Posted by Elizabeth on February 14, 2002, at 16:01:49
In reply to Re: Which antidepressant is right for you?, posted by torenada on February 10, 2002, at 12:12:52
> But, that is exactly my point. =) There are so many unknowns involved that we can't possibly know except by trial and error. That is why I said I don't believe it is right to ask someone if a particular drug will work for you or to recommend one to someone else. There is just no way of knowing until you try it.
I agree; one person's experience alone doesn't predict anything about how another person will respond to a drug, and I do often find myself having to point that out to people here. It especially troubles me when one person tries to scare someone else out of trying a medication that could help because of a potential bad reaction that really isn't that common.
I thought you might be interested to know that the theoretical reasons that you suggested don't really predict drug response, either. Let's say that person A has major depressive disorder and responds well to drug X, a drug that primarily affects, say, norepinephrine (for example, a tricyclic antidepressant -- a NE reuptake inhibitor). Now, person B might have major depressive disorder too, but as you've said, that doesn't mean person B will respond to drug X. Now let's say that person B tries drug X and it doesn't help much. Person B might find that drug Y, a drug that has a different effect on the same neurotransmitter (for example, an autoreceptor antagonist, such as Remeron) works better. Person B might even respond drug Z, a different drug that seems to have similar effects to drug X (for example, a selective NE reuptake inhibitor like reboxetine, or a different tricyclic AD). So it's not simply a question of which neurotransmitter to target. Drugs X, Y, and Z may have other effects that we don't know about, including effects on other neurotransmitters -- perhaps even ones that we don't know exist (so we can't study the drugs' effects on them, obviously). Or person B might need a drug that works differently on the same neurotransmitter because persons A and B have two different problems with the same system. Their responses may not even indicate that either of them has a problem with NE -- the effects of the drugs on NE might have different *indirect* effects on other neurotransmitters (perhaps on two different neurotransmitters). Persons A and B may even present with the same symptoms (e.g., a particular subtype of depression, such as melancholic depression) but respond best to different drugs.
Serotonin, norepinephrine, and dopamine definitely aren't the only neurotransmitters involved in the regulation of mood and other things that become dysfunctional in depression (such as sleep rhythms, psychomotor activity, ability to experience pleasure, basic drives or appetites (for food, sex, etc.), levels of energy and motivation, and so forth.
To give an example: I have recurrent major depression, and by my symptoms, it would be expected that I would respond best to a tricyclic antidepressant, MAOI, Effexor, or Remeron (these share the property that all of them are noradrenergic drugs; they've also been tested in depression that has symptoms like mine and found to work well, probably better than SSRIs). I had partial responses to a tricyclic (desipramine) and monoamine oxidase inhibitors (phenelzine, tranylcypromine, isocarboxazid). I'm taking 225 mg of Effexor now, and so far it seems to be working about as well as the TCA and MAOI drugs worked for me. The type of drug that really alleviates my symptoms is not a monoaminergic drug at all, but one which activates "mu" [the Greek letter] opioid receptors, an action shared by certain natural neuropeptides called endorphins and enkephalins (the "endogenous opioid system" or EOS). This drug and other mu agonists have a "paradoxical" stimulant-like effect on me and help with several symptoms that the monoaminergic drugs haven't seemed to do much about: anhedonia (a core symptom of depression), motivation, and concentration, in particular. I've been taking this drug along with Effexor for a couple months now, and the combination seems to be the best treatment I've come across. Perhaps I don't have enough endorphins or enkephalins, or perhaps there's some other problem with my EOS. On the other hand, it might be that whatever's wrong with my brain may not have anything to do with the EOS or with monoamines; it may just be corrected or compensated for *indirectly* by modifying these systems.
(I don't think that there are any drugs available that are known to activate the EOS in other ways. I know that there were once some efforts to find "enkephalinase inhibitors," drugs which would inhibit the metabolism of enkephalins, analogous to the action of MAOIs on monoamines. This idea was blown to pieces when the researchers discovered that the "enkephalinase" enzymes which catalyze the metabolism of enkephalins are involved in the metabolism of many other neuropeptides and would be unusable as medications due to these extremely widespread, global effects.)
My understanding is that, most likely, the problem in psychiatric conditions has to do with neural pathways in specific parts of the brain, and not with a global lack of any specific neurotransmitter. For whatever reason, taking medications that increase the amount of different neurotransmitters (or otherwise affect neurotransmission) corrects these pathways (just how or which pathways, we don't know), but because the effect is global, other pathways are also altered, which can lead to unwanted effects (e.g., the abnormal stereotyped movements often caused by dopamine antagonist drugs, which are the result of blockade of extrapyramidal neurons that control rhythmic movements). Because we don't have the technology to make medications affect only the desired parts of the brain, the effects of antidepressants and other psychotropic drugs are often widespread. There has been some research on treatments that target a specific location (or send medication to a specific location) using electrical stimulation, magnets, and the like, but this isn't something that we can use to treat psychiatric disorders at this time. There are also some medications that have relatively specific effects, but we don't yet know just how to design medications to target specific receptors, much less specific receptor subtypes that are thought to be involved with particular conditions. Simply increasing the amount of a naturally occurring chemical (by triggering release, blocking reuptake, inhibiting metabolism, etc.) won't target a particular receptor subtype, since these substances are nonselective agonists at their own receptors (for example, serotonin activates all the subtypes of serotonin receptors).
(Incidentally, it certainly hasn't been proven, as many people seem to believe, that a "chemical imbalance" is responsible for such mental disorders as depression, bipolar disorder, anxiety disorders, and schizophrenia. The expression "chemical imbalance" doesn't even have a clear meaning. I love those goofy Paxil commercials that claim the drug corrects a "chemical imbalance" which "could be to blame" for generalized anxiety.)
Okay, that was just another diatribe. We now return to your regularly scheduled posts.
-elizabeth
poster:Elizabeth
thread:93221
URL: http://www.dr-bob.org/babble/20020208/msgs/94140.html