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=12959>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.
OBE Explanation? See: http://iangoddard.net/paranorm.htm
>Giovanni Andrea Fava
>Editor Psychotherapy and Psychosomatics
>fava at psibo.unibo.it>390512091339
> 17 March 2003
>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
>>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.