scared of the consequences of switching meds it really is a huge fear right now.

What do I do if it all goes south and I could lose everything I’ve pushed through and worked to put my life back together !!!!! It’s a truly scary thought and I imagine the worst case scenario I can’t help it pal. So it’s amatryptiline or come of pregabs????? Your thoughts on the pregab as it gives me many SideFX too thank you John

[panic_down_under]

I have said that if I got Covid and if finished me of, that would be fine by me and that’s just not normal.

No, it isn't. A permanent 'solution' to a temporary problem never is, John.

Do you think that the Pregabalin might be causing depression and anxiety, as it’s not a very nice drug and half life is an issue.

Not directly, but if it is causing problems then that can get people down.

What do I do if it all goes south and I could lose everything I’ve pushed through and worked to put my life back together !!!!!

This may not be an either/or decision, John. How long before your situation improves enough to be able to risk changing meds without losing everything should it go pear shaped and can you keep going the ways things are atm until then? You need to make your situation clear to your psychiatrist so that it is taken into consideration in formulating the plan of action.

So it’s amatryptiline or come of pregabs????? Your thoughts on the pregab as it gives me many SideFX too

If you came off pregabalin first where would that leave you? The entire combination of meds you're on aren't working that well and taking one out of the mix is unlikely to improve things, imo, but it could make things worse. Replacing the ineffective AD with one that may work with fewer side-effects is more likely to help.

[SideFX]

No, it isn't. A permanent 'solution' to a temporary problem never is, John.



Not directly, but if it is causing problems then that can get people down.



This may not be an either/or decision, John. How long before your situation improves enough to be able to risk changing meds without losing everything should it go pear shaped and can you keep going the ways things are atm until then? You need to make your situation clear to your psychiatrist so that it is taken into consideration in formulating the plan of action.



If you came off pregabalin first where would that leave you? The entire combination of meds you're on aren't working that well and taking one out of the mix is unlikely to improve things, imo, but it could make things worse. Replacing the ineffective AD with one that may work with fewer side-effects is more likely to help.

Sorry for the late response PDU thanks as usual for very wise words and I have thought that Pregabalin would stop me falling asleep - gaining weight - water in ears and head sensation....But could make other SideFX much worse.

It all scares the shit out of me right now and has done for years. I just don’t want to go the same way as my parents and feel that a bad decision could lead to that !!!! Like you say I will speak with my Pdoc who thinks reducing Mirtazipine is the way to go, but I don’t see the benefit - So I’ll throw the ball firmly in his court and see what he comes up with.

Thank you and I will post back after I see him on the 16th if that’s okay Ta John

[SideFX]

Sorry for the late response PDU thanks as usual for very wise words and I have thought that Pregabalin would stop me falling asleep - gaining weight - water in ears and head sensation....But could make other SideFX much worse.

It all scares the shit out of me right now and has done for years. I just don’t want to go the same way as my parents and feel that a bad decision could lead to that !!!! Like you say I will speak with my Pdoc who thinks reducing Mirtazipine is the way to go, but I don’t see the benefit - So I’ll throw the ball firmly in his court and see what he comes up with.

Thank you and I will post back after I see him on the 16th if that’s okay Ta John

BTW PDU What role does increasing Norepinephrine play in anxiety and panic disorder - Surely this would increase anxiety??? Ta John

[panic_down_under]

I have thought that Pregabalin would stop me falling asleep - gaining weight - water in ears and head sensation....But could make other SideFX much worse.

Pregabalin has a similar effect on the brain as BZDs, just by a different route, John. BZDs slow neuron 'firing' by helping to increase the influx of negatively charged chlorine ions which makes it harder for the cell to raise its typical resting voltage from -70 mv to the depolarisation (firing) voltage of -55 mV, pregabalin inhibits the influx of positively charged calcium ions instead. Sedation is a common side-effect.

What role does increasing Norepinephrine play in anxiety and panic disorder - Surely this would increase anxiety??

It might if noradrenaline/norepinephrine (NA) reuptake inhibitors increased NA levels - and they do for a few weeks at the beginning, but just as with serotonergic ADs and serotonin levels, with chronic dosing they actually reduce NA synthesis and expression. OTOH, anxiety and/or depression increase NA and serotonin (also dopamine) levels significantly. These disorders are not caused by too little of this, or that neurotransmitter, just the opposite. See: Zangen A, 1999 and my Serotonin - The 'chemical imbalance' myth.

[pulisa]

It's probably a stupid question but what does your psychiatrist say about referring you for trauma therapy? Meds don't appear to be doing much for you long term yet you have the legacy of what happened to your parents hanging over you and haunting you permanently..Medication change will add to that awful fear as you say..

[SideFX]

Maybe the improvement was due to remission, not the venlafaxine, John. Anxiety disorders and depression wax and wane over time. If an AD at maximum dose isn't working within 12 weeks or so, maybe an extra couple of weeks if it isn't the first time on ADs, or is fluoxetine, then it is unlikely to at 6/9/12 months.

Why did you keep taking mirtazapine and venlafaxine for so long if it wasn't working?



ADs usually kick-in at 4-12 weeks the first time with the top of the bell curve at 6 weeks.



The dual action of most of them, plus the combination of receptors they hit.



It is a more potent NET inhibitor than the other SSRIs but much less so that many of the TCAs.



You might have done just as well on another SSRI.

Hi PDU I know it’s been a long time and I would like to seek your advise again…In the end I remained on all 4 meds and over the past few years, got back to about 60/70% ability to cope with life.

However I have very slowly been tapering off the Pregabalin and got from 600mg to 150mg. Then I got slammed with huge withdrawals, or at least I am putting it down to the cumulative drop.

Anyway it’s been 5 weeks and although I feel a bit better, I’m still in distress and trying to continue working. Thing is I have the shakes, hot flashes, burning skin sensations back. Panic and anxiety, mixed with some depression. I fear the end is coming and I’m afraid and don’t know what to do. Could you kindly revisit this thread and give some valuable input, as I was never in remission after 6 long years. But able to get by, without everything being a white knuckle ride.

I am still on Vortioxitine, Mirtazapine, Diazepam and now up dosed to 300mg Pregabalin

My GP doesn’t know what to do and has advised that it could take some time to stabilise back to where I was 5 weeks ago. Not healed, but able to cope with life.

Can we have a discussion around meds please as I know you are a fountain of knowledge. Thanking you in advance John

[panic_down_under]

However I have very slowly been tapering off the Pregabalin and got from 600mg to 150mg. Then I got slammed with huge withdrawals, or at least I am putting it down to the cumulative drop.

...Thing is I have the shakes, hot flashes, burning skin sensations back. Panic and anxiety, mixed with some depression.

How long after the last dose decrease did you begin having these symptoms, John?

I am still on Vortioxitine, Mirtazapine, Diazepam and now up dosed to 300mg Pregabalin

My GP doesn't know what to do

Did he start you on all these meds, or a psychiatrist?

Imo, there are two significant issues with your med regime. Firstly there's now good evidence¹ that benzodiazepines both worsen anxiety in the longer run and reduce the effectiveness of serotonergic ADs. The second is that the diazepam and pregabalin are basically doling the same job, slow the 'firing' rate of neurons, albeit from different directions. Diazepam does it by increasing the inflow of negatively charged chlorine ions which makes it harder for a cell to raise its electrical voltage to the depolarization level. Pregabalin slows firing by decreasing the influx of positively charged calcium ions. I don't see the point of taking two meds to do the same thing. It would have been more efficient to just raise the dose of one of them.

Which brings us to the other two. Despite what is says on the packaging, mirtazapine isn't a true AD, but a sedative so its main role in your case may be to help you sleep and it may reduce anxiety to some extent through sedation.

Vortioxetine combines the actions of a SSRI with that of buspirone (Buspar). It was noticed that buspirone can enhance the effectiveness of SSRIs and other serotonergic ADs and also ease some of their side-effects. So some bright spark decided to make an AD that had the attributes of both in a single pill. While the idea might be good on paper, vortioxetine hasn't exactly set the AD market on fire. I suspect the reason is the AD has a fixed ratio of the combined attributes whereas when adding buspirone to a SSRI there is are a wide range of possible ratios for fine tuning.

Which raises the question of is it worth continuing with vortioxetine, or would another AD be better? I don't know. It comes down to whether vortioxetine is not effective, or is it being inhibited by the diazepam?

I think taking the diazepam is more problematic than the pregabalin, but you really need to be talking with a psychiatrist about this, imo.

[1]
Boldrini M, Butt TH, Santiago AN, et al. (2014)
Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract | Full text)

Sun Y, Evans J, Russell B, et al (2013)
A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.
Neuropharmacology. Sep;72:20-8 (Abstract)

Song J, Zhong C, Bonaguidi MA, et al (2012)
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
Nature. Sep 6;489(7414):150-4 (Article | Study full text)

Wu X, Castren E. (2009)
Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells.
Biol Psychiatry. Jul 1;66(1):5-8 (Abstract)

See also: the 'Ugly' part of Benzodiazepines: The Good, The Bad, and the Ugly.

[SideFX]

[QUOTE=panic_down_under;2073634]How long after the last dose decrease did you begin having these symptoms, John?



Did he start you on all these meds, or a psychiatrist?
A psychiatrist did in whilst in hospital

Imo, there are two significant issues with your med regime. Firstly there's now good evidence¹ that benzodiazepines both worsen anxiety in the longer run and reduce the effectiveness of serotonergic ADs. The second is that the diazepam and pregabalin are basically doling the same job, slow the 'firing' rate of neurons, albeit from different directions. Diazepam does it by increasing the inflow of negatively charged chlorine ions which makes it harder for a cell to raise its electrical voltage to the depolarization level. Pregabalin slows firing by decreasing the influx of positively charged calcium ions. I don't see the point of taking two meds to do the same thing. It would have been more efficient to just raise the dose of one of them.
Pregabalin did far more and continued without tolerance, the benzo did nothing after a few weeks, as is usual for benzos.

Which brings us to the other two. Despite what is says on the packaging, mirtazapine isn't a true AD, but a sedative so its main role in your case may be to help you sleep and it may reduce anxiety to some extent through sedation.
I agree mirtazipine is a very weak AD, but a strong antihistamine, however in combo with venlafaxine years ago, was my saviour

Vortioxetine combines the actions of a SSRI with that of buspirone (Buspar). It was noticed that buspirone can enhance the effectiveness of SSRIs and other serotonergic ADs and also ease some of their side-effects. So some bright spark decided to make an AD that had the attributes of both in a single pill. While the idea might be good on paper, vortioxetine hasn't exactly set the AD market on fire. I suspect the reason is the AD has a fixed ratio of the combined attributes whereas when adding buspirone to a SSRI there is are a wide range of possible ratios for fine tuning.
Not up to speed with this AD, just know I struggled to tolerate it and may still do, don’t know anymore

Which raises the question of is it worth continuing with vortioxetine, or would another AD be better? I don't know. It comes down to whether vortioxetine is not effective, or is it being inhibited by the diazepam?
Diazepam had no effect on my previous recover in 2012 and I discontinued it easily

I think taking the diazepam is more problematic than the pregabalin, but you really need to be talking with a psychiatrist about this, imo.
Okay thanks for your input anyway Ta John