Posted by iforgotmypassword on January 12, 2009, at 5:20:39
on ziprasidone (Geodon/Zeldox). i'm sorry i didn't reply, but i often put off messages because i'm stuck mentally and can't articulate, and then i lose track entirely and never finish the post.
i have had that problem on risperidone (Risperdal), pretty much exactly as you describe. a scary, and periodically urgent feeling that your breathing is being constricted strangely and is made worse in specific positions like lying down, and makes you worry about sleeping, because you worry you might stop breathing in your sleep if you aren't awake to remember to reinforce it. this happened to me in the hospital, and my doctor felt that it was due to the tendancy of some people to be more sensitive to the sedative effects of antipsychotics. even at the time, i suspected it was a sort of stiffening/warping extrapyramidal symptom. now i am sure of this, and this problem is brought up occasionally on the internet. it is related more to dystonia and parkinsonism (antidopaminergic issue) than tardive dyskinesia (development of dopaminergic receptor hypersensitivity). some doctors catch this and note it as the development of a dystonic reaction, i think it is likely most don't, which is unfortunate and scary.
i think problem this accounts for the "dyspnoea" entry on some antipsychotic side effects lists, and when recognized by a savvy doctors, it probably adds to the "dystonia" or "acute dystonic reaction" numbers instead, or additionally. it is too bad that we don't seem to see anything like "extrapyramidal dyspneoa" or "dystonic dyspneoa".
risperidone, ziprasidone and aripiprazole (Abilify) have high D2 occupancy. this almost seems ironic in the case of the first two as they are supposed to be the most selective for 5-HT2A (in the 5-HT2:D2 ratio) receptors out of all atypicals affinity-wise, but this does not translate to how things happen occupancy wise in the brain, whether because of a receptor types abundance, or characteristic receptor sensitivities, or who knows. with both risperidone and ziprasidone, D2 occupancy catches up very easily with 5-HT2A occupancy; with ziprasidone you can take a low dose and have 5-HT2A occupancy at say 80% but D2 is already up there at 50%, much higher that the 7:1 5-HT2:D2 affinity ratio would suggest. aripiprazole is even worse occupancy wise, D2 occupancy is always higher than 5-HT2 (its 5-HT2:D2 affinity ratio is an even 1:1), and despite it being a partial agonist, it apparently isn't meaningfully so in the striatum, where it acts more like an antagonist.
so this may explain why you had poor luck with ziprasidone and aripirazole. now, this leads me to wonder, when you were on quetiapine (Seroquel) do you remember having as much trouble? it has lower D2 occupancy at any given moment due to it's quick dissociation from the receptor (quickly on-quickly off), theoretically it is supposed to be able to occupy the receptor just long enough to have an antipsychotic but not long enough to cause extrapyramidal issues as frequently when compared to other antipsychotics, so it still reaches as many D2 receptors, it just never stays stuck to one for very long, leading to less D2 receptors being occupied all at the same time.
unfortunately ziprasidone and aripiprazole are pretty much the only antipsychotics in the united states that have a lower risk for significant weight gain, obesity, and diabetes, but if quetiapine works better for you, the option of taking adjunctive metformin (Glucophage) may be something to ask your doctor about. this can be a preventative measure that can help you from gaining more weight in the case that you do (but on it's own doesn't cause weight loss, again, just prevents futher gain when it works.)
drugs to watch out for in the future will be sertindole (so far only available in europe, hopefully this changes if the united states start caring about health care for the proprotionally less affluent) and pimavanserin (in stage III trials, i think.) i hope this combination gets researched in the near future, theoretically it may be the closest to a functional cure for schizophrenia, and it may allow many people to reclaim their lives, with few side effects or strange risks. (the only well-known risk with sertindole is the QT prolongation issue that can cause sudden death in rare cases, but theoretically a lower dose would be all that's needed in combination with pimavanserin, potentially eliminating that risk entirely.)
anyway, sorry this is long.
poster:iforgotmypassword
thread:873492
URL: http://www.dr-bob.org/babble/20090104/msgs/873492.html