The simple take home is
that no prescription drug protocol appears to be satisfactory in the long term
treatment of mental illness. Obviously
other methods need to be exhausted and then drugs need to be applied briefly in
order to attempt to establish normalcy.
It is really very disconcerting that the present protocols are not
solutions at all but a deadly game of trial and error played out when victims
are least able to manage themselves and
their treatment.
The author reviews the
present state of the art and raises cautions regarding new drug fads that need
to be better addressed.
Mental illness needs to
be confronted with a 24/7 disciplined training protocol that works all aspect
of the mind and the body to strengthen the organism itself to find its own work
around. At worst the victim has
increased capacity and that is welcome.t
A Psychiatrist’s
Perspective on Using Drugs
January 20, 2014
Kelly Brogan,
MD,
When I see new patients, I do not prescribe
medication for them. Patients who come to me know that I plan to help them
understand “why” they are experiencing “what” they are going through.
Once I have
tapered patients off of medication, we use alternatives if symptoms crop up
again.
Knowing my basic
orientation around the issue of psychiatric prescribing doesn’t seem to stop
some patients from asking for what they believe will be a quick fix in an
antidepressant pill. Where did they learn to make these treatment
requests of providers?
Perhaps they are
a reflection of the 49% of requests for drugs prompted by “direct-to-consumer”
(DCA) advertising by pharmaceutical
companies.1 Fully 7 out of 10 times, doctors
prescribe based on these requests made by patients who learned from advertising
that they have an “imbalance” that must be fixed with a pill.
In a 10-year
period from 1999 to 2008, DCA tripled from 1.3 to 4.8 billion dollars devoted
to educating patients about their need for psychiatric medication. The
“mass provision” of SSRIs to the public is not a reflection of their
well-understood mechanism, of their efficacy, or of their safety. In fact, it
flies in the face of all three.
As stated by
Professor of Neuroscience, Elliot Valenstein:2 “What physicians and the public
are reading about mental illness is by no means a neutral reflection of all the
information that is available.”
Reasoning Backwards:
What Are We Treating?
If you were to ask the average person on the
street what the biology of depression relates to, they would very likely
parrot, “serotonin deficiency.” This hypothesis, referred to as the monoamine
hypothesis, grew out of observations of mood-related side effects in the
treatment of tuberculosis patients with iproniazid,3 which has some inhibitory impact on
the breakdown of monoamines.
From this accidental observation and double
talk about reserpine’s role in inducing and treating depressive states, a
theory was born. Six decades of subsequent studies in never-medicated
depressed patients have been conflicting, confusing, and inconclusive, and a
critical review of the hypothesis concludes:4
” … there is no
direct evidence of serotonin or norepinephrine deficiency despite thousands of
studies that have attempted to validate this notion.”
Similarly conclusive is a New England Journal of Medicine review
on Major Depression,5 which 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.”
Even in the pursuit of this appealingly
reductionist idea of a chemical deficiency, we are unable to measure central
nervous system quantities, to account for the inner workings of 14 different
types of serotonin receptors,
Also for the vast projections of serotonin
trafficking neurons, and for the delicate interplay between the 100 some
neurotransmitters that we know to be active in the brain. Dr. Daniel Carlat,
author of Unhinged,
writes:
“We have convinced
ourselves that we have developed cures for mental illnesses…when in fact we
know so little about the underlying neurobiology of their causes that our
treatments are often a series of trials and errors.”
How Do These Meds
Work?
Even if we were to accept the premise that
these medications are helpful, extrapolating a medical etiology from this
observation would be the same as saying that shyness is a deficiency of
alcohol, or migraine a deficiency of codeine.
And to my holistic and integrative colleagues
who are very excited about tryptophan and 5HTP in medication-naïve patients, I
will remind them that the only time that tryptophan depletion has correlated
with low mood is in those patients previously treated with SSRIs.
We have been taught to associate serotonin
with feeling good, but the fact is that high serotonin has been associated with
feeling bad, including carcinoid
syndrome, Alzheimer’s, autism, and schizophrenia.
Low serotonin metabolite (5H1AA) is indicative
of turnover of serotonin, and is the eventual result of increased serotonin in
the synapse. This has been associated with suicide, violent crime, alcoholism,
bulimia, and exhibitionism! Clearly, we are not dealing with a simple more
is better, or even a “looking for the right balance” type of scenario.
Chasing this pattern and seeking to alter
“levels” is like trying to connect a pile of scattered dots into a long
straight line – you have to ignore the ones that don’t fit. What about genetics? Wasn’t I born with this
defect?
Despite the continued efforts to identify “the
gene,” a false start in 2003,6 which suggested that those with a
variant in the serotonin transporter were 3x more likely to be depressed, was
later mowed over by a meta-analysis of 14,000 patients that denied this
association.7 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.”
Carlat goes on to say:
“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.”
Pharma Weaves an
Irresistible Tale
Eleven billion dollars are spent each year on
antidepressant medications,8 pharmaceutical
companies have 625 lobbyists,9and
they underwrite more than 70% of FDA trials. They court physicians,10 give
them samples, tell patients to “ask their doctor,” pay consultants to speak at
scientific meetings, advertise in medical journals, fund medical education, and
ghostwrite, cherry pick and redundantly submit data for publication.
Psychiatric studies funded by pharma are 4x more likely to be published
if they are positive,11 and
only 18% of psychiatrists are disclosing their conflicts of interests when they
publish data. Their studies allow:
·
Placebo
washout (getting rid of those who are likely to respond to placebo
before the study to strengthen the perceived benefit)
·
Replacement
of non-responders
·
Breaking
blind by using inert placebos so that subjects know
that they have received the treatment
·
Use
of sedative medications concurrent to study medications
A now famous 2008 study in the New England Journal of Medicine12 by Turner et al sought to expose the extent of data
manipulation. Through valiant efforts to uncover unpublished data, they
determined that from 1987 to 2004, 12 antidepressants were approved based on 74
studies. 38 were positive, and 37 of these were 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.
Since two studies are required by the FDA for
approval, you can see how these companies are tossing the coin repeatedly,
until heads comes up, and hoping no one is looking when it’s tails. Per Robert
Whitaker, author of Anatomy of An
Epidemicand Mad In America,
references, these practices undermine the accuracy of data and deliver
information that corrupts physician’s delivery of care and endangers patients.
The costs of this manipulation of information
is the loss of true informed consent – physicians cannot
adequately share with patients the risks and benefits if the benefits are
fabricated and the risks are not uncovered (by 5-6 week trials) or are
unacknowledged.
Placebo Effect – Why
They “Work”
Despite Pharma’s efforts, the truth about
these brain bombs is emerging. In 1998, Dr. Irving Kirsch, an expert on the
placebo effect, published a meta-analysis13 of
3,000 patients who were treated with antidepressants, psychotherapy, placebo,
or no treatment and found that 27% of the therapeutic response was
attributable to the drug’s action.
This was followed up by a 2008 review,14 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 my
medication side effects strategically employed (sedation or activation).
He found that severely depressed patients were
less placebo responsive, generally, potentially accounting for the impression
of some increased benefit, such as that found by Fournier et al.15 When
active placebos were used, the Cochrane database16found
that differences between drugs and placebos disappeared, given credence to the
assertion that inert placebos inflate perceived drug effects.
In response to 2005 recommendations from the
National Institute for Health and Clinical Excellence that SSRI medications be
first line treatment recommendations for depression, Drs. Kirsch and Moncrieff
pointed out17 that
the NICE data, itself, demonstrates a 1 point difference on the 52 point
Hamilton Scale between placebo and drug groups, and that it was not in more
severely depressed patients that this was found.
The finding of tremendous placebo effect was
also echoed in two different meta-analysis by Khan et al18 who
found a 10% difference between placebo and antidepressant efficacy, and
comparable suicide rates. The largest, non-industry funded study,19 costing
the public $35 million dollars, followed 4000 patients treated with Celexa (not
blinded, so they knew what they were getting), and 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. Only
3% of patients were in remission at 12 months.
So what if it’s
placebo effect? It’s working at least some of the time, so who cares? Here’s
why I, and other concerned psychiatrists and practitioners, care: I first
became aware of the habit forming nature of these medications when I tapered a
patient off of Zoloft in anticipation of a pregnancy in the coming year, and
she experienced about 6 months of protracted withdrawal that began at about two
months after the last dose. This was nothing I was prepared, by my training, to
deal with.
What are these medications actually
doing?! The truth is, we have very little idea. We like to cling to
simple explanations, but even the name of the various antidepressants, selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitorsis
misleading.
They are far from selective. An
important analysis20 by
the former director of the NIMH makes claimed that antidepressants “create perturbations in neurotransmitter functions”
causing the body to compensate through a series of compensatory 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.” [ this is called an
unintended consequence, otherwise known as a bad idea – arclein ]]
Changes in beta-adrenergic receptor density,
serotonin autoreceptor sensitivity, and serotonin turnover all struggle to
compensate for the assault of the medication.
Andrews et al21 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 suggest:
“For instance, in
naturalistic studies, unmedicated patients have much shorter episodes, and
better long-term prospects, than medicated patients (Coryell et al., 1995;
Goldberg et al., 1998; Posternak et al., 2006). Several of these studies have
found that the average duration of an untreated episode of major depression is
12–13 weeks (Coryell et al., 1995; Posternak et al., 2006).
Since acute ADM
management of major depression minimally requires several weeks to reduce
symptoms, the duration of untreated episodes is much shorter than the
recommended duration of ADM therapy. This suggests that ADM therapy may delay
resolution of depressive episodes.”
Harvard researchers22 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.”23
Buyer Beware
Here we come to the little disclosed poor
outcomes associated with long-term treatment.
We won’t focus on the risk of suicide and violence, bleeds, or even suppressed
libido and sexual dysfunction, indifference (or “medication spell-binding” as
Dr. Peter Breggin calls it), or weight gain and dysglycemia. Let’s just
focus on what the data shows on how your ability to function, long-term, in the
world with depression is significantly sabotaged by treating that first episode
of depression with medication.
This was famously explored by Robert Whitaker,
and can be summarized with the following studies, as a primer. Longitudinal
studies demonstrate poor functional outcomes for those treated with 60% of
patients still meeting diagnostic criteria at one year24 (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,25 and
another WHO 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.”26
I’m not done yet. In a retrospective 10-year
study27 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.
Perhaps most concerning to a holistic
physician is data28 that
suggests that long-term antidepressant treatment actually compromises the known
and evident benefits29 of
exercise! Benefits of exercise treatment of depression were comparable to
Zoloft and were diminished when combined with Zoloft where patients relapsed at
higher rates than they did with exercise alone.
Selling Sickness
Whitaker helps us to remember: Prior to the
widespread use of antidepressants, the National Institute of Mental Health told
the public that people regularly recovered from a depressive episode, and often
never experienced a second episode.30 Now
we have skyrocketing rates of disability in the setting of skyrocketing
prescriptions. Whitaker has compiled and analyzed data demonstrating that
days of work lost are increased by medication treatment as is long-term
disability (19% vs 9%),31 3-7
times the incidence of loss of “principal social role” and “incapacitation,”32 with
treated illness, and that 85% of unmedicated patients recover in a year, with
67%33 doing
so by 6 months – an enviable statistic.
What has happened
here? Since its 1952 inception and notorious
inclusion of homosexuality as a diagnosable syndrome, the Diagnostic and
Statistical Manual has now ballooned to more than 300 diagnoses in its fifth
edition, all arrived at through general consensus of a committee consisting of
practitioners with conflicts of interest34 and
pharmaceutical enmeshments. Allen Frances at Columbia states:
“Wholesale imperial
medicalization of normality that will trivialize mental disorder and lead to a
deluge of unneeded medication treatment – a bonanza for the pharmaceutical
industry but at a huge cost to the new false positive patients caught in the
excessively wide DSM-V net.”
We need to break the populace out of its
spell, reject the serotonin meme, and start looking at depression (and anxiety,
and bipolar, and schizophrenia, and OCD, etc) for what they are – disparate
expressions of a body struggling to adapt to a stressor. We need to
identify vulnerabilities, modifiable exposures, and support basic cellular
function, detox, and immune response. This is personalized medicine, where
these abstract labels become meaningless because they only address the “what”
of the symptoms” in an impressionistic, non-specific manner. One as
helpful as saying the fever is the disease, and Tylenol the cure. Psychiatry’s
swan song has been sung…listen for its plaintive wail.
About the Author
Dr. Brogan is boarded in Psychiatry/Psychosomatic
Medicine/Reproductive Psychiatry and Integrative Holistic Medicine, and
practices Functional Medicine, a root-cause approach to illness as a
manifestation of multiple-interrelated systems. After studying Cognitive
Neuroscience at M.I.T., and receiving her M.D. from Cornell University, she
completed her residency and fellowship at Bellevue/NYU. She is one of the
only physicians with perinatal psychiatric training who takes a holistic
evidence-based approach in the care of patients with a focus on
environmental medicine and nutrition. She is also a mom of two, and an active
supporter of women’s birth experience, rights to birth empowerment, and
limiting of unnecessary interventions which is a natural extension of her
experience analyzing safety data and true informed consent around medical
practice. She is the Medical Director for Fearless Parent, and an
advisory board member for GreenMedInfo.com and Pathways to Family Wellness. She practices in NYC and
is on faculty at NYU/Bellevue.
Disclaimer: This article is
not intended to provide medical advice, diagnosis or treatment. Views expressed
here do not necessarily reflect those of WakingTimes or its staff.
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