Anyone ever take a pure NRI with a synergistic agent?

[JohnBoy2000]

I'm finding it incredibly difficult to strike the balance with this.

Initially I was on reboxetine but, that interacted with the synergist (Mianserin) - plus it wasn't potent enough.

Now I'm on Atomoxetine with Mianserin (like a remeron analogue, but no 5ht value).

If the dose goes too high, I get very high heartbeat, particularly at night time if I'm taking a higher dose of Mianserin (60 mg).

So I lowered Mianserin to the starter dose of 30 mg - and went higher with atomoxetine - and seemed to get effects of receptor saturation?
Fatigue a little - maybe that was just a drug side effect.


Basically - it's unlikely anyone has taken Atomoxetine with Mianserin - but perhaps some of you have tried it with Mirtazapine?

How did you find attaining the correct doses?

Not so high as too induce night time activation, but not so low as to be ineffective?

Any insights?

 

[JohnBoy2000]

There is a microdialysis study of this combination therapy - showing an increase of about 10x when the alpha blocker is used, versus the transporter blocker in mono-therapy.

My question at this point - shrinks seem to start off with administration of the reuptake inhibitor - BEFORE - the autoreceptor blocker.

i.e. they'll give effexor - and if not implemented to full efficacy, they'll give remeron in addition.

Why not the other way around??

Can anyone answer this?

 

[JohnBoy2000]

I ask cause - I had been taking the approach of high dose autoreceptor blocker, and then lower dose reuptake inhibitor.

This seemed quite effective the first few days - I felt powerful - but side effects came on quick, and I had to downregulate the reuptake inhibitor it avoid night time activation and diarrhea (paradoxical - this is a symptom with no meds, or when meds go too high?).

In Stahls book - the prescriber's guide - he specifically notes that atomoxetine should be used in monotherapy - last resort used in combination therapy.

Maybe this is a psychiatric safety protocol.

But perhaps it alludes to the reuptake inhibitor being the foremost consideration - ahead of the "combination agent" - the autoreceptor blocker??

 

[Cotcha Yankinov]

Johnnyboy, I'm worried that some day your experimenting will result in some serious tachycardia and a cardiac event. Be aware of that possibility, and probably have something on hand (beta blocker?) just in case tachycardia becomes an issue (just to take in the mean time before professional medical help arrives).

Reuptake inhibitors have certainly been around longer than a2 antagonists and that may explain some of provider's preference to try them first. There was a move away from MAOIs largely because of the risks and side effects, but reuptake inhibitors are still a mainstay because they do work for many people. I'm not familiar with meta analysis of efficacy of mirtazapine vs. SSRIs/SNRIs but I would imagine that there is a lot of individual variation there, some people who don't respond to SSRIs respond to mirtazapine, and then some people absolutely hate mirtazapine apparently. Same can be said of SSRIs of course.

This kind of gets back to the "Psychiatry is an art" thing, in the sense that psychiatrist's jobs are to match a person to a med. We may have raw data on rates of antidepressant efficacy, but there are many different subtypes of depression and similar illnesses.

A psychiatrist specializes not just in treating disorders but diagnosing disorders. Self diagnosis doesn't work out very well, we can't get much insight or perspective. Its kind of like Plato's cave. Some of these issues may also be more peripheral (e.g. thyroid/endocrine) issues rather than purely neuropsychiatric.

 

[JohnBoy2000]

Yeah I have some serious increase in heart rate issues from time to time, depending on the dose.
It certainly is a fine and difficult balance to strike.

Psychiatry has little insights or anything really to offer when it comes to this particular combination.
In terms of psychiatric diagnosis - I mean, I guess that works well for some; RD Laing, a Scottish shrink prominent in late 80's early 90's, worked more from a premise that, a psychiatrist would have great difficulty getting sufficient patient insight to really be completely accurate in diagnosis and/or treatment.

I certainly favor the latter opinion - but that's just me.
Or maybe it's just the shrinks I saw - public system - might get 5 minutes tops with a different shrink every time; I seriously question the practice I've personally had experience with.

That being said - in the sinusoidal graph that represents symptom amelioration in my case, with this combination - when it's been good, it's been great; beyond any other drug or drug combination I've thus far had.
Then it peaks excessively, or troughs - thus my current dilemma.


In any case, whether it's the half life of atomoxetine - wearing off too early - or excessive activation from it, I wish I knew but, easy to sleep - and early wakening has been a consistent issue.

Curiously, last night I wake at 3 am - said "fuck it - I'm awake. Might as well be fully awake", so dosed 20 mg atomoxetine.
Within one hour, I was relaxed enough again to sleep through to 8 am.

I was of course under the impression that atomoxetine would induce activation - as it normally does.
Taken during the day, it does give me energy.

That being the case - splitting a high dose, one half later in the day - with a small mianserin/anti-hisatmine at night to send me off: that's the next approach.

Hopefully eventually I'll answer my own question but - again - if anyone has experiences with atomoxetine that may be germaine, regards to dose, time of dosing - go right ahead and throw it out there.

 

[Cotcha Yankinov]

With regards to experiencing a different effect than expected when taken at 3am, reuptake inhibitors just decrease the clearance of transmitters already released under endogenous cell firing, and endogenous cell firing is going to be different depending upon day vs. night and from mood to mood. As an example, serotonin cell firing differs largely depending on circadian rhythm/sleep phase, and normally NRIs augment serotonin cell firing during the day.

CY

 

[JohnBoy2000]

I finally figured out a pretty critical part to this particular riddle.

Strattera is dosed, sometimes once a day for ADHD.

But for maintaining higher NA synaptic levels - it damn well must be dosed according to its half life - therefore, twice a day.

The morning dose - then drug depletion, then night time autoreceptor blocker - was precipitating all kinds of issues, most prominently - poor response.

Twice a day dosing, and things are coming right with the world again.


Highest tolerable dose Mianserin, 60 mg.

Then, I'm currently taking the highest licensed strattera dose - 120 mg a day, divided to 60 mg morning and afternoon, roughly 6.5 hours apart (2 hour absorption, 5 hour half life).

It's good - but I actually think I may need higher for each divided dose.


This is where it gets complicated.

It's not licensed for depression (and no shrink I've ever seen has ever said I present with the remotest characteristic of depression - so I can't think of anything else to call it but, "noradrenergic dysfunction").

Only for ADHD, and obviously the response criteria is going to be a lot different.

In clinical trials, I've read of it going up to 180 mgs per day - which would be two doses of 90 mg.

That might do it - though maybe even 100 would be better.


The other thing is - this is really going to burden my financial situation.

This shit is costly as a bottle of 40 year old scotch.


In regards to side effects - they seem to be largely negated with twice daily dosing also.
It would seem the high NA levels, then the huge dip, the increase again with night time mianserin - was causing issues.

When level are kept somewhat consistent - it seems to be just fine.

 

[JohnBoy2000]

Still tweaking dosing.

That 90% receptor occupancy is a hell of a balance to try and hit.

I seem to have acquired mild facial twitches - which is a bit of a pain, but not the worst side effect.

It feels like a tension prmes around facial muscles, and release with an involuntary twitch.

Hopefully it will pass.
I tend to notice it mainly when not active/doing something.