This week is a series of posts about depression, anxiety, family issues, and other brainweasels, for the people who have come on over from CaptainAwkward.com's various open threads. Hello, welcome, and feel free to comment here.
On the whole I consider myself fortunate that all of the very few drugs I've ever found that directly alleviate the depression, the anxiety, or both, are things I can only take episodically. They all knock me flat on my ass. If I take any of them, I have to block out 6-12 hours where I'm not required to do anything more complex than open water bottles and make myself peanut butter sandwiches. Leaving the house is definitely contraindicated. It's possible to go through life constantly, say, just a little bit drunk-ish -- but the problem with that is that you're always having to get a little bit more drunkish than you were the day before in order to cope, and that can snowball in a big hurry. Alcohol never did anything much for me, opiates don't actually work right on me (Vicodin does fuck-all except make me cry and itch in places I didn't know I had), and I was not impressed by pot, so there are three very bad plans eliminated right off the bat.
Officially, the only medication I have been issued is alprazolam, for acute anxiety episodes. I have what is nominally a 30-day supply that I actually refill about every 6-8 weeks. In most cases, long-term treatment with benzodiazepines is considered the very epitome of a bad idea, but I appear to be a weird case. I'm hypersensitive to the stuff, to the point where the standard 1mg of lorazepam they give you in the ER when you walk in after you've been having one long panic attack for two days straight actually made me yawp all over and then sleep for so long I'm informed a roommate came in to check my vitals. After about a week of this I showed no signs of habituation (i.e., I'd take one and 45 minutes later I'd be running into walls on my way to throw up again, like clockwork), decided that either I was allergic to the stuff or that was an OD for me, and went back to get something lighter. The only reason I have a bottle of 0.25mg alprazolam tablets now is because they don't make any smaller ones -- I break them in half, and they still make me reel around like a dozy wino. If I have to take one while I'm out, the very next thing I'll be doing is getting on the train home, and hoping I don't fall asleep halfway down the Red Line.
The standard first-line treatment for anxiety is SSRIs. I tried some and it was an adventure. If you've ever been dumb enough to take Dramamine or god forbid Benadryl on an empty stomach, multiply that times about a million, and then also realize that the anticholinergic side effects prevent you from finishing a goddamn thought, ever, and the akathesia prevents you from ever sitting still, never mind sleeping. I'm still missing most of my episodic memory from that little experiment; the bits I do retain are all the higher-level intellectual deductive stuff, like the time I looked at myself in the mirror and realized that my hair was clean, so I'd obviously had a shower sometime recently, but didn't at all recall having actually done it. All of the standard generic family of SSRIs were originally chemically derived from antihistamines like diphenhydramine, which itself has some minor anxiolytic properties, and in small amounts is a dandy sleep aid. I prefer it to the Xanax, in fact. I can deal with cottonmouth in exchange for not feeling hungover in the morning, and having a fighting chance of actually waking up when my alarm goes off.
I've tried some herbal things, like kava kava, which did work in the same manner as alprazolam, but gave me whacking great headaches, and the FDA warns of liver damage. I also tried valerian, which was reputed to work like benzodiazpines, but gave me the same side effects as the citalopram instead -- further research (after I gave the capsules to the rats, who regard it much as cats do catnip) instead reveals that there are some SSRI-like compounds in the stuff. If there is a better way to accidentally run a double-blind study on yourself, I can't think of one. Whatever is wrong with my brain is so obviously not connected to low serotonin levels that it isn't even funny anymore.
Unofficially, part of how I figured out that the anxiety problem was more physiological than anything else was that while I was in college, I got bored enough to take a whopping great amount of cough medication, just to see what happened. I would like to stress that even I did not at any point consider this a good idea. I just did a lot of research beforehand -- actual research, involving bibliographies and references to the New England Journal of Medicine and so forth -- and concluded that as long as I stuck to small recreational doses of stuff that only had the dextromethorphan in it, the idea was of insufficient stupidity to result in any damage. The conclusions, I came to later, and mostly because at this point I'm incapable of not using things to deduce other things. I used to figure out where one of my housemates had gone for the day by observing what he'd forgotten on the coffee table, ffs.
Pharmacologically speaking, dextromethorphan (DXM) is considered to be a dissociative hallucinogen. Most of the effects are actually induced by its metabolite dextrorphan (DXO). It is an uncompetitive NMDA receptor antagonist, binds to PCP2 receptors, and an assortment of sigma receptors. The NMDA and sigma stuff is where it gets its dissociative, dream-like effects. It's hallucinogenic only in the sense that if you sit very still and stare very hard at a fixed point, your brain begins to doodle patterns in whatever randomness or film-grain it sees there. The open-eye visuals are ephemeral and fragile -- blink and they're gone. If you're mistaking any of them for reality, either you've taken much more than I ever did, or you've got bigger issues than being high. If you lie there long enough, you tend to nod off a lot, and the closed-eye visuals are the sort of abstract self-modifying patterns you get from launching Winamp and running MilkDrop while your music plays. Reality comes back just fine if something pokes you awake. Although you are -- not stupid, exactly, but very abstract and circular in your conversation. If you hang around potheads, nothing about this part would surprise you at all. DXM tends to blur the distinction between levels of abstraction without necessarily diminishing your ability to juggle spatial details, though, which gives it an odd sort of popularity among mathematicians.
The more relevant interesting thing about DXM in my case is that the PCP2 receptor activity make it a sort of second-hand dopamine reuptake inhibitor -- except, unlike more commonly-known DRIs like cocaine and (meth)amphetamines, DXM and DXO seem to have no effect on GABA release or the GABA-pathways. GABA, or gamma-amino butyric acid, is the primary inhibitory neurotransmitter in mammals. It turns stuff off when it's not needed. Like, say, the panic response. Most stimulants do part of their stimulating by cranking the GABAergic systems way down, so that nothing in your nervous system ever gets tired and shuts the hell up. (Caffeine is also an unusual example in that it doesn't touch anything GABA-related until you get up over half a gram or so, in the caffeine-naïve, which is probably why caffeine is the only stimulant I've ever not found to be appallingly unpleasant. I still bear a grudge against the 12-hour "time-release" Sudafed formulation that wasn't.) Extra dopamine makes you feel generally less crap, and not shutting off the flow of GABA mean you don't sit there and jitter and scratch imaginary bugs out of your hair all night. DXM and its metabolites also appear to have no noticeable serotonergic activity, in contrast to the more commonly-known hallucinogens like LSD and psilocybin, so it never caused me the same bizarre problems as the antidepressants did.
(GABA receptors are what benzodiazepines like alprazolam act on. Shutting them all down indiscriminately is the part that makes you sleepy. I'd adore it if someone figured out how to either shut down just whatever is going on over and above normal, or quarter generic Xanax tablets without reducing them to powder. They taste absolutely terrible. I've asked about things that attack the problem from the other end, and stop the production of adrenaline, but for reasons I cannot fathom, no one will give me a bottle of cheap, generic, widely-available, un-recreational propranolol. The mind boggles.)
The upshot of all this is that about 5mg/kg of dextromethorphan HBr means I can't feel my toes for like eight hours, but I also can't really panic over anything. If anything does prompt the physiological panic response, I'm so decoupled from the concrete actions of my sympathetic nervous system it that it doesn't matter. The feedback loop where being in a state of high alert makes every subsequent anything push me into a state of yet-higher alert doesn't happen. I worked out a plan of attack for handling a lot of really shitty family problems while lying on the bed with one eye closed -- because you go all chameleon and can't focus both of them on the same point when the stuff kicks in -- half-watching uncomplicated films like Live And Let Die, which as far as I can remember, was about seventeen hours long, the time-dilation effects of DXM also being interestingly trippy.
Something about DXM also seemed to reset whatever controls the depression response, to the point where it wasn't uncommon for a bolus of the stuff to whack my brain more or less back into shape for the next couple of weeks. This led to the interesting observation, when I was attempting the SSRIs, that I was actually way more stable back when I was doing drugs. The humor tends to be lost on doctors, but further independent nosing around in the listings for NIMH research says that clinical trials have been underway in regards to ketamine producing a rapid remission of major depression in treatment-refractory cases. Ketamine works essentially like DXM only more; I haven't tried to get my hands on any, but it is available in medical-grade ampoules (it's still used as a veterinary anaesthetic, and sometimes in pediatric patients), so I suppose somebody at some point got a hold of some stuff they were positive was in fact ketamine and was much happier as a result, and pointed it out to science.
On the whole I consider myself fortunate that all of the very few drugs I've ever found that directly alleviate the depression, the anxiety, or both, are things I can only take episodically. They all knock me flat on my ass. If I take any of them, I have to block out 6-12 hours where I'm not required to do anything more complex than open water bottles and make myself peanut butter sandwiches. Leaving the house is definitely contraindicated. It's possible to go through life constantly, say, just a little bit drunk-ish -- but the problem with that is that you're always having to get a little bit more drunkish than you were the day before in order to cope, and that can snowball in a big hurry. Alcohol never did anything much for me, opiates don't actually work right on me (Vicodin does fuck-all except make me cry and itch in places I didn't know I had), and I was not impressed by pot, so there are three very bad plans eliminated right off the bat.
Officially, the only medication I have been issued is alprazolam, for acute anxiety episodes. I have what is nominally a 30-day supply that I actually refill about every 6-8 weeks. In most cases, long-term treatment with benzodiazepines is considered the very epitome of a bad idea, but I appear to be a weird case. I'm hypersensitive to the stuff, to the point where the standard 1mg of lorazepam they give you in the ER when you walk in after you've been having one long panic attack for two days straight actually made me yawp all over and then sleep for so long I'm informed a roommate came in to check my vitals. After about a week of this I showed no signs of habituation (i.e., I'd take one and 45 minutes later I'd be running into walls on my way to throw up again, like clockwork), decided that either I was allergic to the stuff or that was an OD for me, and went back to get something lighter. The only reason I have a bottle of 0.25mg alprazolam tablets now is because they don't make any smaller ones -- I break them in half, and they still make me reel around like a dozy wino. If I have to take one while I'm out, the very next thing I'll be doing is getting on the train home, and hoping I don't fall asleep halfway down the Red Line.
The standard first-line treatment for anxiety is SSRIs. I tried some and it was an adventure. If you've ever been dumb enough to take Dramamine or god forbid Benadryl on an empty stomach, multiply that times about a million, and then also realize that the anticholinergic side effects prevent you from finishing a goddamn thought, ever, and the akathesia prevents you from ever sitting still, never mind sleeping. I'm still missing most of my episodic memory from that little experiment; the bits I do retain are all the higher-level intellectual deductive stuff, like the time I looked at myself in the mirror and realized that my hair was clean, so I'd obviously had a shower sometime recently, but didn't at all recall having actually done it. All of the standard generic family of SSRIs were originally chemically derived from antihistamines like diphenhydramine, which itself has some minor anxiolytic properties, and in small amounts is a dandy sleep aid. I prefer it to the Xanax, in fact. I can deal with cottonmouth in exchange for not feeling hungover in the morning, and having a fighting chance of actually waking up when my alarm goes off.
I've tried some herbal things, like kava kava, which did work in the same manner as alprazolam, but gave me whacking great headaches, and the FDA warns of liver damage. I also tried valerian, which was reputed to work like benzodiazpines, but gave me the same side effects as the citalopram instead -- further research (after I gave the capsules to the rats, who regard it much as cats do catnip) instead reveals that there are some SSRI-like compounds in the stuff. If there is a better way to accidentally run a double-blind study on yourself, I can't think of one. Whatever is wrong with my brain is so obviously not connected to low serotonin levels that it isn't even funny anymore.
Unofficially, part of how I figured out that the anxiety problem was more physiological than anything else was that while I was in college, I got bored enough to take a whopping great amount of cough medication, just to see what happened. I would like to stress that even I did not at any point consider this a good idea. I just did a lot of research beforehand -- actual research, involving bibliographies and references to the New England Journal of Medicine and so forth -- and concluded that as long as I stuck to small recreational doses of stuff that only had the dextromethorphan in it, the idea was of insufficient stupidity to result in any damage. The conclusions, I came to later, and mostly because at this point I'm incapable of not using things to deduce other things. I used to figure out where one of my housemates had gone for the day by observing what he'd forgotten on the coffee table, ffs.
Pharmacologically speaking, dextromethorphan (DXM) is considered to be a dissociative hallucinogen. Most of the effects are actually induced by its metabolite dextrorphan (DXO). It is an uncompetitive NMDA receptor antagonist, binds to PCP2 receptors, and an assortment of sigma receptors. The NMDA and sigma stuff is where it gets its dissociative, dream-like effects. It's hallucinogenic only in the sense that if you sit very still and stare very hard at a fixed point, your brain begins to doodle patterns in whatever randomness or film-grain it sees there. The open-eye visuals are ephemeral and fragile -- blink and they're gone. If you're mistaking any of them for reality, either you've taken much more than I ever did, or you've got bigger issues than being high. If you lie there long enough, you tend to nod off a lot, and the closed-eye visuals are the sort of abstract self-modifying patterns you get from launching Winamp and running MilkDrop while your music plays. Reality comes back just fine if something pokes you awake. Although you are -- not stupid, exactly, but very abstract and circular in your conversation. If you hang around potheads, nothing about this part would surprise you at all. DXM tends to blur the distinction between levels of abstraction without necessarily diminishing your ability to juggle spatial details, though, which gives it an odd sort of popularity among mathematicians.
The more relevant interesting thing about DXM in my case is that the PCP2 receptor activity make it a sort of second-hand dopamine reuptake inhibitor -- except, unlike more commonly-known DRIs like cocaine and (meth)amphetamines, DXM and DXO seem to have no effect on GABA release or the GABA-pathways. GABA, or gamma-amino butyric acid, is the primary inhibitory neurotransmitter in mammals. It turns stuff off when it's not needed. Like, say, the panic response. Most stimulants do part of their stimulating by cranking the GABAergic systems way down, so that nothing in your nervous system ever gets tired and shuts the hell up. (Caffeine is also an unusual example in that it doesn't touch anything GABA-related until you get up over half a gram or so, in the caffeine-naïve, which is probably why caffeine is the only stimulant I've ever not found to be appallingly unpleasant. I still bear a grudge against the 12-hour "time-release" Sudafed formulation that wasn't.) Extra dopamine makes you feel generally less crap, and not shutting off the flow of GABA mean you don't sit there and jitter and scratch imaginary bugs out of your hair all night. DXM and its metabolites also appear to have no noticeable serotonergic activity, in contrast to the more commonly-known hallucinogens like LSD and psilocybin, so it never caused me the same bizarre problems as the antidepressants did.
(GABA receptors are what benzodiazepines like alprazolam act on. Shutting them all down indiscriminately is the part that makes you sleepy. I'd adore it if someone figured out how to either shut down just whatever is going on over and above normal, or quarter generic Xanax tablets without reducing them to powder. They taste absolutely terrible. I've asked about things that attack the problem from the other end, and stop the production of adrenaline, but for reasons I cannot fathom, no one will give me a bottle of cheap, generic, widely-available, un-recreational propranolol. The mind boggles.)
The upshot of all this is that about 5mg/kg of dextromethorphan HBr means I can't feel my toes for like eight hours, but I also can't really panic over anything. If anything does prompt the physiological panic response, I'm so decoupled from the concrete actions of my sympathetic nervous system it that it doesn't matter. The feedback loop where being in a state of high alert makes every subsequent anything push me into a state of yet-higher alert doesn't happen. I worked out a plan of attack for handling a lot of really shitty family problems while lying on the bed with one eye closed -- because you go all chameleon and can't focus both of them on the same point when the stuff kicks in -- half-watching uncomplicated films like Live And Let Die, which as far as I can remember, was about seventeen hours long, the time-dilation effects of DXM also being interestingly trippy.
Something about DXM also seemed to reset whatever controls the depression response, to the point where it wasn't uncommon for a bolus of the stuff to whack my brain more or less back into shape for the next couple of weeks. This led to the interesting observation, when I was attempting the SSRIs, that I was actually way more stable back when I was doing drugs. The humor tends to be lost on doctors, but further independent nosing around in the listings for NIMH research says that clinical trials have been underway in regards to ketamine producing a rapid remission of major depression in treatment-refractory cases. Ketamine works essentially like DXM only more; I haven't tried to get my hands on any, but it is available in medical-grade ampoules (it's still used as a veterinary anaesthetic, and sometimes in pediatric patients), so I suppose somebody at some point got a hold of some stuff they were positive was in fact ketamine and was much happier as a result, and pointed it out to science.
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