Advice very much appreciated

Jaxx wrote:Thanks ill look into that.
Any ideas on the combo Nortriptyline + Trintellix that is often mentioned at boards?

That combo would yield too much serotonin buildup. So no, not a good idea imHo. "California Rocket Fuel" which is Mirtazapine + Effexor is something that has sort of that premise behind it, but its far different as the former is primarily a serotonin antagonist, while Effexor is a stimulant norepinephrine-serotonin reuptake inhibitor. The combo yields norepinephrine activation because of the combined effects on norepinephrine systems compliment each other.

Nortriptylline + Trintellix would be all serotonin enhancement, even though Vortioxetine has serotonin antagonism, it still also has SERT-inhibiting properties, so on its own it is one thing, but with other SSRI's it is going to largely 'pro-serotonin'.

Therefore, Vortioxetine and Nortriptylline are a bad combo.

That is great feedback, although im a bit surprised. Nortriptyline is rather weak on serotinine (at least ive been told), but it is significantly stronger than Mirtazapine then? My experience with mirtazapine is somewhat different than nortiptyline as well; sedating versus activating for me.

Jaxx wrote:That is great feedback, although im a bit surprised. Nortriptyline is rather weak on serotinine (at least ive been told), but it is significantly stronger than Mirtazapine then? My experience with mirtazapine is somewhat different than nortiptyline as well; sedating versus activating for me.

If you look at the table you'll see Nortriptylline affinity for Serotonin Transporter is very close to its NET (norepinephrine transporter) affinity.
https://en.wikipedia.org/wiki/Nortriptyline#Pharmacology

Mirtazapine is an alpha-2-antagonist, and serotonin antagonist mainly, is thereby increases noradrenaline action in neurons, the sedating effect is due to its antihistamine action, however, is more apparent at LOW (15-30 mg) doses, while high doses (45 - 60 mg) of mirtazapine tend to be more stimulating.

It is my experience that all drugs that act on norepinephrine tend to have a 'sensitization' effect initially, meaning you get a buzz first on it, but then that effect dwindles, but the other benefits usually remain. I'd say all for all, norepinephrine-reuptake inhibitors and stuff like nortriptylline/amitryptilline are far more 'stimulating' than mirtazapine and like drugs, but it is specific to the person. Some people get ZERO energy boost from tricyclics, and others feel almost manic on them.

That indeed makes sense. Think the basic idea of the combo was to combine 5ht1a agonist properties with potent 5ht2a & c antagonist properties.

Small update, been 3 weeks on Nortriptylene now, and i feel it still hasnt "set". Like an SSRI if gives a numb (fysical) feeling, and a somewhat relaxing feeling. Side effects are mainly dry mouth and a somewhat faster heart beat and a little elevated blood pressure.
Only serious side effect is genital numbness, less than on paxil, but still very much unwanted. Still a feeling that everything is a bit off, although i experience more relaxation than before... Was hoping for more activation, but this isnt unpleasant...

Any experience with Buspar augmentation? Saw numerious of possitive reports, but that was almost always with an SSRI. I dont want to stop this too soon, i actually feel it helps a bit with PSSD, as libido is somewhat up.

Jaxx wrote:Small update, been 3 weeks on Nortriptylene now, and i feel it still hasnt "set". Like an SSRI if gives a numb (fysical)  feeling, and a somewhat relaxing feeling. Side effects are mainly dry mouth and a somewhat faster heart beat and a little elevated blood pressure.
Only serious side effect is genital numbness, less than on paxil, but still very much unwanted. Still a feeling that everything is a bit off, although i experience more relaxation than before... Was hoping for more activation, but this isnt unpleasant...

Any experience with Buspar augmentation? Saw numerious of possitive reports, but that was almost always with an SSRI. I dont want to stop this too soon, i actually feel it helps a bit with PSSD, as libido is somewhat up.

Those are all 'typical' experiences/side-effects for SSRI's, minus the elevated heart rate & blood pressure which are coming from the norepinephrine-enhancing activity of nortryptiline. You could try adding Buspar @5 mg twice per day to start, possibly moving up to 15 mg x3/day, it might help level out your heart rate and produce a calmer feeling, at the same time, buspirone's alpha-2-antagonism [!] may produce additional stimulation to the noritryptilline, so it might help, might also make things worse - depends on how your body reacts...I'd be careful of high-doses, start low - if you are gonna' do it.

So far my energy levels are up significantly, which is nice. Been a couple of years that i had to do stuff because i would get restless otherwise.
I still feel numb and have little emotions though. Ive read that abilify acts as a dopamine regulator. Is this something to conside?

Jaxx wrote:So far my energy levels are up significantly, which is nice. Been a couple of years that i had to do stuff because i would get restless otherwise.
I still feel numb and have little emotions though. Ive read that abilify acts as a dopamine regulator. Is this something to conside?

Abilify is not a good option, it will really make you ''restless''. If anything, I would consider a dopamine reuptake inhibitor like Amineptine, or possibly Catuaba + Flowering Quince extract. The medication Selegiline still seems a good suit, but if it isn't an option try the above.

So no, I wouldn't consider Abilify at all, its safer in terms of endocrine profile and hormones than other drugs in its class, and generally is a safe drug, but the neuromuscular side-effects are simply unbearable for most people.

The thing is, no matter which medication you try, especially if it falls into the 'typical' class of medications and commonly prescribed ones, there will be noticeable side-effects, with very few exceptions.

Yeah i indeed read that alot of people get restless from that stuff. Remarkable that some get it to help with their restlessnes. Anyway, this goes off my short list for now, especially for this combo.
So far nortriptyline isnt too bad, better than paxil (after 6 weeks that is).

Jaxx wrote:Yeah i indeed read that alot of people get restless from that stuff. Remarkable that some get it to help with their restlessnes. Anyway, this goes off my short list for now, especially for this combo.
So far nortriptyline isnt too bad, better than paxil (after 6 weeks that is).

The good thing about nortriptyline is it is less messy than Amitryptiline, because there is less conversion needed, and less metabolites being produced, therefore, the effects are a little 'cleaner' and more straightforward.

Im on buspirone for a week now, and so-far it has been very positive. I have more energy and especially in the morning i wake up more rested. Feel a little restless, but it's not too bad. No real effects on libido, but erections seem far better.

One thing im noticing, and have seen at other boards as well, is a slight continious pressure on the throat (thyroid?). I had these in the past as well a bit, especially the first weeks on wellbutrin and moclobemide. Do you know what this could be? They were often a first sign of a postive window, where i almost felt healed, but they only lasted a week or so.

Jaxx wrote:Im on buspirone for a week now, and so-far it has been very positive. I have more energy and especially in the morning i wake up more rested. Feel a little restless, but it's not too bad. No real effects on libido, but erections seem far better.

One thing im noticing, and have seen at other boards as well, is a slight continious pressure on the throat (thyroid?). I had these in the past as well a bit, especially the first weeks on wellbutrin and moclobemide. Do you know what this could be? They were often a first sign of a postive window, where i almost felt healed, but they only lasted a week or so.

Very glad to hear! Yeah Buspirone is hit or miss, some folks get lots of benefits on it, some receive no benefit at all - I am glad you are one of the responders, keep your spirits up, and enjoy life!

Thanks!
It's a significant change, also on my feelings. I would say anhedonia is almost completely gone and i definately experience more emotions.
Actually, I also re-experience the downsides of being super sensitive to sounds and my environment again, one of the reasons i went to SSRI's in the first place.
No impact on libido, but i think it's wise to wait-and-see for now. Might taper off the nortriptyline completely in a couple of weeks, think it's the buspar that is working, not so much the combination.

Jaxx wrote:Thanks!
It's a significant change, also on my feelings. I would say anhedonia is almost completely gone and i definately experience more emotions.
Actually, I also  re-experience the downsides of being super sensitive to sounds and my environment again, one of the reasons i went to SSRI's in the first place.
No impact on libido, but i think it's wise to wait-and-see for now. Might taper off the nortriptyline completely in a couple of weeks, think it's the buspar that is working, not so much the combination.

I would agree its the combination, Buspirone is an alpha-2-antagonist via its metabolite 1-PP (1-(2-Pyrimidinyl)piperazine); that means it increases noradrenaline, including in humans, which is consistent with these studies [1] [2][3]. Nortryptiline is a norepinephrine-reuptake inhibitor, so the combination of Buspar and Noritryptilline probably boosts energy by doubling norepinephrine levels.

Due to the continious high blood pressure, myself and my doc decided to see what would happen if i'd quit the nortriptyline and continued the buspirone.
Im almost tapered off the nortryptiline completely (after 3 weeks), but so-far the results are not great.
It was the first time i got sick while tapering off any antidepressant(incl. paxil, fluvoxamine,escitalopram, mirtazapine etc), which caught me by surprise. Although it might be a bit too early to draw conclusions looking at the medication's half life, my anhedonia seems to be back and even my morning wood is gone...

Do you see an alternative for the nortriptyline to try? It's was the first time i experience high(er) bloodpressure, although i didnt really measure it much on Wellbutrin.

My doc is a fan of tranylcypromine, not sure i want to go that route, especially i still believe its PSSD, not depression.

Im a bit puzzled how my body reacts atm. Wellbutrin was horrible (2 years ago, my anhedonia was less at the time though) but nortirptyline&buspar got a different reaction.

Any thoughts?

Jaxx, Nortryptiline has a higher Norepinephrine-Reuptake-Inhibiting action than Bupropion. That's probably Why. Wellbutrin actually has more ''releasing'' action than Uptake-inhibiting action. You could try an MAO inhibitor, might have equivalent results.

I dont completely understand the releasing comment.

Wellbutrin was quite strong when i took it, too strong, but its impact on noradrenaline and dopamine inhibibition should be lower than the northryiptyline+buspar combination, or am i missing something?

Do you have any personal experience with MAOI''s? (not Aurorix)

Wellbutrin and Nortryptilline act differently, Jaxx. Wellbutrin increases the norepinephrine 'flow'...the amount of firing. Nortryptilline preserves more Norepinephrine and prevents it from leaving Brain.

No, no experience except with Moclobemide which boosts Energy much & Syrian Rue which boosts Mood and can increase Euphoria to other substances.

Make sense now?

Ah i was indeed not aware of that difference, thanks for the elaboration!
This has been a longer search than i anticipated, but i guess thats not uncommen.

Jaxx, anything new?

Hi!

I had to stop nortriptyline due to the elevated hearth rate and blood pressure and the positive effects of buspirone decreased over time, so i've taped that off too. Looking back it mainly had a positive effect on erection quality and some general energy.

I have been experimenting with a low dose of paxil (1 mg) which gave me great relief of the anhedonia.
I actually feel a bit like my old self again, without the libido sadly, but for now i accept this progress. I also feel a bit nervous again from time to time, which was rare for me for over 2 years. Ive read in some reported cures that libido is that least to come back, so ill be a bit more patient.

It all makes me think if this isnt a hormonal issue. For instance this study talks about the impact of low dose SSRI on estrogen levels
https://www.theguardian.com/science/2010/sep/17/low-dose-prozac-pms.

On the PSSD forum they are discussion a (possible) remission with estradiol.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854098/#!po=21.4286

Any insights you have on this theory? I might push for an extensive hormone test soon, to see if something comes up.

I'm not sure why you would find going back on an SSRI is a good idea, but IMO you are working backwards.

Might feel some relief now, but Anhedonia coming back harder later on isn't worth it.

As far as Estrogen, I agree that SSRI's affect aromatase and Estrogen, but its reckless to potentially worsen your own overall health by adding a unspecified amount of pure Hormone to your body.
Read this article --> https://area1255.blogspot.com/2016/05/insights-into-pssd-article-part-2.html?m=1

Ow i definately agree on the second point, i would only consider any type of hormone treatment by professional supervision. Still an interesting field to look into imho.

About the SSRI; as far as i know, 1mg is 1/20th of the therapeutical dose for paxil, and should not raise serotonine (significantly).
Im not sure why this seems to work, but for now im staying on a very lose dose, either 1 time a day, or any other day.
Interestingly, other people that have tried it report morning wood improvements, which i can confirm.

And i understand your doubts about involving SSRI as a relief/solution. I am not saying this is the holy grail, and i'm open for suggestions, but for now its a relative safe way that seems to help somehow.

Jaxx wrote:Ow i definately agree on the second point, i would only consider any type of hormone treatment by professional supervision. Still an interesting field to look into imho.

About the SSRI; as far as i know, 1mg is 1/20th of the therapeutical dose for paxil, and should not raise serotonine (significantly).
Im not sure why this seems to work, but for now im staying on a very lose dose, either 1 time a day, or any other day.
Interestingly, other people that have tried it report morning wood improvements, which i can confirm.

And i understand your doubts about involving SSRI as a relief/solution. I am not saying this is the holy grail, and i'm open for suggestions, but for now its a relative safe way that seems to help somehow.

Well if it helps you then go for it, another idea is to combine it with a serotonin antagonist like Metergoline.

Idea Labs sells it.

http://www.idealabsdc.com/lab/

I might look into that, although i always thought it would be most useful for people with serotonine like side-effects, like genital numbness.

Another thing, how would you see the PSSD simularities with propecia issues?
There was this nice article, that also shows that blood plasma hormone levels dont exactly match what is measured in CSF.

https://www.ncbi.nlm.nih.gov/pubmed/28408350