Posted by Brainbeard on July 10, 2009, at 5:34:09
In reply to Prozac dosage questions, posted by garnet71 on June 30, 2009, at 19:36:58
Here's the pharmacology behind the effectiveness of low doses of Prozac: Prozac actually is a very strong 5HT2C-antagonist (blocker). The 2C serotonin receptor subtype normally inhibits dopamine (DA) and noradrenaline (NA) release. When these receptors are themselves blocked, they cannot inhibit DA and NA release. So, what happens when Prozac blocks 5HT2C-receptors? DA and NA release is 'disinhibited', which is a fancy way of saying they're boosted!
Prozac's 5HT2C-antagonism is so strong that at low doses of the drug (<5mg), 5HT2C-antagonism is probably all it does. At higher doses (~>5mg), serotonin reuptake inhibition comes into play, reaching full therapeutic effectivity at 20mg (stretched over a longer period of time of course due to accumulation of blood levels of the drug. With Prozac, always take into account that the drug has this ridiculously long half-life of about ONE TO TWO WEEKS, which measn it takes longer than A MONTH for the drug to leave your system). What counts for 5HT2C receptors, also counts for 5HT2A receptors. (There are differences, but the main mechanism is the same). Here, Prozac as well as all other SSRIs actually have a counterproductive mechanism: through raising serotonin levels, they ACTIVATE 5HT2A-receptors instead of blocking them. This may acutely lead to hightened anxiety and restlessness, and in the longer term to apathy, loss of libido, etcetera, which are all signs of a hypodopaminergic state [= too little dopamine].
It would be ideal to combine Prozac or any other SRI-therapy with a 5HT2A-blocker. Most TCA's (the older tricyclic antidepressants) have moderate 5HT2A-blockade. Most AAP's (the newer atypical antipsychotics) have strong 5HT2A-blockade. I have some Geodon coming my way which I mean to use low dose (5-20mg) for its strong 5HT2A-antagonism, in combination with an SSRI (Prozac or Zoloft, probably).A big part of the above is taken from Stahl; see: http://books.google.nl/books?id=cWbYxSfKN3cC&pg=PA532&lpg=PA532&dq=stahl+fluoxetine+5ht2c+antagonist&source=bl&ots=NpDHGZ0phR&sig=hZ-DC5qmtqj6lHgdwzN9nNgIELc&hl=nl&ei=fxNXSu_TE9Hw-Qb3jNjIDQ&sa=X&oi=book_result&ct=result&resnum=1; see also: http://www.google.nl/search?q=Are+All+Atypical+Antipsychotics+Equal+for+the+Treatment+of+Cognition+and+Affect+in+Schizophrenia%3F%3A+Schizophrenia%3A+From+Circuits+to+Symptoms&sourceid=navclient-ff&ie=UTF-8&rlz=1B3GGGL_nlNL255NL258 (this is a link to the reuslts of a Google search; click on the first search result - the article can't be reached through a direct link because it is a page for which you have to be subscribed).
Several other mechanisms also play a role with Prozac, and they have been neatly summarized (including links to the relevant research abstracts) by someone on a forum here: http://www.socialanxietysupport.com/forum/f30/some-interesting-stuff-i-just-read-about-fluoxetine-prozac-64674/
Hope this was helpful. Sorry for being elaborate. My meds made me do it! I've just started taking 10mg of Prozac myself, combined with Buspar. Buspar helps raising DA and NA levels even more (http://cat.inist.fr/?aModele=afficheN&cpsidt=2585906, confirmed by Stahl). I've been on 5mg of Prozac with 15-30mg of Buspar before, and this was a stimulating and antidepressant combo. I did have rapid weight gain though, presumably caused by the 5HT2C-antagonism..
poster:Brainbeard
thread:904045
URL: http://www.dr-bob.org/babble/20090709/msgs/905985.html