Long term anti depressant treatment: danger?

John H. johnh at faraway.xxx
Thu Mar 20 04:52:21 EST 2003


Thanks Ian, I forgot about that thalamus reference you raised. This is
interesting because raphe nuclei cells project to the pvn and have
significant effects of GC receptor numbers in the hippocampus. (all very
confusing, I have no hope at present of delineating all this) I'm very
cynical re current paradigm for understanding depression, the whole thing is
skewed towards serotonin but in the picture I'm trying to create there is
strong HPA and immunological component to depression. It is a failure of
systemic homeostasis. Often find increased cortisol, increased il12 and\or
il6, altered cognitive functions.

Ken has a point regarding this "short circuiting" strategy because serotonin
depletion is the end result of a series of processes. It is, at this point,
v. difficult to determine how serotonin depletion can arise but the best
bets are via immune mediated IDO tryptophan depletion, brain il 1 being
chronically present under stress, and increased NO leading to oxidative
pressures and depleting tyrosine and\or tryptophan hydrox activity.

Sadly, I noted last night that in the past tryptophan supplementation had
proved effective, perhaps as much as SSRI's, in treating depression. In the
80's there was a number of poisonings from taking the t supps and it was
removed from the shelves. It was later found that this occurred because of a
bad batch being made by a Japanese manufacturer. In spite of this, the ban
remains, leaving the pharmaceuticals to peddle their expensive wares ... .

Given the poor response rates to ssri's and the abundant research indicating
different approaches to treating depression, we still seem stuck on the
serotonin thing. We've got the wrong end of the stick.


John H.


"Ian Goddard" <igoddard at erols.mom> wrote in message
news:rnth7vgmgb765p4ievc6k1r57rnn1a1m08 at 4ax.com...
> On Wed, 19 Mar 2003, "John H." <johnh at faraway.xxx> wrote:
>
> >New one on me, comments anyone?
>
>
>http://www.alphagalileo.org/index.cfm?fuseaction=readRelease&Releaseid=1295
9
> >Can Long-term Treatment With Antidepressant Drugs Worsen The Course Of
> >Depression?  For further information, please contact:
>
>
>   IAN: Interesting. A few possibly relevant comments: in raising
>   serotonin (5HT) levels, antidepressants cause a downregulation
>   (ie, a reduction) of 5HT receptors. A plausible hypothesis might
>   be that over time, downregulation might counteract any uplifting
>   effect of an antidepressant-induced 5HT increase. The brain tries
>   to maintain its natural state, and downregulation should tend to
>   diminish the artificially increased 5HT signal. Consider that
>   FDA approval is usually based on human studies that examine use
>   over only a few months. Cocaine could likely pass FDA approval
>   as an antidepressant based on such short-term efficacy standards.
>   However, as Freud found out, short- and long-term effects differ!
>
>   Consider also the post I made a few months ago citing studies that
>   found the SSRI Paxil (paroxetine) causes atrophy of the thalamus,
>   which is in a region (HPA axis) where a lot of the downregulation
>   occurs. I might be wrong, but it seems to me that common sense
>   would tend to suggest that long-term exposure to any substance
>   that causes atrophy of a brain region might have negative results.
>
> http://groups.google.com/groups?selm=3d64dfd6.218276288%40news.erols.com
>
>   OBE Explanation? See: http://iangoddard.net/paranorm.htm
>
>
>
> >Giovanni Andrea Fava
> >Editor Psychotherapy and Psychosomatics
> >fava at psibo.unibo.it
> >390512091339
> >   17 March 2003
> >
> >
> >
> >
> >keywords
> >Medical, Health, Psychology
> >
> >
> >
> >   The Journal of Clinical Psychiatry releases a review by Giovanni A.
Fava
> >(University of Bologna) which is likely to stir a lot controversy and be
> >disliked by the Big Pharma.
> >The possibility that antidepressant drugs, while effectively treating
> >depression, may worsen its course has received inadequate attention.
> >
> >A review of the literature, suggesting potential depressogenic effects of
> >long-term treatment with antidepressant drugs was performed. A Medline
> >search was conducted using the key-words tolerance, sensitization,
> >antidepressive agents, and switching. This was supplemented by a manual
> >search of Index Medicus under the heading "antidepressant agents" and a
> >manual search of the literature for articles pointing to paradoxical
effects
> >of antidepressants.
> >
> >A number of reported clinical findings point to the following
possibilities:
> >very unfavorable long-term outcome of major depression treated by
> >pharmacological means; paradoxical (depression-inducing) effects of
> >antidepressant drugs in some patients with mood and anxiety disturbances;
> >antidepressant-induced switching and cycle acceleration in bipolar
disorder;
> >occurrence of tolerance to the effects of antidepressants during
long-term
> >treatment; onset of resistance upon re-challenge with the same
> >antidepressant drug in a few patients; and withdrawal syndromes following
> >discontinuation of mood-elevating drugs. These phenomena in susceptible
> >individuals may be explained on the basis of the oppositional model of
> >tolerance. Continued drug treatment may recruit processes that oppose the
> >initial acute effects of a drug and may result in loss of clinical
effect.
> >When drug treatment ends, these processes may operate unopposed, at least
> >for some time, and increase vulnerability to relapse. This hypothesis
needs
> >to be tested, even though its scientific exploration is likely to
encounter
> >considerable methodological and ideological difficulties. The clinical
> >implications of this hypothesis in depression are considerable.
> >Antidepressant drugs are crucial in the treatment of major depressive
> >episodes. However, appraisal of paradoxical effects that may occur in
> >susceptible patients during long-term treatment may lead to a more
effective
> >use of the drugs.
> >
> >
> >
>





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