Depression is a debilitating
condition and a major public health problem. It is the top-ranking cause of
non-fatal disease burden in Australia, accounting for eight percent of the
total years lost due to disability in 1996 1. It is predicted to be
the second largest cause of disability in Australia by the year 2020 2.
Depression is a mental disorder that has the potential to greatly impact one’s
everyday activities. The experience of depressed mood, insomnia, loss of
energy, irritability and other symptoms are commonly linked with depression.
Further, recent research demonstrates its association with inflammation.
Unfortunately, although we
continue to diagnose and medicate people for depression, there is little
science and certainly no evidence to continue to prescribe antidepressants to
most individuals. There are more myths in this area than there are facts and,
as a result, many people are led astray by an industry that makes huge amounts
of money from people’s suffering.
Depression
theory
It is important to understand
that most of what we know about the biochemistry and physiology of depression
is theory and not fact. It is an hypothesis but is often presented by
professionals as truth, with the connotation that these professionals know the
full truth about depression. No, in fact, they do not. What we do know is that
serotonin is located in the pineal gland, blood platelets, the digestive tract
and the brain. Serotonin acts as a chemical messenger that transmits nerve
signals between nerve cells and also causes blood vessels to narrow 3.
We know that there are many other chemical messengers in the body that can have
an impact on our mood and state of wellbeing.
Traditionally it has been
thought that drugs most commonly used to treat depression—the selective
serotonin reuptake inhibitors (SSRIs) such as Prozac® and Zoloft®—act according
to the serotonin hypothesis. This hypothesis purports that levels of serotonin
in the brain determine how we feel: high levels of serotonin cause heightened
happiness, while decreased levels lead to sadness. Clinical depression has been
attributed to low levels of serotonin transmission in the brain 4.
The serotonin transporter 5-HT is a reuptake molecule that removes serotonin,
so it is thought that the SSRIs act to interfere with the action of 5-HT and
therefore allow serotonin to accumulate and levels to increase 4.
This theory is still strongly supported by the pharmaceutical industry 5,
which even uses it to encourage people to “correct” their serotonin levels in
advertising for the drugs 6.
More recently, this theory has
received much criticism as neuroscience research has failed to confirm “any
serotonergic lesion in any mental disorder” 6. That is, the theory
is just not supported by evidence. A growing body of research disagrees with
the serotonin hypothesis 6,7,8. In support of this, a Cochrane
review found that tricyclic antidepressants are of the same efficacy as SSRIs 8.
Since tricyclics do not impact serotonin levels, this would suggest that the
serotonin hypothesis has been disproved. But someone forgot to tell the drug
companies and professionals who continue to aggressively dish out these drugs.
Despite the blind acceptance of
the serotonin theory, the GlaxoSmithKline website has posted: “There is no
clear cut reason for depression, and a number of factors may be at play,
including altered levels of chemical messengers (neurotransmitters) in the
brain, such as serotonin and noradrenaline” 9. If antidepressants
were a cure for depression, there would be a definite illness, with definitive
symptoms and causes that the drugs are targeting. GlaxoSmithKline’s statement
does not support this case.
Antidepressants describe the
broad range of medications prescribed to alleviate the symptoms of certain
depression- and anxiety-related mood disorders and include a number of
different groups of medications. These include monoamine oxidase inhibitors
(MAOIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs),
serotonin-norepinephrine reuptake inhibitors (SNRIs), and the current standard
treatment group: selective serotonin reuptake inhibitors (SSRIs), which became
immensely popular in the 1990s 10.
The first antidepressant that
came along with a huge fanfare was Prozac®. Prozac® appeared on the market in
1988 and is still being prescribed today. It has become one of the most
prescribed drugs to date 11. Prozac® is part of a class of
antidepressants known as selective serotonin reuptake inhibitors (SSRIs).
The prescription of antidepressants
has skyrocketed over recent decades 10. From 1996 to 2005,
individuals treated with antidepressants became more likely to also receive
treatment with antipsychotic medications and less likely to undergo
psychotherapy—the net result is more drugs and less treatment. The percentage
of the U.S. population using at least one psychotropic medication increased
from 5.9% in 1996 to 8.1% in 2001 12. Among
the psychotropic drugs, antidepressants are the most frequently prescribed
medications. The U.S. CDC found that antidepressant use in the United States
jumped nearly 400% by the 2005-2008 survey period, compared with the 1988-1994
period, with 11% of those over age 12 taking the drugs (U.S. CDC and
Prevention’s National Center for Health Statistics) up from six percent in 1996
13.
Antidepressants are now used by
more than 27 million Americans, most of whom are women 14. Women are
twice as likely as men to be diagnosed with major depressive disorder and up to
three times more likely to be diagnosed with dysthymic disorder 15.
However, despite the absence of any scientific evidence, antidepressants are
increasingly being prescribed for other conditions such as hot flashes,
headache, back pain, neuropathy, sleep-related conditions, anxiety spectrum
disorders, eating disorders and fibromyalgia 16. Once prescribed,
many people continue taking antidepressants, with more than 60% of Americans
who use the drugs reporting being on them for two years or more. And about 14% of
Americans taking antidepressant medication have done so for 10 years or longer.
Patients who take the drugs often get them from their regular doctor rather
than a so-called mental health professional.
Last year in Australia, there
were 29 million prescriptions written for medications related to mental health
issues. Antidepressant medications accounted for nearly 60% of these scripts,
followed by anti-anxiety and anti-psychotic drugs 17. This suggests
that around 2.4 million Australians are using medication to deal with mental
health issues.
In the United States, “The
number of visits by patients for depression was 24.5 million in 2001, a 70%
increase since 1987” 18. The ambiguous nature of depression has
provided leeway for significant misdiagnosis. The difficulty in identifying
valid cases of depressive disorder lies within its tendency to share unclear
boundaries with other mental disorders and normality 19. The
distinction between major depression and sadness, for instance, has become
completely obscure. Previously, depression was classed as either endogenous or
reactive 19. Endogenous depression was regarded as a rare biological
condition, whereas reactive depression was exogenous and triggered by stressful
events outside our control, such as the loss of a loved one 19.
Under the Diagnostic and
Statistical Manual (DSM-III), the diagnosis of clinical depression requires the
presence of at least five of the possible nine symptoms for at least two weeks.
Some of these symptoms include loss of interest in usual activities, depressed
mood, fatigue, insomnia and lowered appetite. Yet many of these symptoms can be
seen in natural responses to stress, loss 19, illness, fatigue and
poor sleep. Unfortunately this weak criterion translates into a “low threshold
for diagnosing clinical depression” 20. This suggests that there are
huge risks in misdiagnosing normal emotional states as clinical illnesses. As
an example, chronic fatigue is also commonly mistaken for depression due to the
large overlap in symptoms. In one study involving 3,200 individuals, patients who
were depressed in the beginning of the study were found to be four times more likely
to be fatigued, rather than “depressed” 21. Alas, due to the reinforcing
nature of depression and fatigue, diagnosis becomes difficult.
Considering the major
ambiguities surrounding the concept of depression, it is not surprising that
the quantity of prescriptions for antidepressant medication is so high. What is
of most concern is the number of people who are taking antidepressants and
exposing themselves to unnecessary risk and, in too many cases, are not taking
action to resolve underlying issues.
In a later analysis of additional data, Kirsch supported his
earlier findings and reported antidepressants may be more effective than a
placebo only in severe depression 23. Now with more than a dozen
major meta analyses, the research continues to show there is little supporting
evidence that antidepressants work when placebos appear to be just as—and in
some case more—effective. The research also shows the long-term effects tend to
be severe 22,23,24,25,26,27. In the majority of studies, antidepressants
performed the same as inactive placebo pills.
A recent study found that a minority of antidepressant users
actually fared worse than placebo users. In this study, researchers randomly
assigned 156 depression patients to either take the antidepressant sertraline
(Zoloft® and other brands) daily for 16 weeks or be in a placebo group given
inactive pills. After 16 weeks, there were no overall differences in how the
groups fared 28. Of the antidepressant patients, 31% were treatment
“responders,” meaning they had fallen below a certain score on a standard
measure of depression symptoms, or had seen their score drop at least 50%. The
same was true of about 28% of patients in the talk-therapy group, and 24% in
the placebo group. The differences among the three groups were so small as to
likely be due to chance 28.
Two even bigger reviews in 2010 came to the same conclusions.
A review of four meta analyses of efficacy trials submitted to the U.S. Food
and Drug Administration (FDA) suggests that antidepressants are only
“marginally efficacious” compared with placebo and “document profound
publication bias that inflates their apparent efficacy.” In addition, when the
researchers analysed the largest antidepressant effectiveness trial ever
conducted, they found that “the effectiveness of antidepressant therapies was
probably even lower than the modest one reported... with an apparent
progressively increasing dropout rate across each study phase” due to side
effects 29. A review of nine studies involving 751 participants
found that, from the results presented, antidepressants had only a small
positive effect when compared to an active placebo 30. Other studies
have also shown St John’s Wort to be more effective than an SSRI 31 and
exercise to be at least as effective in older patients 32.
Other irregularities were seen in the data. It was noted
that published data consisted entirely of positive outcomes and that many of
the negative trials’ reports were not published or that negative data were displayed
in a positive manner 25,26.
Publication bias, where only the positive results are reported and
published, is well known in the drug industry and just a part of the drug
companies’ everyday lies and deception.
Despite the findings of researchers, the FDA in the U.S.
reports that 94% of its studies have shown positive results, with
antidepressants found to be effective in treating depression 33.
However, publication of antidepressant studies by the FDA is highly selective:
“The studies that the FDA judged as positive were approximately 12 times as
likely to be published in a way that agreed with the FDA analysis as were
studies with non-positive results according to the FDA” (Turner et al. 2008).
Why have the FDA in the U.S. and Australian regulatory authorities continued to
go against the scientific evidence?
The likely benefit of antidepressants is the placebo effect 23,25.
In trials, the patients on placebos would see the doctor on a weekly basis for
check-ups and to update the analysts for the report. In addition, the patients were
within easy access to help 24 hours a day 26,34. Thus, the amount of
human contact, attention and care skews the results 26. This could
possibly reveal the reason the placebo had such a strong effect. Imagine the
positive feeling from being closely cared for by your medical practitioner,
including having his or her phone number, rather than just in and out of the
office in 12 minutes. The amount of attention and care influenced the strength
of the placebo. Under real-world conditions, the patient sees the doctor less
frequently and is less likely to seek help 26,34.
The actual efficacy of SSRIs, therefore, remains in question
and often subject to the merits and interests of those conducting a particular
study. Many people drop out of drug trials because of the seriousness of side
effects. The serotonin receptors are responsible for a variety of functions
unrelated to mood, such as sleep, appetite and sexual function, as well as
symptoms such as pain, nausea, depression, and anxiety 35. Common
side effects of taking an SSRI include nausea, dizziness, gastrointestinal
disturbances, anxiety, agitation, insomnia, sexual dysfunction and weight gain 35.
Significant literature exists documenting the symptoms of SSRI discontinuation
syndrome, which range from moderate to severe 36. There can also be
more serious consequences: SSRI use has been linked to serotonin syndrome,
birth defects and high risk of suicide. The link between antidepressants and
suicide has been recognised for at least 20 years and the United States FDA
requires that antidepressants carry a label warning of this increased risk on
each box 37. In such cases it would seem antidepressants are not
effective at all and, in fact, can have serious and even deadly side effects.
Despite these findings that
have now been repeated many times, “professionals” working in the field still
state that antidepressants work and continue to prescribe them to more and more
people.
It is also worth pointing out
that in the United States, until 1990 tryptophan dietary supplements were being
taken by approximately 15 million Americans. On March 22, 1990, the Food and
Drug Administration (FDA) banned the sale of L‑tryptophan in response to
several deaths during the previous year from a deadly flu‑like condition called
EMS 38. This is despite L-tryptophan having been used as a
supplement for decades prior to this, by a large number of people, without any
adverse side effects. The problem was caused by a contaminated batch of
tryptophan, not the tryptophan itself. One wonders why it was banned, as most
drugs including antidepressants would be removed from the marketplace if this
principle were applied across the board, including drugs that have been linked
with hundreds of thousands of deaths.
However, on March 26, 1990,
only four days after the banning of L-tryptophan, Prozac®, the wonder drug in
the treatment of depression, was introduced with great fanfare after more than
10 years of development. What a coincidence. As mentioned earlier, Prozac® is
an SSRI, whilst tryptophan actually increases the serotonin levels in the body.
Other interesting facts about
this controversy:
L‑tryptophan was banned as a
dietary supplement in the United States and Australia until 2005. It could,
however, be imported from Japan and became available as a prescription-only
drug. One hundred 500 mg capsules cost approximately $75.00. This is about five
times more expensive than its previous cost as a dietary supplement.
L‑tryptophan is still used in
baby food produced and sold in the United States.
Farmers are still allowed to
use it in stock feed for animals. I wonder if this is because happy animals are
more likely to gain weight?
1. Mathers
et al. 2000
2. Minas
et al. 2007
3. MedicineNet
2003
4. Schafer
1999
5. Cowen
2008
6. Lacasse
and Leo 2005
7. Murphy
1998
8. Geddes
et al. 2005
9. GlaxoSmithKline
2008
10. Olfsen
et al. 1998
11. Wrobel
2007
13. Olfson
et al. 2009
14. Cosgrove
et al.
15. American
Psychiatric Association 2000
16. Roberts
2007
17. Australian
Institute of Health and Welfare
18. Fergusson
et al. 2006
19. Parker
2007
20. Lucassen
et al. 2007
21. Skapinakis
2004
22. Kirsch
2002
23. Johnson
and Kirsch 2008
24. Kirsch
and Moncrieff 2005
25. Ioannidis
et al 2008
26. Posternak
and Zimmerman 2007
27. Crawford
and Parker 2007
28. Barber
2011
29. Pigott
et al. 2010
30. Moncrieff
et al. 2010
31. Szegedi
et al. 2005
32. Blumenthal
et al. 1999
33. Turner
et al. 2008
34. Blier
2008;
35. Ferguson
2001
36. Haddad
1998
37. Reeves
and Ladner 2010
38. Manders
1995
Acknowledgements
Shannon Fitzgerald , Ben Gundry, Kahlia Belli, Noratiah
Larry, Grant Swan and Jan van der Walt, Geraldine Treloar
Is it possible to have access to the full references to this interesting article? I'd love to investigate further. Thanks.
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