Prozac: Brain Damage Risk?

From: Ian Goddard (
Date: Wed Mar 08 2000 - 23:31:48 MST

 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 Rats

   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 in

         ``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)



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 serotonin immunohistochemistry.

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
serotonin systems.

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   "There are times when you cannot keep your job and
  put alternative explanations for data on the table."
   Former FBI Special Agent Dr. Frederic Whitehurst


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