Posted by PeterJ on May 19, 2000, at 20:37:35
In reply to Re: Cam--Serotonin-modulated pathways?, posted by SLS on May 19, 2000, at 13:25:10
> Question: Do you think that the prefrontal cortex is involved in SSRI-induced apathy through the stimulation of 5-HT2 receptors located there?
>
> Do you think it is feasible to use small doses of a 5-HT2 antagonist to deal with this? (Remeron, Serzone, Periactin...)? Has anyone described such an effect?That's an excellent idea. The usual explanation for SSRI induced apathy is that SSRI stimulation of 5-HT2 receptors on DA cell bodies inhibits firing of DA cells which project to (voila!) the frontal cortex. So bromocriptine has been used to treat the apathy with anecdotal success. The apathy is often compared to ADHD. SSRIs sometimes worsen ADHD.
A direct opposition of the effects of DA and 5-HT projections has also been hypothesized, but I don't know if it's been proven.
In either case, using a 5-HT2 antagonist makes perfect sense, and I don't know why it hasn't been tried. 5-HT2 antagonism helps the apathy of schizophrenia ("negative symptoms") and has anecdotally helped SSRI sexual dysfunction (sexual apathy) in a few cases, but I haven't heard of its use for SSRI apathy per se.
BTW, a great drug that unfortunately never got approved was the 5-HT2 blocker ritanserin. It was a pure 5-HT2 antagonist unlike the current 5-HT antagonists which all do something else (DA blockade with Risperidone and other antipsychotics, and several receptor effects with Nefazodone and Mirtazepine...). Ritanserin didn't quite make the FDA cutoff point in antidepressant studies. Too bad for those who might respond to it. It's also great for sleep. It increases deep slow wave sleep. I talked to the drug company that made it and they told me they tried but couldn't get it approved for sleep disorders because, according to the FDA. "there is no such disorder as lack of slow wave sleep."
> The more of the posts I read between you, PeterJ and medlib, the more of a dummy I feel like. I think this is a good thing. It helps me to remember how educated I am not.
"The sense of worthlessness or guilt associated with Major Depressive Disorder may include unrealistic negative evaluations of one's worth...(Criterion A7)"---DSM IV, Mood Disorders, p. 321.
Peter
poster:PeterJ
thread:33678
URL: http://www.dr-bob.org/babble/20000517/msgs/34064.html