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Depression: Serotonin imbalance?

It may be that your doctor has told you that you are depressed as a result of a
chemical imbalance in your brain, perhaps low serotonin. You may also have been
told that antidepressants correct this imbalance. These ideas may be attractive
(and seductive), but there's no compelling evidence to support either of them.

Serotonin is sometimes termed the "happy chemical" and although "serotonin
does, unquestionably, play an important role in mood" (as 'Neuroskeptic' writes
here) this is quite different from claiming that low serotonin directly causes people
to feel depressed.

It is true that some physical conditions can lead to depression, as do quite a few
medications [see in this web here], but this is different from the assertion that
depression is caused by chemical imbalances in the brain. If we are depressed,
we are invariably depressed about something or someone: life, people, worries,
fears, ill-treatment, injustice, memories, poverty, a sense of hopelessness - the
possibilities are endless.

Serotonin pathways in the brain

The whole idea of antidepressants
supposedly correcting chemical
imbalances has more to do with drug
company marketing than evidence-
based science. It was around 1960
that the theory for low serotonin and
depression emerged from studies by
George Ashcroft and colleagues at
Edinburgh University. Within ten
years he was clear that the theory
was unsupported scientifically and
openly said so. 

Some years later the drug
companies resurrected this dead
theory to help promote anti-
depressant drugs – suggesting,
without any adequate scientific
basis, that these drugs correct low
levels of serotonin as a way of
relieving depression. This was
simply a "triumph of marketing
over science."4

Interfering with serotonin levels has repercussions right across the brain (see
image above) and affects dopamine transmission too. Both these neuro-
transmitters have extensive networks across the brain reaching “into nearly
every corner and crevice of the brain and down the spinal cord”.1 Thus
movement, memory, thinking, emotions, sexual activity and more are adversely
affected; surely, these don’t sound like the sort of changes we want unless
absolutely necessary. 

...to propose that researchers can objectively identify a
“chemical imbalance” at the molecular level is not
compatible with the extant science. In fact, there is no
scientifically established ideal “chemical balance” of
serotonin, let alone an identifiable pathological imbalance.
To equate the impressive recent achievements of
neuroscience with support for the serotonin hypothesis
is a mistake. Prof J. Leo & J. Lacasse 6
  Although it is often stated
with great confidence that
depressed people have
a serotonin or
norepinephrine deficiency,
the evidence actually
contradicts these claims
Prof Elliot Valenstein
    no abnormality
of serotonin in
depression has
ever been
    Prof David Healy
Psychiatrist and Psychopharmacologist
No psychiatric disorder
has been conclusively
linked to a single
biochemical disturbance…
As far as depression is
concerned studies of
serotonin and noradrenalin
function show a confusing
and conflicting picture...
Expert psychiatrists and
researchers admit that no
one has yet demonstrated
that there is an abnormality
of serotonin in depression
Dr Joanna Moncrieff
Academic psychiatrist, UCL
In truth, the “chemical
imbalance” notion was
always a kind of urban
legend - never a theory
seriously propounded by
well-informed psychiatrists

The concept of the Serotonin Selective Reuptake Inhibitor (SSRI) - including
well known brands such as Prozac and Seroxat - was an astute marketing ploy.
For the general public the use of the word “selective” carries the idea of
something specific – rather like a drug equivalent of keyhole surgery – precisely
targeting and correcting the problem. As we have seen, this is far from true as
these drugs have a global impact upon the brain and the rest of the body. In
truth, "[c]orporate profits are dependent on the illusion that drugs work through
highly specific pathways”2; but, our healthcare should not be entrusted to an

Worryingly, antidepressants actually change the structure and workings of the
brain. "Long-term treatment with an SSRI causes some serotonin receptors to
desensitize and fail to respond anymore, while others simply become less
sensitive to stimulation by serotonin. In addition, nerve cells in individuals
treated with an SSRI may make less serotonin 7." This is the conclusion of
Professor Michael Gershon who has studied serotonin for over 30 years. In
this way, antidepressants seem to be creating and not correcting a chemical

Dr Joanna Moncrieff and Professor David Cohen raise an important question:
“Do antidepressants cure or create abnormal brain states?" You can read the
article here.

And so ...

  • Assuming depression to be caused by chemical imbalances in the brain
    means trust is primarily placed in a medical understanding (mis-
    understanding?) of depression. This is one perspective, and weakly
    supported in science. And yet, in reality, depression seems invariably to
    occur within the context and circumstances of our lives. (More about this
    in this website here).
  • Whether or not to take antidepressant drugs is a choice. To make this
    choice we need accurate information on what they do - their
    effectiveness and adverse effects too. More about antidepressants in
    this website here, and for children here.
  • Unfortunately, drug companies are known to exaggerate the benefits of
    their products and to play down the risks; in fact, as Leemon McHenry
    points out “the vast organization and powerful lobby of pharmaceutical
    marketing is currently winning against scientific accuracy.”3 (More
    about this in this website here).
  • “Over 90% of the serotonin in the body is in the gut or cardiovascular
    system – which means that drugs acting on serotonin reuptake are likely
    to have potent effects throughout the body – impairing sexual function,
    remodeling bones, making hemorrhages more likely.”5
  • Maybe doubt concerning the integrity of the biochemical hypotheses for
    so-called mental illnesses may spur us to greater trust in ourselves and
    those we know we can trust.
Prof Ronald Pies
Editor of Psychiatric Times
Maybe doubt concerning
the integrity of the
biochemical hypotheses
may spur us to greater
trust in ourselves and
in those we know
we can trust
  Mick Bramham,
Existential Psychotherapist

We [psychiatrists] have
no clear evidence that
chemical imbalances are
at the root of any mental
we give patients elaborate
explanations of how the
drugs work chemically.
It makes us feel more
scientific, and gives
patients a feeling of
confidence in us, but it's
little more than made up

    Dr Daniel Carlat

References - Bibliography - Further reading

1 Breggin, P & Breggin, G. (1994) Talking Back to Prozac. New York: St Martin's Press

2 Bracken, P. & Thomas, P. (2005) Postpsychiatry: Mental Health in a Postmodern World. UK: Oxford University Press

3 McHenry, L. Biomedical Research & Corporate Interests: A question of academic freedom.
Mens Sana Monogr. Jan - Dec 2008, p146-156. Full study.

4 Antonuccio, D.O. et al. Antidepressants: A triumph of marketing over science. Prevention &
, Vol 5, Article 25 2002. Full study.

5 Healy, D et al. Data Based Medicine Position Paper: Antidepressants for Takers. PDF
available from RxISK

6 Leo, J. & Lacasse, J. (2005) Serotonin and Depression: A Disconnect between the
Advertisements and the Scientific Literature. PLoS Med 2(12): e392. Full essay here.

7 Gershon, M. (1998) The Second Brain. New York: HarperCollins Publishers


Carlat, D. (2010) Unhinged: The Trouble with Psychiatry - A Doctor's Revelations about a Profession in Crisis. New York: The Free Press.

Healy D. (2004) Let Them Eat Prozac. New York & London: New York University Press.

Moncrieff, J. & Cohen, D. 2006 Do Antidepressants Cure or Create Abnormal Brain States?
PLoS Medicine Vol 3 Issue 7 July 2006. Full study.

Valenstein, E.S. (1998) Blaming the Brain: The Truth About Drugs and Mental Health. New York:
The Free Press.