Me@nowhere.com wrote:
>
>John M. Williams <jmwilliams@enforcergraphics.f2s.com> wrote:
>
>>Me@nowhere.com wrote:
>>>
>>>On Tue, 13 Aug 2002 00:41:38 -0400,
>>><ABC@somewhere.net> wrote:
>>>
>>>>"John M. Williams" <jmwilliams@enforcergraphics.f2s.com>
>>>>wrote in
message
>>>>> Perhaps you mean tryptophan, which converts to
>>>>> serotonin, which has a substantial effect on both
>>>>> anxiety and depression. Unfortunately, federal laws
>>>>> prohibit the sale of tryptophan as a supplement.
>>>>
>>>No it is fortunate. Elevated serotonin causes anxiety.
>>>SSRIs do NOT increase serotonin.
>>
>>They inhibit post-synaptic reuptake of serotonin, thereby
>>increasing extracellular serotonin levels. That's why
>>they're called "selective serotonin reuptake inhibitors."
>>What didn't you understand about that?
>>
>Probably a lot more than you, I suspect.
The suspicions of an anonym are duly noted and granted the
respect they deserve.
>Yes, SSRIs inhibit serotonin re-uptake which initially
>increases the amount of that neurotransmitter both within
>synaptic gaps and in the extracellular fluid, but that isn't
>what produces the therapeutic effect. Thats is produced by a
>reduction in the density &/or sensitivity of receptors:
Yes, that it the primary target. It is not inconsistent with
what I said. And it does not establish that elevated serotonin
causes anxiety.
>The following is from a CME review article which
>unfortunately, is no longer on their site. The abstracts of
>the cited research do not mention the point Stern and Zohar
>are making, but you should be able to read the full papers at
>the library of any university with a psych department.
>
>>Clomipramine and selective serotonin reuptake inhibitors
>>(SSRIs) such as fluoxetine, fluvoxamine, paroxetine, and
>>sertraline have consistently been shown as effective
>>treatments for obsessive-compulsive disorder. It has
been
>>suggested that, though the initial effect of those agents is
>>an increase
of
>>serotonin concentration in the synaptic cleft, the final
>>effect, which
brings
>>about an improvement in obsessive-compulsive symptoms, is a
>>decrease in serotonin activity as adaptive downregulation of
>>5-HT receptors
occurs.9,10
>Stern L, Zohar J, Hendler T et al "The Potential Role of
>5-HT1D Receptors in the Pathophysiology and Treatment of
>Obsessive-Compulsive Disorder" CME reviews CNS1998_Stern.html
>
> (9) Hollander E, Fay M, Cohen B, Campeas R, et al. (1988)
> "Serotonergic and adrenergic sensitivity in
> obsessive-compulsive disorder: behavioral findings." Am
> J Psychiatry. vol 145:p 1015-17.
>
>(10) Zohar J, Insel TR, Zohar-Kadouch RC, et al 1998)
> "Serotonergic responsivity in obsessive-compulsive
> disorder: effects of chronic clomipramine treatment."
> Arch Gen Psychiatry. vol 45:p 167-172.
A single CME snippet which applies itself only to OCD and
uses the words "it has been suggested" is supposed to be
determinative about the nature of serotonergic tone? I
don't think so.
>See also:
>
>>All antidepressants are thought to act by causing
>>postsynaptic adaptive changes (e.g. in transducers or second
>>messengers) within these systems. Thus, the mechanism of
>>action of selective serotonin reuptake inhibitors (SSRIs)
>>cannot simply be explained in terms of inhibition of
>>serotonin (5-hydroxytryptamine) <5-HT> reuptake.
>>Fluvoxamine, sertraline and
fluoxetine
>>downregulate central beta-adrenoceptors, and all SSRIs are
>>believed to normalise central 5-HT1A- and 5-HT2-receptor
>>density and function in
patients
>>with depression.
>Leonard B E. (1992) "Pharmacological differences of serotonin
>reuptake inhibitors and possible clinical relevance." Drugs;
>vol 43 Suppl 2:p 3-9; discussion p 9-10. http://www.ncbi.nlm-
>.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&lis
t_uids=1378371&dopt=Abstract
Uh-huh. A "normalization" of specific serotonin receptors. Is
that supposed to be a surprise?
And, BTW, please note the comment on the downregulation of
beta-adrenoceptors ... isn't that completely consistent with
my original assertion that the use of tyrosine and its
conversions through the catecholamine cascade are NOT what one
wants for anxiety?
>However, the best guide that this is so is the effectiveness
>of the French antidepressant Tianeptine which is a Selective
>Serotonin Re-uptake Enhancer. That is it has the exact
>opposite mode of action to SSRIs, yet it is at least as
>effective as them http://www.ncbi.nlm.nih.gov:80/entrez/quer-
>y.fcgi?cmd=Retrieve&db=PubMed&lis
t_uids=10701468&dopt=Abstract
>
>When Tianeptine is taken with an SSRI they cancel each other
>out. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Re-
>trieve&db=PubMed&lis
t_uids=10683709&dopt=Abstract
And maybe it's effect has nothing to do with its enhancement
of 5-HT reuptake; maybe, like the article you just noted
states, it has to do with its actions upon the regulation of
dopamine and GABA receptors. This abstract would tend to agree
with that proposition:
Dziedzicka-Wasylewska M, Rogoz Z, Skuza G, Dlaboga D, Maj J.
Effect of repeated treatment with tianeptine and fluoxetine on
central dopamine D2 /D3 receptors. Behav Pharmacol 2002
Mar;13(2):127-38. http://www.ncbi.nlm.nih.gov/entrez/query.fc-
gi?cmd=Retrieve&db=PubMed&list_ui ds=11981225&dopt=Abstract
>And it is that initial increase in serotonin levels that
>often increases the anxiety levels of those starting on
>antidepressants
>
>But levels soon drop back to about baseline, perhaps even
>below as the brain reduces 5-HT synthesis in a bio-feedback
>response:
>
>[links to abstracts deleted]
And after wading through those abstracts, they all seem to
imply that the "bio-feedback" response is the result of
improved expression of 5-HT receptors, which is the purpose
for the increase in serotonin levels; that naturally includes
an improved expression of 5-HT autoreceptors which, in turn,
normalizes 5-HT production.
This still fails to establish that elevated 5-HT causes
anxiety.
>>Paroxetine (Paxil), one of the major SSRIs, is frequently
>>subscribed and FDA approved for anxiety disorder.
>>
>True. And most authorities recommend that anxiety patients be
>started on at most half the usual depressive dose because it,
>like most antidepressants and especially SSRIs trigger
>increased anxiety in the first few weeks. Even half doses is
>too high for many, with a quarter of the smallest tablet
>being better (except for extended/sustained release ADs as
>these should not be cut under any circumstance).
>
>>Please state your references as to the contrary proposition.
>
>Done above.
>
>The bottom line is that Tryptophan cannot do what
>antidepressants do.
Probably not to the same extent, and that would be true for a
number of reasons, including the fact that it requires
conversion. That still does not establish that elevated
serotonin levels cause anxiety.
>And it is probably impossible to buy uncontaminated
>Tryptophan and 5-HTP.
My understanding was that the initial contaminations leading
to the ban were anecdotal.
--
John M. Williams jmwilliams@enforcergraphics.f2s.com