Posted by Elizabeth on December 2, 2001, at 17:04:00
In reply to Re: SSRIs and MAOIs for SP, posted by PaulB on December 2, 2001, at 14:03:07
> I understand. At the therapeutic dose Sertraline would block the serotonin re-uptake pump more powerfully than Prozac at its theraputic dose but not at Prozacs therapeutic dose.
I don't know that Zoloft is "more powerful" *or* "less powerful" a serotonin reuptake inhibitor than Prozac is, and that's certainly not what I was saying. They just have different equivalent doses.
> I believe, in my case that if there is little serotonin in the brain causing depression, anxiety and its various subtypes then blocking the re-uptake pump of just a few serotonin pumps will allow what little serotonin there is to circulate for longer at those few sites.
Oh dear, I seem to have confused you again. I'm sorry.
Okay, first of all, when you block serotonin reuptake, you block *all* the reuptake sites (transporters, pumps), not just some of them. This results in increased amounts of serotonin, because the serotonin is not being taken back up into the cells. (Remember: there's only *one* type of serotonin, although there are many types of receptors which the serotonin can interact with or "bind to.")
Serotonin receptors (not the same thing as the transporter or reuptake site) are *not* blocked by the SSRIs, although certain subtypes are blocked by non-SSRI antidepressants like Serzone (blocks certain 5-HT2 receptors) and Remeron (blocks 5-HT2 (not sure which subtypes) and -3 receptors).
Last, of course, it's pretty clear that the cause of depression (and anxiety) is not anything as simple as "too little serotonin." The extra serotonin is just the first step in a chain reaction which, ultimately, can relieve depression.
> With the SSRI's this is usually 5-HT1a, 5-HT2a and c and 5-HT3.
No; SSRIs do not affect a specific type of serotonin receptor.
> I was prescribed 75mg of the slow-release form of Effexor once a day in November 1999.
Okay. An interesting thing about Effexor is that it has some effects that aren't significant until you reach a certain dose. At 75 mg/day, it was probably acting as an SSRI. At higher doses, it starts blocking norepinephrine reuptake, and at still higher doses, it is a dopamine reuptake blocker too.
> I noticed a benefit after two weeks and this lasted for about 2 weeks before 'poop-out'. My physician did not think an increase in dosage would be beneficial.
That's peculiar, because it is known that Effexor can become more effective as you increase the dose, and 75 mg/day is not a very high dose (it's at the low end of the effective range). The maximum recommended dose is 375 mg, and some people go higher than that. So you weren't taking very much and possibly *could* have improved if you had taken more. Also, I think it is very possible that your brief improvement may not have been a drug response, but just a spontaneous temporary improvement.
> There is now much focus on substance p and its relationship with depression. The discovery of the first substance P antagonist (Cp-96,345) was made by scientists at pfizer.
It's not the first substance P antagonist to be studied for depression, but it still might prove to be useful. There are other approaches being tried as well, as you know. But just as a response to an SSRI does not mean that somebody's depression was caused by "too little serotonin," it's also true that a person who responds to a substance P receptor blocker (if these prove effective) does not necessarily have depression that is caused by neuropeptide deficiencies. And while the hypothalamic-pituitary-adrenal dysregulation in depression has been recognized for a long time, it's understood that this is not necessarily the cause of the depression.
> > >I would add that the newer MAOI's can be effective as the older 'irreversible' MAOIs if they are prescibed in very high doses.
> http://members.tripod.com/~cyberpsy/JWGTiller.htmThey work for some people with treatment-resistant depression (which is the special niche of the irreversible MAOIs), but moclobemide, at least, has a bad reputation -- it tends to be poorly tolerated, it often doesn't work, and when it does work it often loses effect.
BTW, 900 mg/day (the dose cited in the article you referred me to) is not especially high (many doctors go over the "recommended maximum") and I've known plenty of people who have taken higher doses. But at 900 mg/day or more, moclobemide often causes intolerable side effects. Agitation and insomnia seem to be paricularly common.
> Also you could go to mhsource.com site and look up an article entitled 'the Canadian Experience with RIMAs by Russell T.Joffe, MD, Psychiatric Times , June 1996, Vol X111 Issues 6
I think the title there is a bit misleading; perhaps "One Canadian Doctor's Experience with RIMAs" would be more appropriate.
RIMAs work well enough as a first-line therapy, and indeed, they are one (along with the SSRIs) in many countries, but their reputation is that they are not especially helpful for people who have treatment-resistant depression (i.e., people for whom a lot of other things have failed). Moclobemide is not an appropriate substitute for Nardil or Parnate, which are mainly used in treatment-resistant depression and anxiety, and it shouldn't be considered one.
-elizabeth
poster:Elizabeth
thread:85575
URL: http://www.dr-bob.org/babble/20011202/msgs/85825.html