Posted on:
Sunday, January 4th 2015 at 4:45 am
Written By:
Millions believe
depression is caused by 'serotonin deficiency,' but where is the science in
support of this theory?
"Depression is a serious medical condition that may be due
to a chemical imbalance, and Zoloft works to correct this imbalance."
Herein lies the serotonin myth.
As one of only two countries in the world that permits direct to
consumer advertising, you have undoubtedly been subjected to promotion of the
"cause of depression." A cause that is not your fault, but rather; a
matter of too few little bubbles passing between the hubs in your brain! Don't
add that to your list of worries, though, because there is a convenient
solution awaiting you at your doctor's office...
What if I told you that, in 6 decades of research, the serotonin
(or norepinephrine, or dopamine) theory of depression and anxiety has not
achieved scientific credibility?
You'd want some supporting arguments for this shocking claim.
So, here you go:
The Science of Psychiatry
is Myth
Rather than some embarrassingly reductionist,
one-deficiency-one-illness-one-pill model of mental illness, contemporary
exploration of human behavior has demonstrated that we may know less than we
ever thought we did. And that what we do know about root causes of mental
illness seems to have more to do with the concept of evolutionary
mismatch than with genes and chemical deficiencies.
In fact, a meta-analysis of over 14,000 patients
and Dr. Insel, head of the NIMH, had this to say:
"Despite high expectations, neither genomics nor imaging
has yet impacted the diagnosis or treatment of the 45 million Americans with
serious or moderate mental illness each year."
To understand what imbalance is, we must know
what balance looks like, and neuroscience, to date, has not
characterized the optimal brain state, nor how to even assess for it.
A New England Journal of Medicine review on Major
Depression, stated:
" ... numerous studies of norepinephrine and serotonin
metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem
studies of the brains of patients with depression, have yet to identify the
purported deficiency reliably."
The data has poked holes in the theory and even the field of
psychiatry itself is putting down its sword. One of my favorite essays
by Lacasse and Leo has compiled sentiments from influential thinkers in the
field – mind you, these are conventional clinicians and researchers in
mainstream practice – who have broken rank, casting doubt on the entirety of
what psychiatry has to offer around antidepressants:
Humble Origins of a
Powerful Meme
In the 1950s, reserpine, initially introduced to the US market
as an anti-seizure medication, was noted to deplete brain serotonin stores in
subjects, with resultant lethargy and sedation. These observations colluded
with the clinical note that an anti-tuberculosis medication, iproniazid,
invoked mood changes after five months of treatment in 70% of a 17 patient
cohort. Finally, Dr. Joseph Schildkraut threw fairy dust on these mumbles and
grumbles in 1965 with his hypothetical manifesto entitled "The
Catecholamine Hypothesis of Affective Disorders" stating:
"At best, drug-induced affective disturbances can only be
considered models of the natural disorders, while it remains to be demonstrated
that the behavioral changes produced by these drugs have any relation to
naturally occurring biochemical abnormalities which might be associated with
the illness."
Contextualized by the ripeness of a field struggling to
establish biomedical legitimacy (beyond the therapeutic lobotomy!), psychiatry
was ready for a rebranding, and the pharmaceutical industry was all too happy
to partner in the effort.
Of course, the risk inherent in "working backwards" in
this way (noting effects and presuming mechanisms) is that we tell ourselves
that we have learned something about the body, when in fact, all we have
learned is that patented synthesized chemicals have effects on our behavior.
This is referred to as the drug-based model by Dr.
Joanna Moncrieff. In this model, we acknowledge that antidepressants have
effects, but that these effects in no way are curative or reparative.
The most applicable analogy is that of the woman with social
phobia who finds that drinking two cocktails eases her symptoms. One could
imagine how, in a 6 week randomized trial, this "treatment" could be
found efficacious and recommended for daily use and even prevention of
symptoms. How her withdrawal symptoms after 10 years of daily compliance could
lead those around her to believe that she "needed" the alcohol to
correct an imbalance. This analogy is all too close to the truth.
Running With Broken Legs
Psychiatrist Dr. Daniel Carlat has said:
"And where there is a scientific vacuum, drug companies are
happy to insert a marketing message and call it science. As a result,
psychiatry has become a proving ground for outrageous manipulations of science
in the service of profit."
So, what happens when we let drug companies tell doctors what
science is? We have an industry and a profession working together to maintain a
house of cards theory in the face of contradictory evidence.
We have a global situation in which increases
in prescribing are resulting in increases in severity of illness (including
numbers and length of episodes) relative to those who have never been treated
with medication.
To truly appreciate the breadth of evidence that states
antidepressants are ineffective and unsafe, we have to get behind the walls
that the pharmaceutical companies erect. We have to unearth unpublished data,
data that they were hoping to keep in the dusty catacombs.
A now famous 2008 study in the New
England Journal of Medicine by Turner et al sought to expose the
extent of this data manipulation. They demonstrated that, from 1987 to 2004, 12
antidepressants were approved based on 74 studies. Thirty-eight were positive,
and 37 of thesewere published. Thirty-six were negative
(showing no benefit), and 3 of these were published as such
while 11 were published with a positive spin (always read the
data not the author's conclusion!), and 22 were unpublished.
In 1998 tour de force, Dr. Irving Kirsch, an expert on the
placebo effect, published a meta-analysis of 3,000 patients who
were treated with antidepressants, psychotherapy, placebo, or no treatment and
found that only 27% of the therapeutic response was attributable to the drug's
action.
This was followed up by a 2008 review, which invoked the
Freedom of Information Act to obtain access to unpublished studies, finding
that, when these were included, antidepressants outperformed placebo in only 20
of 46 trials (less than half!), and that the overall difference between drugs
and placebos was 1.7 points on the 52 point Hamilton Scale. This small
increment is clinically insignificant, and likely accounted for by medication
side effects strategically employed (sedation or activation).
When active placebos were used, the Cochrane database found that
differences between drugs and placebos disappeared, given credence to the
assertion that inert placebos inflate perceived drug effects.
The finding of tremendous placebo effect in the treatment groups
was also echoed in two different meta-analyses by Khan et al who
found a 10% difference between placebo and antidepressant efficacy, and
comparable suicide rates. The most recent
trial examining the role of
"expectancy" or belief in antidepressant effect, found that patients
lost their perceived benefit if they believed that they might be getting a
sugar pill even if they were continued on their formerly effective treatment
dose of Prozac.
The largest, non-industry funded study, costing the public $35
million dollars, followed 4000 patients treated with Celexa (not blinded, so
they knew what they were getting), and found that half of them improved at 8
weeks. Those that didn't were switched to Wellbutrin, Effexor, or Zoloft OR
"augmented" with Buspar or Wellbutrin.
Guess what? It didn't matter what was done, because they
remitted at the same unimpressive rate of 18-30% regardless with only 3% of
patients in remission at 12 months.
How could it be that medications like Wellbutrin, which purportedly
primarily disrupt dopamine signaling, and medications like Stablon which
theoretically enhances the reuptake of serotonin, both work to resolve this
underlying imbalance? Why would thyroid, benzodiazepines, beta blockers, and
opiates also "work"? And what does depression have in common with
panic disorder, phobias, OCD, eating disorders, and social anxiety that all of
these diagnoses would warrant the same exact chemical fix?
Alternative options
As a holistic clinician, one
of my bigger pet peeves is the use of amino acids and other nutraceuticals
with "serotonin-boosting" claims. These integrative
practitioners have taken a page from the allopathic playbook and are seeking to
copy-cat what they perceive antidepressants to be doing.
The foundational
"data" for the modern serotonin theory of mood utilizes tryptophan
depletion methods which involve feeding volunteers amino acid mixtures without
tryptophan and are rife with complicated interpretations.
Simply put, there has never
been a study that demonstrates that this intervention causes mood changes in
any patients who have not been treated with antidepressants.
"In general, several
findings support the fact that depression may not be caused solely by an
abnormality of 5-HT function, but more likely by a dysfunction of other systems
or brain regions modulated by 5-HT or interacting with its dietary precursor.
Similarly, the ATD method does not seem to challenge the 5-HT system per se,
but rather triggers 5HT-mediated adverse events."
So if we cannot confirm the
role of serotonin in mood and we have good reason to believe that antidepressant
effect is largely based on belief, then why are we trying to "boost
serotonin"?
Causing imbalances
All you have to do is spend a
few minutes on http://survivingantidepressants.org/ orhttp://beyondmeds.com/ to appreciate that we have created a
monster. Millions of men, women, and children the world over are suffering,
without clinical guidance (because this is NOT a part of medical training) to
discontinue psychiatric meds. I have been humbled, as a clinician who seeks to
help these patients, by what these medications are capable of. Psychotropic
withdrawal can make alcohol and heroin detox look like a breeze.
An important analysis by
the former director of the NIMH makes claims that antidepressants "create
perturbations in neurotransmitter functions" causing the body to
compensate through a series of adaptations which occur after "chronic
administration" leading to brains that function, after a few weeks, in a
way that is "qualitatively as well as quantitatively different from the
normal state."
Changes in beta-adrenergic
receptor density, serotonin autoreceptor sensitivity, and serotonin turnover
all struggle to compensate for the assault of the medication.
Andrews, et al., calls this "oppositional
tolerance," and demonstrate through a careful meta-analysis of 46 studies
demonstrating that patient's risk of relapse is directly proportionate to how
"perturbing" the medication is, and is always higher than placebo
(44.6% vs 24.7%). They challenge the notion that findings of decreased relapse
on continued medication represent anything other than drug-induced response to
discontinuation of a substance to which the body has developed tolerance. They
go a step further to add:
"For instance, in
naturalistic studies, unmedicated patients have much shorter episodes, and
better long-term prospects, than medicated patients. Several of these studies
have found that the average duration of an untreated episode of major
depression is 12–13 weeks."
Harvard researchers also
concluded that at least fifty percent of drug-withdrawn patients relapsed
within 14 months. In fact:
"Long-term
antidepressant use may be depressogenic . . . it is possible that
antidepressant agents modify the hardwiring of neuronal synapses (which) not
only render antidepressants ineffective but also induce a resident, refractory
depressive state."
So, when your doctor says,
"You see, look how sick you are, you shouldn't have stopped that
medication," you should know that the data suggests that your symptoms are
withdrawal, not relapse.
Longitudinal studies demonstrate poor functional outcomes for
those treated with 60% of patients still meeting diagnostic criteria at one
year (despite transient improvement within the first 3 months). When
baseline severity is controlled for, two prospective studies support a worse
outcome in those prescribed medication:
One in which the never-medicated group
experienced a 62% improvement by six months, whereas the drug-treated patients experienced
only a 33% reduction in symptoms, and anotherWHO
study of depressed patients in 15 cities which found that, at the end of one
year, those who weren't exposed to psychotropic medications enjoyed much better
"general health"; that their depressive symptoms were much
milder"; and that they were less likely to still be "mentally
ill."
I'm not done yet. In a retrospective
10-year study in the Netherlands, 76% of those with unmedicated depression
recovered without relapse relative to 50% of those treated.
Unlike the mess of
contradictory studies around short-term effects, there are no comparable
studies that show a better outcome in those prescribed antidepressants long
term.
First Do No Harm
So, we have a half-baked
theory in a vacuum of science that that pharmaceutical industry raced to fill.
We have the illusion of short-term efficacy and assumptions about long-term
safety. But are these medications actually killing people?
The answer is yes.
Unequivocally,
antidepressants cause suicidal and homicidal behavior. The Russian Roulette of
patients vulnerable to these "side effects" is only beginning to be elucidated and may have something to do with genetic
variants around metabolism of these chemicals. Dr. David Healy has worked
tirelessly to
expose the data that implicates antidepressants in suicidality and violence,
maintaining a database for reporting, writing, and lecturing about
cases of medication-induced death that could make your soul wince.
What about our most
vulnerable?
I have countless patients in
my practice who report new onset of suicidal ideation within weeks of starting
an antidepressant. In a population where there are only 2 randomized trials, I
have grave concerns about postpartum women who are treated with antidepressants
before more benign andeffective interventions such as dietary modification and thyroid
treatment. Hold your heart as you read through these reports of women who took their own and their
childrens' lives while treated with medications.
Then there is the use of
these medications in children as young as 2 years old. How did we ever get the
idea that this was a safe and effective treatment for this demographic? Look no
further than data like Study 329, which cost Glaxo Smith
Klein 3 billion dollars for their efforts to promote antidepressants to
children. These efforts required ghost-written and manipulated data that
suppressed a signal of suicidality, falsely represented Paxil as outperforming
placebo, and contributes to an irrepressible mountain of harm done to our children by the
field of psychiatry.
RIP Monoamine Theory
"Our analysis indicates
that there are no specific antidepressant drugs, that most of the short-term
effects of antidepressants are shared by many other drugs, and that long-term
drug treatment with antidepressants or any other drugs has not been shown to
lead to long-term elevation of mood. We suggest that the term "antidepressant"
should be abandoned."
So, where do we turn?
The field of psychoneuroimmunology dominates the research as an iconic
example of how medicine must surpass its own simplistic boundaries if we are
going to begin to chip away at the some 50% of Americans who will struggle with
mood symptoms, 11% of whom will be medicated for it.
There are times in our
evolution as a cultural species when we need to unlearn what we think we know.
We have to move out of the comfort of certainty and into the freeing light of
uncertainty. It is from this space of acknowledged unknowing that we can truly
grow. From my vantage point, this growth will encompass a sense of wonder –
both a curiosity about what symptoms of mental illness may be telling us about
our physiology and spirit, as well as a sense of humbled awe at all that we do
not yet have the tools to appreciate. For this reason, honoring our
co-evolution with the natural world, and sending the body a signal of safety through movement, diet, meditation, and
environmental detoxification represents our most primal and most powerful tool
for healing.