Antidepressants Alter
Rat Brain Cells In
Only Four Days
From Ian Goddard <>
From Brasscheck <>
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
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 in animals.
``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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