Let me know if weed ever works again. I have my doubts. I am just hoping for a cure so weed works again
Hey, I hear ya. It stopped working for me, too. I'll let you know the very first day it starts to work for me again. This syndrome has, effectively for me, thus far, been a total shut-off of all psychoactive substances. It's been a whole year thus far.
I’m 24 & I’m dependent on my grandparents, I live with them, only leave the house when my grandma takes me somewhere. I’ve got no job & there’s no way I could work in the condition I am in. She makes or buys all of my food. She also buys my nicotine & thc. I try to help around the house, but it’s really taxing on me, so it’s usually just simple things like doing a load of laundry or washing the dishes. They’re really supportive, but I wish I could do more.
I too, am tremendously dependent on my remaining nuclear family members. I too, have trouble helping out with chores where previously it was easy. Invegaishell mentioned trouble showering... and brushing teeth. I too have this problem.
I think it's important to bear in mind a couple things.
First, unless you had a few (same time of day) blood hormone tests in the years/months before you got paliperidone, you may never be sure if your prolactin and testosterone levels actually have returned to
your normal baseline. While they are obviously regarded as normal to a physician, the bell-shaped (normal distribution) curve they use to determine 'normal' covers a huge range of values. Your natural level(s) may have been quite different to what you have now, and so that may account for some of your subjective recovery issues.
Second, the testosterone (and prolactin) issue is only ever secondary (ie indirect) to Invega's primary mechanism (or blocking) of action on neurochemical signalling and the various long-term downstream/upstream effects that may have had on the brain's neural connections and CNS. And as you probably know, the neurochemical milieu that controls libido is very complex, not all about sex hormones, and something we know very little about.
We do know, however, that dopamine and norephinephrine appear to play a significant role in elevating libido, and serotonin in modulating it. We also know, for instance, that targeting the D3 receptor with drugs like Pramipexole, or D2 (and 5-HT2B, GLT-1 etc), as drugs like Bromocriptine do, can cause substantial elevations in libido, even in the absence of testosterone recovery (though long term, activation of D2/D3 can dampen or suppress prolactin signalling, leading to elevations in HPTA activity and thus testes output. Though it can also be harmful to GH and IGF-1 signalling, which have positive neuromodulatory effects, so swings and roundabouts!!!) Even drugs like bupropion can be helpful depending on the person, and that has quite a range of targets in the CNS that it modulates.
So what I'm trying to say, in a long roundabout way, is that the mechanism you're experiencing probably isn't really that mystifying. It's just that it still hasn't recovered, and may need some (temporary or long-term) pharmacological interventions by your doctors/specialists to kick it back into action and allow a more subjectively natural recovery
Thank you for your post. Your point about the distribution curve of normal values for hormones is very insightful--this never occurred to me. Unfortunately, I never did a testosterone nor prolactin test in my life before I did it after the onset of paliperidone syndrome, so I don't have that piece of information which really would have been insightful.
I thought about possible testosterone therapy even in spite of so-called normal levels, but have not explored it thus far. I imagine I will explore it soon, since the known options and outlook for treating low libido and sexual anhedonia are very limited and bleak. There's, roughly speaking, no accepted treatment for it. All of the psychiatric medications for it are off-label and informal. There also appears to be nobody really developing a treatment for it, either.
Compounding this problem is that low libido and sexual anhedonia induced by psychiatric medication is equally, if not even more bleak--
first, from antidepressants, particularly SSRIs, called PSSD (post SSRI sexual dysfunction, see
https://rxisk.org/post-ssri-sexual-dysfunction-pssd/), it's said, bluntly, that there is no cure or treatment,
and secondly, from antipsychotics--well, it's not even widely and properly acknowledged enough as even existing! (antipsychotic induced sexual dysfunction) I imagine it has the same bleak outlook as the SSRI induced variety.
I concur with you regarding the importance of dopamine and (at the very least, if not much more things) libido. Now, I did try pramipexole but was unable to take a high enough dose given some very irritating side effects. I was able to take a much higher dose of wellbutrin for a longer period of time (also with serious side effects). Neither of them worked but I'm still open to trying other dopamine agonists, hoping that I can tolerate a higher dose. My intolerable side effects to dopamine medications thus far could also be an indication that it may not be the problem, or, perhaps, that the specific dopamine actions of these types of drugs are just not what's needed. There are also dopamine-releasing agents as well as so called dopamine reuptake inhibitors sometimes used in the treatment of depression and anhedonia. These appear to be different from dopamine agonists.
I'm still of the belief that the dopamine hypothesis (as its antagonism is probably the most conspicuous element of paliperidone's stated pharmacology) is one of the best ones to explain the notorious features of paliperidone syndrome/NIDS, like severe depression/total anhedonia, sexual dysfunction (inc. low libido and sexual anhedonia) and loss of sensitivity to coffee/tea/caffeine. And I believe, like you said, it's just a matter of paliperidone's dopamine antagonism being so severe and long lasting that the receptors haven't recovered and standard dopamine medications haven't broken through yet (may need DRIs and DRAs instead of dopamine agonists, for instance). There could be another neurotransmitter related to dopamine pathways which could play a role in reviving/healing the dopamine systems, like GABA, norepinephrine and glutamate. I am partial to the hope that a combination of time and pharmalogical interventions could overcome it.
It just doesn't seem all that likely to me that most other neurotransmitters would be directly involved in these conspicuous severe adverse effects (unless, like I said, they are related to dopamine pathways).
For instance, paliperidone binds to the adrenergic and histamine receptors, too--it has occurred to me that that could be a treatment to explore, even though they seem to affect other physiological subsystems unrelated to depression-anhedonia and sexual dysfunction, etc.. The idea is this: reverse the effects of that adrenergic and histamine binding by introducing some drug that has the opposite action that paliperidone has on said adrenergic and histamine receptors. However, I'm not very clear on how the adrenergic and histamine receptors work in the first place, and I couldn't find any information on exactly what paliperidone does to them. I have considered mirtazipine as a possible candidate, since it has actions on the adrenergic and histamine receptors, but I still don't understand exactly what actions, and like I said, for it to be plausible as a treatment, it would have to be precisely opposite of what paliperidone does on them, and I can't ascertain what either of them do. I need to ask a psychiatrist with better neurochemistry chops, the likes of which I am trying to get into contact with. My current conventional insurance psychiatrists have proven to be lacking in neurochemistry chops and/or the motivation to exercise them and help the patient do the hard thinking. I might add, that my current psychiatrist, with sexual dysfunction expertise, upon my specific asking, told me that he was unsure of the neurochemistry behind, generally, low libido and sexual anhedonia, whether its dopamine or whatever other explanation.
Furthermore, although paliperidone is said to bind only to dopamine, serotonin, adrenergic and histamine receptors, it is possible that these themselves could have led to a neurochemistry cascade affecting other neurotransmitters. I hope to leave no stones unturned/turn over more stones in this regard and report back on the results.
However, you mentioned norepinephrine, and that peaks my interest. I have considered the importance of norepinephrine while slightly dismissing it. Particularly, I personally did not come across evidence for its strong role in sexual function, but I might have misread/not read enough and am going to do more reading. I am actually taking an SNRI right now, duloxetine (just started a week ago and working my way up from a small dose to the target of 60mg a day). I told my psychiatrist, "well, haven't I already taken a decently strong norepinephrine reuptake inhibitor in the form of wellbutrin?" And he told me that the norepinephrine reuptake inhibition action of duloxetine and, SNRIs generally, is stronger than that of wellbutrin. So we'll see!
