- I became aware of the dangers of antidepressants after
Littleton gunkid Eric Harris was found to have been on the antidepressant
Luvox, prompting me to research the topic. I then realized there was probably
a good reason why the last words my Mother spoke as the cogent person she
was before her sudden decline into dementia were descriptions of the aesthetic
qualities of hallucinations that Prozac was causing. Her doctors dismiss
any possibility of a link between her dementia and Prozac, yet she had
a range of neurotoxic reactions to Prozac and her records show that the
onset of her sudden decline was the SAME month that she started taking
Prozac! In a matter of months she went from having a 99-percentile IQ to
not being sure if people on TV can see you. I wonder if the following study
may be shedding light on what Prozac apparently did to my Mother. The study
found that large doses of SSRIs such as Prozac caused some rat brain cells
to "shrivel up" in four days! (First is a media review followed
by the study abstract): _____
- Antidepressants Found to Alter Brain Cells in
- By Mitch Rustad c.2000
- Medical PressCorps News Service
- A study conducted in animals raises concerns about the
prolonged use of such commonly prescribed antidepressant drugs as fluoxetine
(Prozac, Lilly) and sertraline (Zoloft, Pfizer).
- Researchers found changes in brain cells of rats treated
with large doses of two antidepressants and two anti-obesity drugs. In
some cases, the cells shriveled up or took on abnormal corkscrew shapes.
- The study led by Dr. Madhu Kalia, professor of biochemistry,
molecular pharmacology, anesthesiology and neurosurgery at Jefferson Medical
College of Thomas Jefferson University in Philadelphia, compared the effects
of four days of high doses of four drugs: fluoxetine, sertraline, sibutramine
(Meridia, Knoll) and dexfenfluramine (Redux), on rat brain cells. Each
rat received only one drug. The study said that while clinical significance
of the findings isn't known, there is a need for similar studies of other
classes of drugs that act on the central nervous system.
- After the toxic doses of drugs were halted, and the animals'
brains subsequently examined, the researchers saw marked changes in some
nerve terminals that release the neurotransmitter serotonin.
- ``If any patient who's on any of these drugs, takes the
drug in high enough doses for long periods of time, there could be some
changes occurring in the brain,'' said Kalia. ``There is the potential
that this could be happening. This study in animals is a red flag that
perhaps we shouldn't use these drugs with reckless abandon.''
- These drugs, known collectively as selective serotonin
reuptake inhibitors (SSRIs), increase the level of serotonin, which is
vital to brain cell communication. Low serotonin levels are linked to mood
and eating disorders.
- What do these findings mean? ``We don't know if results
with four days of drug treatment are clinically significant,'' said Kalia.
``We don't know if the cells are dying. That's the key question. We need
to do more studies to prove cell death. These effects may be transient
and reversible. Or they may be permanent.'' The study is published in the
March 6 issue of Brain Research.
- Serotonin is ubiquitous in the central nervous system,
making it a frequent target for medications. Drugs such as fluoxetine and
sertraline raise serotonin levels to treat depression and panic attacks.
Another class of SSRIs, anti-anorexics used for weight loss, includes sibutramine
and dexfenfluramine (withdrawn from the market in 1997 after being linked
to heart-valve problems). Such drugs block circulating serotonin. After
brain cells use serotonin, it is recycled in the brain. SSRIs keep serotonin
from being recirculated back to the brain for subsequent use, allowing
the chemical to stay active in the brain.
- More than a decade ago, rat studies showed that high
doses of dexfenfluramine could change the shape of some brain terminals,
said Kalia. Some researchers attributed the effect to the fact that the
drug was also a serotonin releaser.
- ``It was a big mystery why with high doses these brain
terminals looked like corkscrews,'' said Kalia. ``We asked the question,
'Would other SSRIs cause the same effects in high doses?'''
- With some patients using some of these drugs for long
periods of time, and with scientists unsure of the long-term effects of
many of these drugs, Kalia and her colleagues plan to do long-term studies
- ``We will lower the doses to about 10 to 30 times the
therapeutic dose and give it to the rats for six months to a year,'' said
Kalia. ``We will examine the rats at selected time periods to see if these
changes occur in serotonin cells over the long term, or if the brain adjusts,''
she continued. The researchers would then look for behavioral and neurological
effects of any brain changes.
- ``We need to find out if these changes are effecting
behavioral changes in the rat and in patients,'' said Kalia. ----
- Brain Research (2000;16251)
- ABSTRACT TO THE STUDY CITED
- IN THE MEDIA REPORT ABOVE
- Brain Research, 2000 Mar 6;858(1):92-105
- Comparative study of fluoxetine, sibutramine, sertraline
and dexfenfluramine on the morphology of serotonergic nerve terminals using
- Kalia M, O'Callaghan JP, Miller DB, Kramer M
- Department of Biochemistry, Molecular Pharmacology and
Anesthesiology, Jefferson Medical College, Thomas Jefferson University,
233 South 10th Street, Suite 309, Philadelphia, PA, USA
- [Record supplied by publisher]
- We compared the effects of treatment with high doses
of fluoxetine, sibutramine, sertraline, and dexfenfluramine for 4 days
on brain serotonergic nerve terminals in rats. Methylenedioxymethamphetamine
(MDMA) and 5,7-dihydroxytryptamine (5,7-DHT) were used as positive controls
because both compounds deplete brain serotonin. Food intake and body weight
changes were also monitored and yoked, pair-fed animals were used to control
for possible changes in morphology due to nutritional deficits. Fluoxetine,
sibutramine, sertraline and dexfenfluramine all produced a significant
reduction in body weight. Fluoxetine, sibutramine and sertraline treatment
resulted in no depletion of brain serotonin but produced morphological
abnormalities in the serotonergic immunoreactive nerve network. In contrast,
dexfenfluramine and MDMA depleted brain serotonin and produced morphological
changes in the serotonin nerve network. These results indicate that even
though fluoxetine, sibutramine and sertraline do not deplete brain serotonin,
they do produce morphological changes in several brain regions (as identified
by serotonin immunohistochemistry). Dexfenfluramine and MDMA, on the other
hand, markedly deplete brain serotonin and also produce morphological changes.
Collectively, these results lend support to the concept that all compounds
acting on brain serotonin systems, whether capable of producing serotonin
depletion or not, could produce similar effects on the morphology of cerebral
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