I find a lot of auties/aspies do not react at all well to SSRIs.
Toady just got some more MXE, for when he eventually runs out of oxy. That will help blunt or prevent withdrawals. It seems to substitute well for oxy, or opioids in general, both in preventing withdrawals and as an analgesic. The NMDA antagonist properties helping stamp down on tolerance. Brilliant stuff for those uses.
As for GABA drugs, just wierd brain chemistry. Most GABA agonists just do not work on him properly. Weather GABAa modulators of GABAb agonists like baclofen. He has something wierd going on as far as adrenergic drugs go. He needs to take an alpha2 adrenoreceptor agonist to suppress jitters and akathisia. As far as his liver and kidneys, he had an abnormal liver/kidney test a couple of years back, but all that was was that serum albumin levels were just slightly on the high side of normal, nothing to worry about at all there.
He doesn't think his GABA drug issues are to do with tolerance, he doesn't use them that often at all. Mainly because they don't work properly. The doses he can take without phasing him whatsoever are quite rediculous, but how OFTEN he uses them, not very often, his scripts just mount up until he needs to take a huge great dose to do something so he always has plenty of spares. The amount of times he even uses his scripts for any of them at all is not very many.
The same goes for crosstolerant drugs like pregabalin. Never tried gabapentin, but pregabalin, even at several grams just does not get him high, and its not fantastic for his neuropathic pain either. Better than nothing, but not great.
Hopefully his MXE arrives soon, that way he can temporarily taper down his oxy until his next script is due. Withdrawals blow, but he isn't likely to have his pain fixed any time soon either. And of course he is physically dependent through having such long term pain. Toady just got referred to a pain clinic, as his docs don't know what the hell to do anymore. Really quite annoying. He would prefer being switched to a pain med with NMDA antagonist effects. Most countries keep at least one in their arsenal, that way he could knock the pregabalin on its head, he has loads of the stuff anyway. Just not this country, unless a racemic methadone brand is available.
As for fent, its notorious for downregulating MOR fast. Short acting, highly potent opioids or other drugs in general tend to produce a very rapid tachyphylaxis and are hard to maintain stably on even at regular, non-abusive doses. He had a problem with being on dihydrocodeine, getting regular scripts, due to its short duration of action. He prefers being on a long acting drug with a short acting one available to provide a small bolus dose with a fast onset when needs be.
Trying to get that done for the alpha2 adrenoreceptor agonist he takes, tizanidine, at the moment. He doesn't function well without, and wants to add in clonidine as his main drug of that class, with tizanidine available to provide a top-up dose to generally suppress his adrenal output when the clonidine proves not to be enough. At the moment he takes OCs and oxynorm, IR oxy for when it just doesn't give enough analgesia, a low dose of IR oxy tends to make all the difference dealing with his chronic pain while the OCs provide a steady long term state.
He just has half his OC supply as usual, which is going to be a nuisance, but MXE will take care of that. A downregulated parasympathetic nervous system is an interesting theory salat, it might just tie in with having to squash noradrenergic/adrenergic output as a theory not too badly.
Early stress...oh he has been through way too many highly stressful experiences, repeated false arrests, doing jail time etc. Hence his PTSD.
Tanshinone IIa Alleviates Hypoxic Ischemic Brain Damage.pdf