What did we learn from people restarting/microdosing SSRI?

[garycooper]

1) First, some people have fully/almost fully recovered. Therefore, the whole idea that there is permanent damage is problematic in itself, despite obvious evidence that a lot of stuff is fucked up in our bodies.

2) Some people have recovered using other SSRIs than those that gave them PSSD.

3) Some people have recovered after microdosing the same SSRI that gave them PSSD

4) Some people have had short windows of recovery after restarting the same SSRI that gave them PSSD.

5) We add this to the known fact that many people on this forum took multiple different SSRI, stop them without incident (which is probably what happens to most users), restarted a different one, and developed PSSD while on it/stopping it/changing dosage. Which is quite crazy/paradoxical when you think about it… How come your body knew how to recover from Prozac but not from Paxil?

So I’m wondering if the solution would be hidden in the different molecules, and their different half-lives/different modulation of the serotonin receptors. SSRI have extremely long half-lives, but maybe some bodies react weirdly to long half-lives, while other reacted weirdly to shorter half-lives.

I’ve also being thinking : what if it’s not the SSRI the problem, it’s like rather the context that you were in when you developed PSSD? Like when you quitted cold turkey you’re body was deficient in some vitamin or mineral, and never recovered, and for some reason it stayed that way. Or you had a bad microbiome or were stressed or whatever.

[Meso]

That's a good question. My hypothesis is that SSRI intake causes desensitization of several serotonin subtypes and this resulted in a blunted glutamate neurotransmission, since serotonin heavily modulates glutamate. Microdosing any SSRI would result in activation of the desensitized receptors, causing glutamate neurotransmission to be partially restored, offering relief from PSSD. A strong proof in favor of this hypothesis is how alcohol hangover offers relief from PSSD as well, which is closely linked to a glutamatergic rebound, and how psychedelics also offer a window of relief through disinhibiting glutamate release via 5HT2A receptors.

Other hypotheses are: how SSRIs act to modulate estrogen receptors, acting like weak SERMs. And how SSRI reinstatement would partially restore the HPA axis through improving cortisol release via 5HT1 and 5HT2 receptors. But we still don't have solid evidence since studies on PSSD are scarce, sadly.

Personally, two SSRIs failed to give me PSSD and only one managed to do so (low dose Venlafaxine). There are certain differences between SSRIs. For example, Venlafaxine is similar structurally to Tramadol, so it could be interfering with opioid receptors, Paroxetine is an anticholinergic, Sertraline is a sigma-1 antagonist and a very weak DRI, Fluoxetine is a 5HT2C antagonist, etc.

All these targets can alter glutamate and/or the endocrine profile in a synergistic manner. This synergism is similar to how, for instance, stimulants + NMDA antagonists can trigger as acute psychotic episode whereas either alone wouldn't trigger it, depending on the person. Just food for thought.

[naiverat]

Alcohol has almost always been super beneficial to my sexual function (both at the time of ingestion and the next morning). Too bad alcohol acts on so many different systems. I like your theory, though, Mesolimbo. It's consistent with my observations.