xelios said:Holy shit. I'm so gonna keep complaining until I'm off this one or at least at a dose where I'm not desperate enough to eat out of the garbage. Even 25mg puts me to sleep (I have insomnia for years) but she claims I'm on more for my mood, which I understand. I guess to prevent hypomania. But seriously, you have to weigh the side effects with the benefits.
Since it might interest you, atypicals don't work in a very strait-forward, dose-dependant way. Higher dosages aren't just stronger, they are entirely different drugs with entirely different effects.
Seroquel is a great example of this, when the guys at AstraZeneca were developing quetiapine, they were targeting schizophrenia and BPD-mania and settled on a molecule that's promiscuous, meaning it has affinity for several noteworthy receptors. The molecule, by design, hits H1 (histamine) very hard; it's a good target given the coupling between mania, activation and insomnia. It has 40X the affinity for H1 than D2/D1, the dopamine receptors which are the ultimate target of neuroleptics and the basis of treating psychosis. So, imagine if there is 1 dopamine receptor and 1 histamine receptor sitting around and in pops one molecule of Seroquel, where will it go? Turns out, it's 40X more likely to be in the histamine one, making you sleepy. To have an effect on dopamine, you basically, need to fill the higher affinity pool of receptors until there is enough free Seroquel to bind (probabilistically) to the lower affinity one.
In fact, before the molecule can influence dopaminergic signaling to an appreciable extent (between 60 and 80% occupancy), they need to occupy not only the histamine receptors, but then a1-adrenergic (dizziness, weight gain), then 5-HT/Serotonin (mood-ish), and finally D2/D1/etc...
So, that's why 25mg of quetiapine will put you to sleep, but 800mg will not kill you. From 25 to 50mg is a big jump in sedation, but going to 400 to 800 isn't since you've already saturated your histamine receptors and have moved to occupying a1 and then 5HT and finally D1/D2/Dx with the circulating drug. And actually, many become less sleepy due to activating effects downstream of the lower affinity receptors. Here's the question to be completed at home is: if your molecule of quetiapine is bound to H1 and not a dopamine receptor, is the drug really acting as an antipsychotic?
The take home is that saying your p-doc had you on Seroquel and it didn't work means nothing. The real question is at what dosage?
In terms of using it as an antidepressant adjunct, the AstraZeneca reps and researchers (in no specific order) claim it's due to inhibiting the norepinephrine transporter. IMHO, the jury is still out on that one as occupancy of NET is quite low at the 150 and 300mg levels they submitted to the FDA. Yet, AstraZeneca has data showing it's useful down to 50mg. And at only 25mg, you're popping the finest anti-histamine around! Sleep up!