Would you mind outlining other medications you have tried with doses?
Hey JohnBoy. I've had depression since I was about 10 and I'm now 37. So there've been quite a few that may be relevant:
Citalopram
Escitalopram
Sertraline
Mirtazapine
Venlafaxine
Fluoxetine
Bupropion
Atomoxetine
Imipramine
Memantine
Co-Dergocrine
Tramadol
Methylphenidate
Methamphetamine
Amphetamine
Modafinil
Various nootropics
There would be others I've tried but I can't really remember off the top of my head, nor the doses. Most doses would just have been standard adult male doses (eg escitalopram 20mg).
Ritalin was the best, cleanest, purest sleep aid I've ever used, but I couldn't afford to keep using it that way (I have to buy from online pharmacies. In the UK, until 2008, ADHD did 'not exist' in adults, and I haven't made the effort to get an adult diagnosis since).
Meth and amphetamines were mostly used recreationally, but I've also purified and synthesised into tablets for normal adult ADHD treatment protocols. I didn't find either particularly effective for ADHD, and the situational temptation to use recreationally is sometimes too strong.
Memantine and co-dergocrine (ergoloid) were just me thinking outside the box a bit while playing around with nootropics for exam periods.
Modafinil has been effective for both depression and ADHD (well, somewhat), though occasionally it provokes a mild hypomania and I can never sleep on it, even low-dosed very early A.M. (so by day 2, I feel absolutely wrecked).
Obviously it's very paradoxical for a stimulant to incite lethargy but - there was reference in one neuropharm text that, with NE receptors become completely saturated, this can happen.
Again, I'm not an expert but - I would assume on some level that, there was no underlying issue with NE receptors so, flooding them with increased unnecessary NE incited fatigue.
I based my assumption partly on the way I understand α2 adrenergic agonists to work. I would tend to think that, in people with different neutrotransmitter signalling patterns (like ADHD), it's quite plausible that idiosyncratic densities or concentrations of α2 adrenoceptors in certain parts of the brain could potentially lead to acute paradoxical reactions from localised elevations of NE. I'm hoping that - over time - this may resolve itself.
MOC does to appear to interact with µ/δ-opioid receptors with roughly half the affinity of naloxone, though I don't know how relevant that might be to somnolence (probably not at all).
I would guess in my case, no underlying issue with 5HT receptors or neurotransmission so, it's unnecessary enhancement brought about a counter productive outcome.
So - as you can tell, it does appear to be quite subjective.
Assuming the normal distribution curve also applies to reactions to various drugs, I think we could inherently assume that, although the majority will react in the specified manner, we would nevertheless expect certain proportions of a standard population to react in contrary or exaggerated ways to various drugs or combinations thereof.
Moclobimide certainly wouldn't be first line, not with any doctor or organization in Europe anyways, unless you requested it specifically?
I did have to request moclobemide. I was looking for something with a gentle side-effect profile. My experience with typical SSRIs, mirtazapine etc hasn't been good. A drug which starts to work almost immediately, can be controlled easily due to a short half-life, has no extrapyramidal symptoms and is minimally affected by tyramine seemed worthy of a shot.
Have a look at this chart for receptor binding affinities RE: NE/5HT etc.
Moclobimide isn't listed as it's enzymatic based, from what I understand.
MOC interacts with 5-HT2 receptors slightly in the
rat cortex, but not at all with ɑ1 and ɑ2. So it seems quite pure from that point of view, like you say. Though in humans...?
You could always try an a-typical approach like alpha 2 adrenergic blockade - you seemed to have an understanding of this receptor agonist vs blockade properties etc - Mianserin or Mirtazapine would be drugs of such a class.
Have you tried this? Any success? One of my degrees is in regular pharmacology, but that was a long time ago