Do Antidepressants Permanently Rewire the Human Brain?
Please see "Definitions" at the end of this article. Words defined are indicated by an asterisk (*) after the word.
Source: The Serotonin Surprise, by Gary Greenberg.
'I think you have to accept that there's a structural change in your brain when you take drugs like Prozac'
to argue. We argue about treatment theories, about our clients and their
families, about the office coffeepot. And during the past decade we have tended
to fixate, as we say in the business, on the subject of Prozac.
It used to be fairly
easy to agree about commonly prescribed psychiatric drugs such as Valium: They anesthetized people, covered up
problems, illegitimately took the place of therapy. But Prozac and the other
antidepressants that work by enhancing serotonin* activity in the brain
have eluded such easy criticism.
would find that our clients who took them felt more alive, more resilient, more able to engage in the honest self-reflection necessary
to therapy. And we could not help but agree with Peter Kramer, who wrote in
Listening to Prozac that the drug can remake the self - which was supposed
to be our job.
haven't been alone in their Prozac anxiety. Americans have always been
ambivalent about mind-altering drugs, and many wonder if it is a good thing
that today some 30 million Americans -- many of them not clinically depressed
but rather among the "worried well" -- have taken serotonin enhancers
at one time or another.
issues are more troubling, like the serious side effects -- which
include violent impulses, agitation, and sexual dysfunction -- that have been
reported since the drugs first appeared and have never been fully confirmed or
perhaps most disconcerting is the fact that 15 years after the first of the
serotonin enhancers -- Prozac -- was put on the market, the precise reason
why they relieve depression remains unknown.
scientists, however, think they are on the verge of solving this mystery,
suggesting that serotonin enhancers may work by encouraging the growth of new
At the same time, other researchers have found that high doses of
these drugs cause changes in neurons* that some would call brain damage -- a
finding that may have some bearing on the range of reported side effects.
sets of research point to the possibility that serotonin enhancers alter brains
in ways researchers never imagined.
also known as 5-hydroxytryptamine (5-HT), was first isolated in 1933, when it
was discovered in the gut and called enteramine. In
1947 it was found in blood platelets, and the molecule earned its current name,
serotonin, when it also proved to constrict blood vessels. Soon after,
serotonin was identified in the brain. But its role was unknown until some drug
tests in the 1950s drew unexpected results.
In 1975 a
group at Eli Lilly quietly reported that they had synthesized 110140, a
substance that targeted serotonin with precision. Eleven years later, 110140
became Prozac, one of the most successful drugs ever brought to market,
responsible in 1999 for 26 percent of the revenues of one of the largest
companies in the United States.
like Prozac work by interfering with the metabolism of the brain.
travels from one neuron to another by crossing a gap known as a synapse.
Normally, once the receiving neuron is activated, the chemical is reabsorbed by
the brain. But Prozac prevents this re-absorption, allowing serotonin to remain
in the synapse and interact with its targets for much longer than it otherwise
crucial question remains: We simply
don't know why having a synaptic lake brimming with serotonin makes people
While there is evidence that some depressed people have lower
levels of serotonin breakdown products in their spinal fluid and different
brain anatomies from the overall population, the proof of the commonly held notion
that a deficiency or imbalance in the serotonin system causes depression
Nor is it
known why the drugs generally take three to six weeks to alter mood, why they
help people with non-depression-related problems like shyness or compulsiveness,
why people who were not depressed in the first place sometimes feel
"better than well," or why the drugs sometimes lose their efficacy
over the long term.
gaps in our knowledge, the post-Prozac era has seen the rise of a singular
idea, one that can be called mythic for both its explanatory power and its lack
of evidence -- depression is best understood and treated as a biochemical
aberration for which drugs like Prozac are the silver bullets.
monkeys routinely grow new brain cells, a process known as neurogenesis.
There is an emerging body of evidence that people, too, undergo neurogenesis throughout their lives. The discovery is
provocative because neurogenesis seems most prevalent
in the hippocampus -- a region of the brain associated with learning, memory,
and, perhaps, emotion.
have found that stress can often trigger depression. And stress floods
the brain with certain hormones (glucocorticoids)
that are known to suppress neurogenesis or even kill
neurons, especially in an area of the hippocampus known as the dentate gyrus.
have found that depressed patients have somewhat smaller hippocampi
than non-depressed people. Moreover, patients with diseases like Cushing's
syndrome and temporal lobe epilepsy that cause cell loss in the hippocampus
have a much higher risk of depression than the rest of the population.
takes about three to six weeks for new cells to mature -- the same time it
takes serotonin-enhancing drugs to make a difference in a patient. Add all this
evidence up and you have, the leading candidate" for understanding what
happens in the brains of depressed people and why drugs like Prozac help them.
people get depressed when chronic or acute stress brings about "the death
of neurons or the failure to grow new neurons. People dwell on negative things
and are incapable of forming new cognition about the future being positive and
things getting better -- until they have the ability to grow new neurons that
mediate this new cognition.
While nobody knows for sure what these new cells do
in humans, a recent study in rats found the newborn neurons were crucial for
forming certain kinds of memories.
to accept that there is a structural change in your brain when you take drugs
like Prozac. If people aren't comfortable with that, that's something else to
psychiatrist Joseph Glenmullen finds such
brain-altering effects more unsettling than intriguing. Last year he published
Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil,
and Other Antidepressants with Safe, Effective Alternatives, a
book that details his brief against the drugs.
far more serious and common side effects than their manufacturers report. The
Food and Drug Administration has failed to sufficiently investigate these
reports; patients' complaints about the drugs are largely ignored; and the
drugs are prescribed too often and for far too broad a range of distress.
most important, Glenmullen believes the way the
drugs are marketed suggests that depression is primarily a biological
problem to be solved by biochemical means, instead of a complex biopsychosocial phenomenon that can be resolved in many
cases with traditional psychotherapies and without drugs.
who does prescribe serotonin enhancers when he deems it appropriate, likens
them to such stimulants as amphetamines and cocaine -- drugs that were once
used widely, without fear of side effects, to give people more energy, improved
mood, and increased focus.
has long suspected that drugs that alter serotonin metabolism cause profound
changes in the brain. He bases his suspicion on a body of research during the
last 20 years by scientists investigating another class of drugs that includes
MDMA (Ecstasy) as well as fenfluramine, the diet drug
recently removed from the market because of its association with heart valve
drugs do more than just block serotonin reuptake; they primarily stimulate the
release of large quantities of serotonin from nerve endings into the brain. The
resulting flood is thought to cause the mind-altering effects of MDMA. And that
flood, some scientists argue, leaves brain damage in its wake.
monkeys and rats are given high doses of serotonin releasers -- up to 40 times
the dose that people generally take -- the microscopic architecture of their
brains looks different from normal brains.
The nerve fibers
(axons) that carry serotonin to the target cells seem to change their shape and
diminish in number -- effects some scientists claim are properly understood as
brain damage. Glenmullen
is convinced these results raise questions about other serotonergic
drugs like Prozac, and a recent study has only increased his concern.
conducted by neurologist Madhu Kalia
at Jefferson Medical College in Philadelphia and scientists at the Centers for
Disease Control and Prevention showed that the rats given very high doses (up
to 100 times the human dose, by body weight) of Prozac and Zoloft contained the
same kinds of brain abnormalities -- neurons with swollen or kinked tips -- as
rats who were given high doses of serotonin releasers.
O'Callaghan, a Centers for Disease Control
neuroscientist and a coauthor of the study, doesn't think the results indicate
that Prozac causes brain damage. To the contrary, he and his team believe that
neither serotonin enhancers nor serotonin releasers are properly understood as neurotoxic.
to O'Callaghan, the point of the study was to show that even a drug like
Prozac, which virtually no one claims is neurotoxic,
can produce some of the same abnormalities as the serotonin releasers.
Other scientists, in his view, have been too quick to "deduce what they
think is going on in the [nerve] fibers" from
two pieces of data.
serotonin releasers deplete serotonin, and the microphotographs of brains
exposed to high doses of these drugs look abnormal. O'Callaghan believes that
scientists should rethink their definition of neurotoxicity,
because high doses of Prozac and Zoloft, which do not deplete serotonin, cause
the same transient abnormalities as do high doses of drugs such as MDMA.
drugs are much more carefully scrutinized for potential harmful effects than
pharmaceutical drugs, which are studied for their relative risks and benefits
rather than for all imaginable dangers.
addition, toxic effects that are observed only at high dosages in short-term
tests may also occur over long periods of time at much lower dosages. But once
a drug is approved, a critical opportunity for turning up evidence during
testing has been lost. Moreover, the manufacturer gains a strong interest
in controlling what consumers know about drugs.
In Glenmullen's view, regulatory agencies don't always do
enough to help consumers either. He devoted a chapter in his book to the FDA's decision to allow Lilly not to include a warning with
Prozac that the drug can cause or worsen suicidal symptoms -- despite studies
that indicated that up to 3.5 percent of patients might experience such
advertising campaigns by the drug companies, he says, and you have a social
climate in which "everyone wants a serotonin booster" and everyone
believes in a "pharmacological fantasy" that we can use mood-altering
drugs for a variety of ills without giving serious thought to the potential
offers a different Rx: fewer drugs and more therapy. He believes many people
taking serotonin-enhancing drugs would respond as well to talk therapy. And
talk isn't the only option. Aerobic exercise, such as jogging or dance, also
combats less severe cases of depression. Studies in rats suggest that exercise
boosts serotonin and neurogenesis as well.
the use of any drug, especially one that tinkers with the brain's machinery,
involves risk, the full extent of which can't be known until a large number of
people have used it for many years.
familiar caution may take on a new urgency when we realize that research about
serotonin enhancers still offers more questions than answers.
Dr. Mercola's Comment:
irony here is that probably over 95% of the antidepressant drugs are not
needed. Does that mean one should use herbal alternatives like St. John's wort?
Absolutely not, as any type of pill is only a "band aid" solution for
choices are clearly an important part of the treatment. However, one will
nearly always need to address emotional wounding if one is to reverse this
illness at its foundational root.
Serotonin - a
chemical substance (produced in the body) that transmits nerve impulses across
a synapse (a region where nerve impulses are transmitted and received), derived
from tryptophan (an essential amino acid, released
from proteins by digestion and a precursor of serotonin), that is involved in
sleep, depression, memory, and other neurological processes. Note:
Humans cannot manufacture essential amino acids,
therefore they must be obtained from foods.
ProzacTrademark - a brand of fluoxetine
Neurons(also called nerve cell)
- a specialized, impulse-conducting cell that is the functional unit of the