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Re: Finally trying vortioxetine -- initial impressions SLS

Posted by undopaminergic on December 28, 2022, at 18:16:37

In reply to Re: Finally trying vortioxetine -- initial impressions undopaminergic, posted by SLS on December 28, 2022, at 17:01:55

> Amisulpride *might* be more effective for depression than sulpiride. Its anti-dysthymic properties are supposedly well-established. Like sulpiride, low dosages effect more of a pro-dopaminergic effect than high dosages. This is likely because presynaptic autoreceptors have a higher binding affinity to dopamine than postsynaptic receptors do. This yields a net increase in the release of dopamine. The dosages that I have seen quoted most often to treat dysthymia and depression are 25-50 mg/day. Much higher dosages of amisulpride are needed to treat schizoid or psychotic conditions. Since you have already tried sulpiride with inadequate results, I doubt it makes sense to try amisulpride at this juncture.

I know all that stuff about autoreceptors, etc., it's what made me try sulpiride in the first place. I also tried amisulpiride, and it did not have an effect, but that was after sulpiride stopped working.

Tentatively, selegiline seemed to work to restore the responsiveness to the stimulant effect. I propose that the "amphetaminergic" effects of selegiline, ie. the increased dopamine release, re-sensitised the autoreceptors. By contrast, blocking them seems to desensitise them. I know that seems backwards, but it's my best theory.

I'd put my theories to test, but currently do not have access to selegiline or amphetamines.

> What about adrafinil? I believe that's available in Europe. People who tried both adrafinil and modafinil here on Psycho-Babble preferred adrafinil, and were willing to import it.

I tried adrafinil, but did not notice any benefit (nor any side-effects).

I've tried modafinil, but not the original (Provigil, Modiodal), and there seems to be a difference between different forms of modafinil.

> My first dose of sulpiride made me feel great. However, the improvement dissipated within hours and never returned, despite continued treatment.

Could you restore the effect through abstinence or through the use of amphetamines?

> I am unclear as to what condition(s) you are dealing with. Would schizoaffective disorder be an applicable term?

I'm bipolar and have had some trouble with psychosis. Technically, as far as I'm able to interpret the DSM, it's not schizoaffective because a mood episode has always been present at the time of the psychotic symptoms. However, taken more liberally, you could say it's schizoaffective because depressive episodes are not involved etiologically in the psychoses. Manic episodes are (involved), due to the loss of critical thinking. But the delusions tend of persist beyond the extent of the manic episodes.

Anyway, the diagnostic technicalities are less important than finding relief from the symptoms that bother me, and that is depression that manifests not so much as low mood as anhedonia, apathy, and cognitive impairment.

> I recommend that people make a list of what drugs made them feel better, regardless of magnitude or duration. Then make a list of those drugs that made you feel significantly worse where the worsening did not dissipate quickly. Which drugs were totally inert, and that you would not mind revisiting. Then you can look for commonalities, synergisms, and complementarity between drugs. You can choose which agents to combine based upon your previous experiences with them empirically and what you know about their pharmacology. I usually take into consideration empirical observations first and pharmacology later in the selection process.

One of the only drugs that made me feel worse was methoxetamine, which was very dysphoriant. More typically, people get euphoric from it. And memantine made me feel great. Both are NMDA-glutamate receptor antagonists.





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