Antipsychotic-resistant 'voices'

[dopamimetic]

Ok, this is a hard bite to write about and, unless absolutely necessary, no way ever that I would talk openly about to anybody in real life because of stigma and people flat out treating you like a fool, twisting words in your mouth and attributing everything to 'tha illness'.

Sometimes I get something probably similar to hearing voices. It's not full voices but a second stream of thought, sometimes echoing my thoughts, sometimes answering to them or giving me more or less helpful advices. Kinda like if that 'inner voice' of conscience got decoupled and put into a half-baken AI of it's own. Hard to understand for myself and I don't expect you to be able to.

I don't fully know what to blame for (myself, yeah) - nmda antags together with dissociatives, heavy sleep deprivation & chronic stress triggered it, the junkie fool I am didn't stop (as acute disso use helps but things come back on rebound) and now 200mg DXM are enough, curiously I could continue to use lower-ish doses of arylcyclohexylamines without problems but more strange is that 100mg of memantine, a full D2 agonist and nmda antag doesn't trigger either. Nor do therapeutic doses of d-amph.

Antipsychotics do shit. Risperidone even triggers, most of them make me anhedonic and at danger for dyskinesia and panic. Tried quetiapine, chlorprothixene, risperidone, olanzapine, aripiprazole and some more but none of them helps shit besides the sedative side effects of some.

What does help are GABAergics, benzos, even ethanol but no way that I would use a benzo daily given the horrible anxiogenic withdrawal.

Now, these voices aren't really chronic. They stay quiet as long as I don't overdo drugs but usually wake up before I fall asleep (something which I read that quite some people get, independent of so called shizo but forgot the name). It's irritating and would love to have something against, but admitted it's mostly a search for a way to continue (ab)using nmda antagonists. With the current intensity I can live and it doesn't appear to increase, if anything then things get better with time.

But what does this mean? Psychotic symptoms which don't respond to any of the antipsychs, which remain isolated and don't escalate to paranoia or other hallucinations, etc.
From skimming through papers I think that over use of NMDA antags destroys GABAergic interneurons. Could sodium valproate be indicated here, or pregabalin?

What might offer protection, a benzo (GABA PAM) or something like picamilon (precursor) or even clonidine (unrelated but norepinephrine is involved in 'nmda antag neurotoxicity')?

It seems like norep might be a part as venlafaxine exacrebates the symptoms but I'm not sure.

Went to rehab over a year ago because of this, didn't tell about voices but other symptoms (irritability etc) for which they tried multiple antipsychotics. Finally continued on morphine which appears to both help and worsen, can't explain it better for now. Relapsed with K pretty soon and while the afterglows were replaced with depressive ones, I failed to see any relation between its use and the symptoms as long as I was below, maybe 120mg/d of morphine - or DXM was involved. Something weird about this substance for sure, heard others who tolerate K say it's toxic and it isn't sigma as noscapine doesn't trigger and memantine is a sigma agonist too.

Edit: Kappa!? Yeah, salvia does trigger. (Oh yeah, I'll make the correct pretty reckless impression.. ) So, buprenorphine??

Memantine, strangely, is the best I found yet. Helps with irritability, anhedonia etc and even at multiple times the recommended dose, enough to get hyperactivity and OCD, no hallus at all. But can't get it at the moment.

Any ideas?
Please don't tell me to stay away from any drugs, it drives me to suicide. Need some aid to cope with being completely lone, no job, home, friends. Am on kratom now which helps maybe 20%.

 

[dopamimetic]

Pushy.

I know, "not intended to diagnose treat cure or prevent any disease". Just don't know where else to ask for, the really educated profs are out of reach for somebody like myself and I know what I'll get if I talk to a random doc - antipsychotics, in decent doses, which neither work (for my case) nor do I want their side effects.

Possible that it's norepinephrine!? Don't just say no, it is involved in NMDA antagonist neurotoxicity and quetiapine helps in low-ish doses (<100mg where it is mostly selective for H1, alpha2C and to lesser extent alpha2A and 5HT2A but not enough to really antagonize D2) while venlafaxine causes worsening at >100mg (where its NRI mechanism becomes more prominent, it's still far too little for as DRI and as said, memantine does not trigger the symptoms).

Have to say that I suffer from heavy PTSD and recurring violent nightmares and waking up while physically speaking or screaming, which is pretty distressing and embarrassing. Also the 'voice' phenomenon doesn't occur when I am relaxed, only sometimes in moments of stress - and before falling asleep, which somehow is associated with stress too since a while.

This:

The central noradrenaline system, like the peripheral system, mediates the alarm reaction during stress. Overactivity of the system increases the arousal level and amplifies the emotional reaction to stress, which could manifest as a cluster of symptoms, such as insomnia, anxiety, irritability, emotional instability and exaggerated fear or aggressiveness (hyperarousal symptoms). Underactivity of the system lowers the arousal level and attenuates the alarm reaction, which could result in hypersomnia and insensitivity to stress (hypoarousal symptoms). Clinical data support the hypothesis that, in functional psychoses, the noradrenergic dysfunction is in fact associated with the arousal symptoms described above. The antinoradrenergic action of anxiolytics and antipsychotics can explain their sedative effects on the hyperarousal symptoms of these disorders. The results of animal experiments suggest that excessive stress can be a cause of long-term noradrenergic dysfunction. Source

But NE actually increasing synthesis of GABA!?

Norepinephrine pathways appear to modulate synthesis of GABA in central limbic stress circuits. Decreases in GABA synthetic capacity suggest reduced activation of stress-excitatory pathways and enhanced activation of stress-inhibitory circuits, and is consistent with a role for GABA in the antidepressant efficacy of NE reuptake inhibitors. Source

If we forget the schizophrenia-is-mediated-by-too-much-dopamine stuff for a moment, could it be possible? That NE exacerbates whatever toxicity my disso over-use caused, or maybe even not directly related to them?

 

[AlphaMethylPhenyl]

Okay, so I didn't read all of this very critically. I'll try not to be the whole "get off of drugs" type, nor pushy on what to take.

Venlafaxine is effectively an SSRI until about 300mg, that's why it's indicated for various anxiety disorders. Bridging on that topic, what about SSRIs? What sort of effect may they have? Because, in addition to benzos, they are indicated for anxiety, which you seem to find some relief from by using benzos.

There's definitely controversy, but my intel relates that benzos do work longer-term. Abusing them is no good, though, as I'm sure you know. Just want to say that they're not useless. Sometimes they're given as-needed, too.

In a lot of patients, not all, the voices can't be gotten rid off. But they reliably can be diminished so that they aren't so threatening. People learn to acclimate to them. Not saying this is your case, but it does happen.

If you think this is caused by too much NE, then maybe you could try clonidine, which effectively reduces the amount of NE that your neurons release. It's usually given for opioid withdrawal, as opioids tend to inhibit the release of NE. But if it were solely related to NE, you probably wouldn't experience much of a benefit from kratom.

I think there is an indirect relationship between NE and GABA, as one is excitatory, and the other inhibitory. But monoamines and amino acids tend to work on different circuits, if I recall right. For one, GABAa receptors are ionotropic, while NE binds to metabotropic receptors.

Definitely NE combined with dopamine would lead to psychotic symptoms more so. A thing to remember is that they're closely structurally related, which is why very high doses of, say, SNRIs, work as DRIs partly as well.

Quetiapine has a pretty active metabolite that's an NRI.

It's not surprising that stress worsens things. Stress worsens the symptoms of mental illness.

It sounds like NDMA antagonists aren't your friend, at least anymore.

 

[ions]

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