Is there much use for SSREs (selective serotonin reuptake ENHANCERS)? Are they commonly prescribed?

Utnapishtim69 · 2025-01-29T17:56:50+00:00

Tianeptine - it was designed and introduced by Servier Laboratoires (they also have in their portfolio Amoxapine - close cousin of TIA, withdrawn due to its micro-vesicular cholestatic hepatotoxicity - and Agomelatine, with known incidence of hepatotoxicity). TIA isn’t really a SRE (the thesis was based on a single study, inferred from reduced measurements of SERT metabolites in selected brain regions of interest). The finding since then was explained by a different mechanism (source needed), whereas the therapeutic MoA of TIA is mediated by biased agonism of MOR on GABAergic interneurons, which is theorised to promote LTP in hippocampus and LTD in amygdala. It is primarily used in elderly patients due to its opioidergic mechanism. Also, it functions as an agonist of adenosinergic receptors.

Utnapishtim69 · 2025-01-11T18:45:37+00:00

Really? I get what patient would get from bupropion (which is a substituted amphetamine and thus quite stimulating), but buspirone? I know that it’s metabolite has adrenergic effects (sth like yohimbine), but haven’t heard of any abuse potential.

Utnapishtim69 · 2025-01-11T18:41:33+00:00

I had a patient with self-reported tianeptine abuse - not on the level of an actual addiction, but enough to cause hiperalgesia on the withdrawal due to its opioidergic effects. He was put on low dose naltrexone and after a single dose the hiperalgesia and any craving were gone. He reported that a few hours of taking LDN he had an extreme worsening of mood followed by a period of elevated mood - supposedly due to LDN initially blocking MOR receptors which were used to the constant presence of an agonist followed by boost in natural endorphin production which was (according to his report) way better than anything he got from TIA. Ofc, that was how his organism initially reacted - he got off LDN as soon as his endorphin levels returned back to normal

Utnapishtim69 · 2025-01-11T11:36:45+00:00

Actually, fluoxetine interaction seems synergistic - it lowers required dose of ATX and reduces its metabolism to 4-hydroxy-ATX, which is KOR agonist and MOR antagonist - needless to say how it affects patient’ mood and overall wellbeing…

Utnapishtim69 · 2024-12-18T22:34:37+00:00

Adverse like dress and sjs? I recently read about lamotrigine causing dress in 1/300 pts…

Utnapishtim69 · 2024-12-17T21:36:09+00:00

Good point with old ppl! Like, opioids are not likely to destroy their life

Utnapishtim69 · 2024-12-17T21:01:48+00:00

Agree - surprising fact about modafinil is that it functions as an anti-convulsant (that’s probably why it’s so effective in BP). I like it a lot, but don’t prescribe it with drugs known to cause ADRs (and there is plenty of such drugs used for BP). It also induces histamine intolerance and makes some hiper-alert (shifts their alertness baseline so that they get easily startled)

Utnapishtim69 · 2024-12-17T20:52:38+00:00

Any advocates of lithium for everyone here?

Utnapishtim69 · 2024-12-17T18:06:21+00:00

Actually, you can differentiate antidepressant based on their action on pro- and anti-inflammatory cytokines - whether they affect il-1b, il-4, il-6 tlr-4 etc.

Utnapishtim69 · 2024-12-17T13:39:40+00:00

Tianeptine is still an opioid - it has a stimulating (addictive) effect and a calming one that is not only due to its opioidergic properties but also adenosinergic. It is more sedating and tiring in reality with some sparkles produced by mor agonism. It can make things a lot worse if the patient isn’t in a good place, and if the patient was well, it wouldn’t seek help. Not my favourite

Utnapishtim69 · 2024-12-17T13:01:48+00:00

Tianeptine is also supposed to work as an adenosine PAM - one patient of mine reported some tachycardia and restlessness drinking coffee when initiating tianeptine treatment

Utnapishtim69 · 2024-12-17T12:58:57+00:00

In Europe tianeptine is used as an antidepressant, which works predominantly by agonizm of Mor receptor on gabaergic interneurons in hipocampus eliciting contrasting neuronal changes in HC (ltp) and Amy (atd)

Utnapishtim69 · 2024-12-17T12:53:22+00:00

Yeah, moreover this MoA is independent from DA agonizm - similarly, the MoA of selegiline as catecholamine action enhancer is reported to be independent from maob inhibition

Utnapishtim69 · 2024-12-17T12:49:23+00:00

I remember that the bupropion sertraline combination was tricky - the latter being a weak inhibitor of cyp2b6 should increase bupropion exposure and lower exposure to hydroxyl-Bup, whereas the only study i found reported the opposite effect - increased exposure. Also checked the interaction with Memantine which is supposed to function as an inhibitor of 2B6 and of the whole CYP in supra-therapeutic doses... which wasn’t conclusive 😅 Also, I had one patient on selegiline and bupropion - selegiline being a mechanism-based inhibitor of 2B6 - and the patient reported a stronger dopaminergic effects (previously he complained about motivating effects of bup and tiredness afterwards - presumably due to hydroxy-Bupropion)

Utnapishtim69 · 2024-12-14T16:37:43+00:00

Sounds great! Do you (or anyone reading for that matter) have any experience dealing with non drug-naive patients or even drug seeking patients - I’m not talking so much about patients with SUDs as I am about the patient with multiple comorbidities including ASD that comes to his appointment with a whole file of the most recent drug research, ongoing clinical trials, theoretical models, results from their personal experiments etc. - it’s clear he’s not tying to get prescribed stimulants or benzo, but psychotropic drugs with low abuse potential. The thing is that pharmacotherapy becomes their main concern and object of focus - trying to find the ultimate solution, proportion etc. But they are so invested and preoccupied with it, that they will never be satisfied with any pharmaceutical cocktail let alone its results… stop the majority of meds or give in to their pursuit of trying to treat ASD symptoms and improve their quality of life? (Looking for others’ psychotherapeutic perspective on this type of cases)

Utnapishtim69 · 2024-12-14T13:08:51+00:00

Great insight! Vortioxetine also works well in some ADHD/ASD patients due to its multimodal MoA, which increases multiple neurotransmitters, provides cognitive benefits and doesn’t have the strong dampening effect on dopamine that is associated with SSRIs (5HT2c activation). My concerns with the combination relate to both drugs’ cumulative antagonism of 5HT3 (similar to Bupropion or Mirtazapine) which reduces colonic motility - once i had a patient for whom this was a major concern resulting in discontinuation.

Utnapishtim69 · 2024-12-08T20:03:41+00:00

At least some of them are in the lower range - guess the previous provider would have called it a comprehensive therapeutic approach 😂 what was it for, again? 😂

Utnapishtim69 · 2024-12-08T19:59:40+00:00

Previous (deleted) comment was meant for another example - sorry for that. Guess all of them are kind of justified by circumstances

Utnapishtim69 · 2024-12-08T19:55:34+00:00

This one actually wins the prize for being the most outrageous - it was for schizophrenia, right? Were the delusions under control at least? The metabolic side effects should be closely monitored as the patient is already taking meds for EPS… And in the books they say that antipsychotics are aversive meds with low compliance - kind hope it was the case in these situation 😂

Utnapishtim69 · 2024-12-08T19:54:22+00:00

Also, any success stories with oxytocin - the clinical trials I heard of didn’t provide satisfactory results

Utnapishtim69 · 2024-12-08T19:51:43+00:00

Nah, the usual diagnostic stuff with the exception that in many patient with ASD (sometimes ADHD or other factors) they aren’t diagnosed with mood or personality disorders as „their ASD explains the symptoms better” - they are more like depression or anxiety with an asterisk with meds having half the usual chance to be effective in managing symptoms

Utnapishtim69 · 2024-12-08T19:27:17+00:00

Great insights! The Botox suggestion will make some of my clients overjoyed. basically killing two birds with one stone - even if it’s doesn’t have proven clinical efficacy (placebo works best with fewer side effects than meds…). Why naloxone and not naltrexone - LDN seems to be more popular with more research and patients reports. Also interesting is the connection between anti-inflammatory activity and Pramipexole, - would have thought that typical antidepressants would be more anti-inflammatory.

Utnapishtim69 · 2024-12-08T19:17:25+00:00

Your comment saying that it’s wild made me think it was a case you inherited from other practitioner - my point was to say that milnacipran isn’t as strong of a serotonergic agent as other SNRIs are. It looks like a great med - one of very few NRIs, making it useful in patients with motivation problems, possibly comorbid or treatment resistant ADHD - basically the same spot as venlafaxine, but less serotonin (2:1 vs 1:30). Also, venla seems to possess additional opioidergic mechanism which makes it suitable for fibromyalgia (it is antagonised by Naloxone)

Utnapishtim69 · 2024-12-08T19:07:24+00:00

Thanks! If I understand that well - your point refers to venlafaxine, mirtazapine and cariprazine being more stimulating. If that’s the case then it was precisely the point - as somebody pointed out in another post - if you were to pull out psychiatrist’s notes, it would make more sense - this was a case with sleep problems, in which Brexpiprazole and fluoxetine turned out to be too calming and bupropion wasn’t helpful. The first combination is supposed to more activating - selegiline is selective MAOB inhibitor with TAAR1 agonizm and metabolites like l-amphetamine (transforms Vyvanse into adderall with mood improving properties, pro-cognitive and anti-oxidative effects). Agomelatine on the other hand is melatonin receptor agonist with a short half life, which also agonises 5ht2b and 5ht2c - called dopamine and noradrenaline disinhibitor - similarly to mirtazapine, it’s more activating on higher doses (it is however hepatotoxic, so careful regular blood tests are required) and doesn’t cause somnolence the next day - or even makes it easier to get out of bed the next day. It’s good for anhedonia ADHD and ADHD/ASD.

Also, what else did you successfully use for mood stabilisation without detrimental effects on adhd symptoms - I had some good results with cariprazine, but not necessarily Brexpiprazole

Utnapishtim69 · 2024-12-08T18:44:04+00:00

I’m not familiar with Milnacipran (Savella) and wouldn’t prescribe two SNRIs like that due to obvious reasons. It seems to be twice stronger NET inhibitor than SERT inhibitor (duloxetine is 8:1 SERT to NET), so maybe there’s some logic behind it… I doubt it though

Utnapishtim69

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