Evidence-biased Antidepressant

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Flawed Research, and Conflicts of
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Evidence-biased
Antidepressant Prescription
Overmedicalisation,
Flawed Research,
and Conflicts of Interest
Michael P. Hengartner
Evidence-biased Antidepressant Prescription
 Michael P. Hengartner

Evidence-biased
Antidepressant
Prescription
Overmedicalisation, Flawed Research,
and Conflicts of Interest
Michael P. Hengartner
School of Applied Psychology
Zurich University of Applied Sciences
Zurich, Switzerland

ISBN 978-3-030-82586-7    ISBN 978-3-030-82587-4 (eBook)

https://doi.org/10.1007/978-3-030-82587-4

© The Editor(s) (if applicable) and The Author(s), under exclusive licence to Springer Nature
Switzerland AG 2022
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 Contents

1 Introduction: How Did I Get Here?  1

2 Antidepressants in Clinical Practice 11

3 The Transformation of Depression 47

4 Flaws in Antidepressant Research113

5 Conflicts of Interest in Medicine165

6 Solutions for Reform241

References265

Index351

v
 List of Tables

Table 2.1 Popular antidepressants for the treatment of depression still

on the market 13
Table 4.1 Common methodological limitations in double-blind
randomised controlled trials 124
Table 6.1 Possible solutions to end corporate bias in medical research,
education, and practice adopted from Moynihan and
colleagues [380] 262

vii
 1
Introduction: How Did I Get Here?

Medicine is supposed to make progress, to go forward in scientific terms so

that each successive generation knows more and does better than previous
generations. This hasn’t occurred by and large in psychiatry, at least not in
the diagnosis and treatment of depression and anxiety, where knowledge
has probably been subtracted rather than added. There is such a thing as
real psychiatric illness, and effective treatments for it do exist. But today
we’re seeing medicines that don’t work for ill-defined diagnoses of dubious
validity. This has caused a crisis in psychiatry … In the rather ineffective
drug treatments for depression known as the selective serotonin reuptake
inhibitors (SSRIs)—the Prozac-style drugs—and in the triumph of such
diagnoses as ‘major depression’ that exist more in the shadowland of arti-
fact than in the world of Nature—academic psychiatry has a lot to
answer for [1].

I believe that the enduring skepticism and distorted views about antide-
pressant drugs are due to the stigma of mental illness and prejudice toward
the medical specialty responsible for its study and care. This historical
stigma is perpetuated by lay and professional groups, who oppose the use
and deny the efficacy of psychotropic medication for ideologic reasons or
organizational biases. Psychiatry has the dubious distinction of being the
only medical specialty with an anti-movement that is constantly challeng-

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 1

M. P. Hengartner, Evidence-biased Antidepressant Prescription,
https://doi.org/10.1007/978-3-030-82587-4_1
2 M. P. Hengartner

ing and undermining the field. The other source of opposition comes from
anti-scientific or anti-medical groups who draw the battle lines along
whether medical or psychotherapeutic treatment modalities can or should
be used … Doctors should not be fooled by the pharmacologic naysayers,
and no patient with major depressive disorder should be denied the effec-
tive treatment that can be hugely beneficial for them [2].

The provocative critique by Dr Edward Shorter, a medical historian,

and the typical defence of the drug-centred treatment approach in depres-
sion by Dr Jeffrey Lieberman, eminent professor of psychiatry and for-
mer president of the American Psychiatric Association (APA), illustrate
nicely the controversial questions this book will address. Dr Shorter is by
no means the only one who has questioned the validity (and utility) of
our current definition of “major” depression, and the opposition to this
ill-conceived diagnosis comes from psychiatrists, general practitioners
(GPs), and psychologists alike [3–7]. How the concept of depression has
changed over time and how this mental disorder—its putative aetiology
(causation), phenomenology (experience), prevalence (frequency), course
(trajectory), and disability burden (impairment)—is portrayed in con-
temporary scientific discourse and the media is the first main topic of
this book.
Like Dr Shorter, many authors, again psychiatrists, GPs, and psychol-
ogists alike, consider the effectiveness of the SSRIs and other new-­
generation antidepressants poor and of doubtful clinical relevance in the
average patient with depression [8–13]. My own analyses of clinical trials
and my scrutiny of the scientific literature led me to similar conclusions
[14–20]. Yet, I’m fully aware that the scientific evidence is ambiguous
and that there is considerable variability in how the data can be inter-
preted. Like Dr Lieberman in his quote above, most psychiatrists, espe-
cially academic leaders in the field, resolutely dismiss negative conclusions
regarding the effectiveness of antidepressants as ideologically biased anti-­
psychiatric propaganda devote of scrutiny and scientific justification and
contend that these drugs are highly effective and safe in depression (see,
for example [21–23]). These polarised and angry debates over the scien-
tific evidence for (or against) antidepressants in depression are the second
main topic of this book.
 1 Introduction: How Did I Get Here? 3

And then there is the pervasive influence of the pharmaceutical indus-

try that has made billions of dollars in revenues with the marketing of
both “major” depression as a brain disease and its putative cure, the new-­
generation antidepressants [9, 14, 24–26]. By necessity, every critical
analysis of antidepressant prescribing for depression must thus address
conflicts of interest and corporate bias in psychiatry and primary care
medicine [9, 27–30]. This is the third main topic of this book.

 he Inconvenient Truth about

T
Scientific Research
Over my academic career, I went into different stages of belief and disbe-
lief. I studied clinical psychology and psychopathology at the University
of Zurich, Switzerland. Back in the early 2000s, we were taught about
psychiatric diagnoses as if these were clear-cut natural disease entities.
Our curriculum strictly followed the disorder categories outlined by the
Diagnostic and Statistical Manual of Mental Disorders (DSM) of the
APA. I can’t remember that we ever had a critical discussion about the
validity and utility of these diagnoses. The DSM was like a bible, an
authoritative and definite resource that contains wisdom and ultimate
knowledge. When a student asked something about a specific mental
disorder, the professors typically answered that this is true or not because
the DSM says so. The DSM was axiomatic, dogmatic, and conclusive.
We also learned that antidepressants were safe and effective, and within
my memory there never was mention of limitations or biases in the evi-
dence base. The validity and reliability of most research findings was
barely questioned. In general, we were taught about psychological experi-
ments as if these provided definitive answers to fundamental questions of
human being. Findings from seminal studies were often (not always)
considered irrefutable truths about human behaviour, cognition, and
emotion. I was taught that this is how humans think, behave, and feel
because it has been confirmed in this or that study. I never considered
that many, perhaps most of these studies, could be simply wrong.
4 M. P. Hengartner

I had my first doubts about the credibility (and quality) of research

findings when I was conducting the statistical analyses for my master
thesis. I had been working on a project about testosterone, sensation
seeking, and fatherhood. I soon realised that data from such an observa-
tional study was prone to many biases and confounders. I also learned
that removing one or two outliers, using different operationalisations of
the same construct, and adding certain control variables to a statistical
model could produce completely divergent results. I started to wonder if
the authors of the seminal psychological studies we were taught in class
also had come up with completely divergent results had they not deliber-
ately chosen to analyse their data in a specific way. Could it be that they
also ran multiple statistical models and then selectively reported the
results that provided the neatest and most persuasive answer, that is, the
results that confirmed their preconceived beliefs?
In Spring 2009, soon after I had obtained my Master of Science in
clinical psychology and psychopathology, I started to work as a research
associate at the Department of General and Social Psychiatry of the
Psychiatric University Hospital of Zurich. I started my PhD project on
the epidemiology of personality disorders under the supervision of pro-
fessor of psychiatry Dr. Wulf Rössler, the then-director of the clinic, and
Dr. Vladeta Ajdacic-Gross, a senior researcher at the department. My
supervisors quickly noted that I was a talented researcher, and in late
Summer 2010, in addition to my appointment as a PhD student, I was
employed as a research associate for Dr. Rössler. We were mostly working
on the data of the prospective Zurich Cohort Study, a community cohort
study of young adults from the canton of Zurich followed over 30 years
[31, 32]. The same year I also became a research associate for professor
Dr. Jules Angst, former research director of the Psychiatric University
Hospital of Zurich and lead investigator of the Zurich Cohort Study.
One main research interest of Dr. Rössler were sub-clinical psychotic
symptoms in the general population [33], so together with Dr. Ajdacic-­
Gross, I was examining if we could replicate the association between can-
nabis use and the occurrence of psychotic symptoms reported in the
literature [34].
Again, I soon realised that different statistical approaches yielded con-
flicting results. The association between cannabis use and psychotic
 1 Introduction: How Did I Get Here? 5

symptoms was not evidently clear from the outset, but I was told that I
must search the data to find the “truth”. Searching the data means to run
various statistical models with changing definitions of predictor and out-
come variables, checking the impact of different control variables on the
results and thus deriving the “best” model. According to this exploratory
approach, the “best” model is the statistical analysis that confirms your
hypothesis. Thus, eventually we were able to demonstrate a prospective
association between cannabis use and the occurrence of psychotic symp-
toms, and we published the results in a leading medical journal [35]. But
was the “best” model necessarily the most accurate model? Did we really
detect a true association, or did we rather adjust our statistical analysis
until it confirmed our hypothesis (also referred to as data dredging or
p-hacking)? As the saying goes, “if you torture the data long enough, it
will confess to anything”. It is now widely accepted that this is poor sci-
entific practice that substantially increases the risk of false positive results,
that is, statistical artifacts or chance findings [36–40]. But back in late
2010, as a PhD student, I simply did what I was told by my supervisors
(and taught in university), even though it didn’t feel right. I was not
aware yet of the compelling scientific literature that strongly advised
against such questionable research practices.
The publication of our cannabis-psychosis paper coincided with the
proclamation of the replication crisis in psychology [41–44]. My intu-
ition that psychological and psychiatric research, and by extension
research in general, was often unreliable, irreproducible, and systemati-
cally biased towards spectacular but most likely false positive findings,
became a prominently discussed hot topic. I was immediately intrigued
by this flood of new research that exposed so many pernicious problems
in contemporary psychological research. In my new position as research
associate for Drs Rössler and Angst I prepared various research papers. I
quickly gained experience in data analysis and I also acquired profound
knowledge in statistics and research methodology. I dug deeper into the
metascience literature and found deeply concerning evidence for what I
have expected for so long, but never was told as a student and junior
researcher. A large portion, presumably a majority, of research findings in
psychology, psychiatry, and biomedicine, is most likely false or massively
exaggerated [45–50]. I learned about p-hacking, the fabrication of
6 M. P. Hengartner

statistically significant results [39], about the flaws and limitations of sta-
tistical significance testing [51], and about publication bias, the selective
reporting of favourable (i.e. hypothesis-confirming) research find-
ings [52].
In 2014, about a year after I had completed my PhD, I left the
Psychiatric University Hospital of Zurich to assume a tenured position at
the Zurich University of Applied Sciences. Metascience, research meth-
odology, statistics, and the philosophy of science became my primary
research interests. I started to write papers about methodological flaws
and research biases and how these can easily produce false-positive results
in biomedical and psychological research [53, 54]. I also wrote about the
systematic biases in psychotherapy research [55]. But my biggest interest
was in antidepressants for depression, and this preference changed my
career fundamentally.

The Issue with Antidepressant Research

In my first year at the Zurich University of Applied Sciences I had been
searching the scientific literature about publication bias in psychiatric
research. This is when I opened Pandora’s box, for when you search the
literature on publication bias in psychiatry, among the first research
papers you’ll find are the seminal studies from the 2000s that demon-
strated how selectively the results of antidepressant trials were published
[56–58]. Next you’ll discover how pervasively the pharmaceutical indus-
try has corrupted academic medicine and that drug manufacturers sys-
tematically bias the scientific evidence so that their products appear more
effective and safer than they really are [28, 59–62]. You will probably also
learn about the various flaws in the contemporary definition of depres-
sion and other mental disorders [7, 63–65] and how mental disorders
were misleadingly marketed by the pharmaceutical industry to increase
the sales of psychiatric drugs [26, 27, 66, 67].
I have always been interested in the research of depression and have
co-authored various papers on mood disorders and negative affectivity
(see, for example [68–76]). I also have lived experience of depression as a
young adult, when I was doing my military service. I didn’t seek
 1 Introduction: How Did I Get Here? 7

treatment back then and fortunately, my profound sadness, lack of inter-

est and pleasure, and feelings of hopelessness that persisted for several
weeks lifted soon after I was discharged from the army. After my recovery
I flourished and, curiously, even felt emotionally stronger than before my
depression episode. I gained a self-esteem and confidence I didn’t have
before. Later I learned that this phenomenon, that is, high functioning
after full recovery from a depression episode, is a widely neglected topic,
but it is presumably not that rare as most psychiatrists and clinical psy-
chologists would think [77]. Thus, the concept and outcome of depres-
sion were interesting to me not only from a scientific perspective, but also
from my personal life story. In 2017, finally, I published my first research
paper on antidepressants for depression, a critical review of methodologi-
cal limitations in clinical trials, selective reporting of research findings,
and corporate bias in the evidence base [14].
This publication, and the many others that would follow, to my sur-
prise (or naivety) also completely changed my research career and posi-
tion within the scientific community. There were already several papers
on these issues in the scientific literature, of which most were published
in leading general medical and psychiatric journals (see, for example, [57,
78, 79]), and various books had been written about it (see, for example
[9, 11, 80]). So I didn’t think that my paper was really big news or that it
would cause a stir. But I was proved wrong and in hindsight I also realise
how naïve I was. Before long, other researchers contacted me and con-
gratulated me on my first antidepressant paper. This is how I met Dr.
Martin Plöderl, psychotherapist and senior researcher at the Christian
Doppler Clinic, Paracelsus Medical University in Salzburg, Austria, who
over time became a friend and close collaborator. Blog authors and jour-
nalists wrote and asked for interviews. With each additional paper on
antidepressants I published there were more interview requests and invi-
tations for talks at scientific meetings. Service users also wrote to me,
mostly people harmed by antidepressants, who thanked me for my edu-
cational work on the risks of antidepressants and conflicts of interest in
psychiatry. Soon I also communicated with influential researchers in this
field, including, among others, Drs David Healy, Peter Gotzsche, Irving
Kirsch, Joanna Moncrieff, Mark Horowitz, Janus Jakobsen, Tom Bschor,
John Read, James Davies, and Giovanni Fava.
8 M. P. Hengartner

But there was not only delight and appreciation for my critical research
on the benefit–harm ratio of antidepressants. Some people, especially
psychiatrists, attacked me fiercely on social media, but also in their
reviewer comments on articles I submitted for publication. Some accused
me of spreading conspiracy theories and misinformation. Akin to Dr
Lieberman in his blanket condemnation of researchers who question the
clinical significance of antidepressants quoted at the beginning of this
book [2], they alleged I was running an anti-scientific, ideologically
biased crusade against psychiatry. My former PhD supervisor, Dr. Wulf
Rössler, who also supported me as co-author on two controversial papers,
once warned me that some leaders in the field would push back hard. He
cautioned that by pursuing this kind of research I would soon make pow-
erful enemies. He was right. There were times I felt exhausted and crest-
fallen, demoralised by insults on social media and irritating ad hominem
attacks by anonymous reviewers.
I soon realised that the debate was highly polarised and hateful. Even
scientific arguments could quickly turn into scathing and discrediting
accusations. But there was also interest in my arguments and honest will-
ingness to discuss the scientific evidence. A few debates were indeed con-
structive, especially when opponents were willing to discuss my scientific
arguments instead of simply attacking me as a person for the kind of
research I do. I also learned that many practicing psychiatrists and GPs
were simply not aware of these pervasive issues that, to me, seemed so
evident after my scrutiny of the literature. Some also admitted honestly
to me, in confidence, that they were not allowed to raise these issues in
the clinic, fearing disapproval and rejection from their colleagues and
supervisors.
After I completed my habilitation (qualification for professorship and
highest academic degree in Switzerland and various other countries) at
the medical faculty of the University of Zurich, I gave my inaugural
speech at the university in February 2019. I lectured about threats to
evidence-based antidepressant prescribing. I detailed the selective report-
ing of efficacy and safety outcomes in antidepressant trials, which lead to
a systematic overestimation of benefits and underestimation of harms.
This is not just a provocative, misinformed opinion (as some psychiatrists
had suggested), it is a well-established scientific fact consistently
 1 Introduction: How Did I Get Here? 9

replicated over many years in antidepressant research [56–58, 81–83]

and across various other therapeutic domains in general medical research
[84–90]. The speech was attended by various colleagues from the
Psychiatric University Hospital of Zurich, of which most were psychia-
trists. After the talk, several came to me and confessed how concerned
they were about these revelations. Never had they thought that the scien-
tific literature was that biased and unreliable. Never during their training
and continuing medical education had they heard about these seminal
studies. I realised back then that this needs to change.
Since the publication of my first paper on antidepressants in 2017, I
have given several talks at general hospitals, psychiatric clinics, and scien-
tific conferences about the corruption of evidence-based medicine and
systematically biased benefit–harm evaluations of antidepressants and
other drugs. The reactions were always the same. The audiences, mostly
physicians from various specialties and other healthcare providers (e.g.
psychologists and social workers), were shocked about these findings.
Quite often they were also embarrassed that they had been so ignorant
about these pervasive issues. Several people asked me why I didn’t write a
book about it. I have long hesitated, as there are already several books and
many research papers about the medical construct of depression, corpo-
rate bias, and antidepressant over-prescribing. However, obviously most
practitioners, but also researchers, service users, advocacy groups and
policymakers, are not aware of the multiple flaws in the way we define,
diagnose, and treat depression. That’s why I wrote this book on antide-
pressant prescribing in depression.
 2
Antidepressants in Clinical Practice

All antidepressants available on the market increase the concentration of

certain neurotransmitters (chemical messengers) in the brain, but how
they exactly work in depression is poorly understood [91-93]. Based on
their primary mechanism of action, antidepressant drugs can be broadly
divided into five major classes. The monoamine oxidase inhibitors
(MAOIs) prevent the breakdown of monoamines, predominantly sero-
tonin, norepinephrine (noradrenaline) and dopamine, and thereby
increase their availability in the synapse. The tricyclics increase the con-
centration of serotonin and norepinephrine by blocking their reuptake
but also have potent antihistaminic and anticholinergic effects. The
selective serotonin reuptake inhibitors (SSRIs) more selectively prevent
the reuptake of serotonin, thus mostly increasing the availability of sero-
tonin. The serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit
the reuptake of both serotonin and norepinephrine, thus primarily
increasing the concentration of these two neurotransmitters. Finally, the
atypical antidepressants are a heterogeneous class with different mecha-
nisms of action, but to some degree all increase the concentration of
serotonin, norepinephrine and/or dopamine (except the latest drug
esketamine, approved in 2019, a chemical derivate of the anaesthetic and

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 11

M. P. Hengartner, Evidence-biased Antidepressant Prescription,
https://doi.org/10.1007/978-3-030-82587-4_2
12 M. P. Hengartner

popular street drug ketamine, which primarily acts on NMDA receptors

[94]). The first-generation antidepressant drugs, the MAOIs and the tri-
cyclics, were discovered in the late 1950s and introduced in clinical prac-
tice around 1960 [1, 95]. The SSRIs, SNRIs, and the atypicals form the
broad class of new-generation antidepressants (sometimes SSRIs are also
referred to as second-generation and SNRIs and atypicals as third-gener-
ation antidepressants). The SSRIs were introduced in the late 1980s and
early 1990s and most SNRIs in the late 1990s and 2000s. The atypical
antidepressants were introduced at various periods. Some entered the
market in the 1980s and 1990s (for example bupropion and mirtazap-
ine), and others only recently in the 2010s (for example vilazodone and
vortioxetine). The generic and brand names of the most popular drugs
from each class in the treatment of depression still on the market are
shown in Table 2.1.
Most antidepressants were first approved for the treatment of depres-
sive disorders and still are mostly prescribed for that condition [96-99].
Between the 1960s and 1980s, the MAOIs and tricyclics were predomi-
nantly prescribed by psychiatrists in psychiatric hospitals to patients with
severe (melancholic) depression. With the advent of the SSRIs, which
were safer in overdose and easy to use (achieving the optimal dose), anti-
depressants were increasingly prescribed in primary care by GPs for less
severe forms of depression and for tension, stress symptoms, and anxiety
[63, 93, 95]. Since the late 1990s, antidepressants also became popular
treatments for anxiety disorders, sleep problems, and various non-­
psychiatric conditions, including pain disorders and menopause symp-
toms [96-100]. In the following I will explain in more detail how
antidepressant prescribing for depression changed over time and then I
will outline the issues of efficacy/effectiveness and the benefit–harm bal-
ance of antidepressants in depression.

Antidepressant Prescribing
The introduction of the SSRIs in the late 1980s led to a massive increase
in antidepressant prescribing. In 1980, Americans filled about 30 million
antidepressant prescriptions, in 2001 that number rose to a staggering
 2 Antidepressants in Clinical Practice 13

Table 2.1 Popular antidepressants for the treatment of depression still on

the market
Class Generic Name Brand Name
MAOIs Isocarboxazid Marplan
Phenelzine Nardil
Tranylcypromine Parnate
Tricyclics Amitriptyline Elavil
Clomipramine Anafranil
Doxepin Sinequan
Imipramine Tofranil
Nortriptyline Aventyl
SSRIs Citalopram Celexa
Escitalopram Lexapro
Fluoxetine Prozac
Paroxetine Paxil, Seroxat
Sertraline Zoloft
SNRIs Desvenlafaxine Pristiq
Duloxetine Cymbalta
Levomilnacipran Fetzima
Venlafaxine Effexor
Atypicals Agomelatine Valdoxan
Bupropion Wellbutrin
Esketamine Spravato
Mirtazapine Remeron
Trazodone Trittico, Desyrel
Vilazodone Viibryd
Vortioxetine Trintellix

264 million prescriptions, making antidepressants the best-selling drug

class of all [30]. At its peak in 1998, Eli Lilly’s SSRI fluoxetine produced
$2.8 billion in revenues [101]. In 1999, 3 of the top 10 best-selling phar-
maceuticals in the US were SSRIs—fluoxetine, paroxetine, and sertra-
line—accounting for combined revenues of $6.7 billion [24]. Over time,
newer antidepressants replaced them as market leaders. In 2006, the
SNRI venlafaxine was the number 1 antidepressant and ranked 6th best-­
selling drug in the US with $2.3 billion in revenues and the SSRI escita-
lopram was number 10 with $2.1 billion in revenues (sertraline was
number 15 with $1.8 billion in revenues) [102].
Due to their great popularity among both physicians and the public,
antidepressants have largely replaced non-pharmacological interventions
as first-line depression treatment. From 1987 to 1997, the proportion of
14 M. P. Hengartner

US outpatients with depression who were treated with antidepressants

increased from 37% to 75%, while the proportion who received psycho-
therapy declined from 71% to 60% [103]. The proportion of outpatients
receiving antidepressants remained constant at 75% from 1998 to 2007,
but the proportion of outpatients receiving psychotherapy continued to
decline and in 2007, a mere 43% of US outpatients with depression were
treated with psychotherapy, often in combination with antidepressants
[104]. Finally, in 2012/2013, a total 87% of US outpatients treated for
depression were using antidepressants as compared to 23% receiving psy-
chotherapy, of which the vast majority (79%) was additionally treated
with antidepressants [105].
During the 1990s and 2000s, antidepressant prescription rates multi-
plied not only in the US [106, 107], but in all high-income countries,
including European countries, New Zealand, and Australia [108-110].
For instance, in the UK adult population, antidepressant use increased
from about 2–3% in the mid-1980s [111] to about 6% in 1995 and
further to 13% in 2011 [112]. The most recent estimates from England
indicate that in 2017/2018, in total 17% of the adult population used an
antidepressant [113]. Most importantly, the majority of antidepressants
are now prescribed for mild, minor and subthreshold depression [105,
114], which are the most prevalent forms of depression in the general
population and in primary care [105, 115-117].
In most high-income countries, including the US, Australia, UK,
Denmark, Sweden, and Germany, for about 15 years antidepressant use
has also increased steadily in youth [118-121]. For instance, according to
a population-based study from Sweden, 2.1% of female and 1.3% of
male adolescents aged 12–17 years were on antidepressants in the year
2013, as compared to 1.1% and 0.6%, respectively, in 2006 [122]. In the
UK, 3.2% of the youth population aged 15–19 was prescribed an antide-
pressant in 2012, as compared to 2.3% in 2006, whereas in the US the
corresponding rates were 6.2% and 5.4%, respectively. Noteworthy is the
marked discrepancy between countries: in Germany the rates were only
1.4% (2012) and 0.8% (2006), thus also increasing but many times
lower than in the US [118].
In the last two decades, the rise in antidepressant prescribing was
mostly due to increasing long-term use [112, 123-125]. In the US, from
 2 Antidepressants in Clinical Practice 15

2011 to 2014, 68% of antidepressant users aged 12 years and older had
been taking the drugs for at least two 2 years, and about 25% had been
taking the drugs for 10 years and more [107]. According to Mojtabai and
Olfson [124], 7% of the US adult population had been on antidepres-
sants for at least 2 years in the year 2009/2010, as compared to 3% in the
year 1999/2000. In a large general practice study from the Netherlands,
in the period 2005–2015, 44% of antidepressant users had been taking
the drugs for 15 months and longer, as compared to 30% in the period
1995–2005 [126]. Finally, in England, as of 2018, altogether 52% of
antidepressant users had been on the drugs continuously for more than
12 months [113], and according to a large general practice study in
Scotland, 47% of adult antidepressant users were on the same drug for at
least 2 years [127].
A third prescription trend that is worth mentioning is the growing rate
of psychotropic polypharmacy. That is, antidepressants are increasingly
prescribed in combination with other psychiatric drugs. In US psychiat-
ric outpatient practice, from 1996 to 2006, 23% of adult antidepressant
users were additionally prescribed sedative-hypnotic drugs (mostly ben-
zodiazepines and Z-drugs), 13% were co-medicated with antipsychotics,
and further 13% with a second antidepressant. The rate of polypharmacy
had significantly increased from 1996 to 2006 [128]. Polypharmacy has
also increased in youths. For example, in the Swedish population aged
12–17 years, polypharmacy in antidepressant users increased from 49%
in 2006 to 70% in 2013. For the vast majority of youths using antide-
pressants, polypharmacy comprised co-medication with sedative-­
hypnotics and, considerably less so, with antipsychotics [122].
In sum, not only is an increasing proportion of the population pre-
scribed antidepressants each year, people on antidepressants also use the
drugs continuously for an ever-growing period and are increasingly co-­
medicated with other psychotropic drugs, especially sedative-hypnotics.
Although antidepressants are increasingly prescribed for anxiety, insom-
nia, and non-psychiatric conditions (e.g. pain), another consistent find-
ing is that, across countries and age groups, by far the most frequent
treatment indication is still depression [96-99, 129-131].
Another random document with
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Sergeant Montgomery, of the prison. Brock made no effort to secure
counsel, or to summon any witnesses, but merely expressed a
desire to have his uncle sell his land, a tract of two hundred acres
owned by him in Coffee County, Ala., and turn the proceeds over to
his mother.
On the 16th of October, by appointment, the U. S. District
Attorney, A. M. Lea, Col. J. H. Neville, Special Counsel employed by
the Government to assist in the trial, and the express officials, who
were familiar with the facts, all met at Jackson, Miss., to arrange for
the approaching trial of L. C. Brock and Rube Smith. All of these
gentlemen called in company upon Brock, in his cell at the
penitentiary, and District Attorney Lea told Brock if he had any
witnesses he desired summoned he would have subpœnas issued,
and that he was free to choose as to whether he would plead guilty
or employ counsel. Brock then and there reiterated his determination
to plead guilty, so frequently made prior to that time to the author,
and said he had no money, and did not intend to employ any
counsel. He said he was willing to testify against Smith, but
remarked:
“What will people think of me for doing that—see how the world
looks upon Bob Ford?”
When told that all fair-minded and Christian people would
applaud him for standing on the side of honesty and truth, he added:
“Well, the Bible does not give Judas Iscariot a very fair name.”
And so it was easily discovered that the ill-fated criminal was
battling against opposing ideas. On the one hand he was confronted
with the certainty of conviction and an ignominious death at the
hands of the hangman, on the other life imprisonment, with the
added alternative of standing as a witness against his copartner in
crime and assisting to fasten guilt upon him. He had often said:
“I prefer death to imprisonment for life, for what is life without
liberty.”
On Saturday, the 8th of November, two days before his suicide,
he said to a fellow prisoner, whose hat was worn and old:
 “You need a new hat; you may have mine Monday.”
Brock had evidently made up his mind, as indicated by these
remarks, to take his own life. About nine o’clock on the morning of
November 10, 1890, the day set for his trial, Detective Thomas
Jackson and United States Marshal Mathews went to the
penitentiary building to bring the prisoner to the Federal Court, as he
had been notified would be done. Sergeant Montgomery sent the
officer of the prison charged with the special surveillance of Brock to
bring him into his office, where the detective and marshal awaited
him. At night he was confined in one of the cells on the ground floor
of the prison, but was permitted to occupy during the day one of the
guard rooms situated on the third floor of the building. The prisoner
was in this room when the keeper went after him to bring him to the
sergeant’s office. Just as the keeper was in the act of unlocking the
door, Brock walked to the iron barred window of the room, and
beckoning to a fellow convict standing in the yard of the prison, threw
out of the window the following note:

November 10th, 1890.

To all who may read this, I write this to inform you that my
name is L. C. Brock; was born and raised in Coffee county,
southeast Ala. and I am not guilty of the crime for which I am
imprisoned. I am innocent, the God of Heaven knows it. I have
suffered all the while for the crime of some one else. On the 29th
of September I wrote to L. B. Moseley, Deputy U. S. Marshal,
Jackson Miss. to come and get the names of my witnesses. he
has not come yet. I do not believe the letter was mailed to him at
all. through August I had fever and nothing to lay on up stairs
(daytime) but the floor, fainted 25 or 35 times from weakness. I
am telling this to show or give you an idea of how I have been
treated. They entend to force me to a trial without my witnesses.
You show this to any and all if you wish.
Respectfully,
L. C. Brock.
 The officer, unlocking the room door, announced that he had
come to take him to the sergeant’s office, where the marshal and
Detective Jackson were in waiting to take him to the courtroom. “All
right,” said Brock, and immediately followed the officer out.
The penitentiary cells are four deep, one above the other, around
a large corridor, eighty feet long, making an open court sixty feet
deep. When the prisoner reached the head of the stair-way, in front
of the door of his room, instead of descending with the officer he
turned down the hall-way and commenced to ascend the stair-way
leading to the fourth floor. At the same time he drew a murderous
looking knife, which he had secured and secreted in some
unaccountable manner, and bade the guard stand back or he would
cut him. Sergeant Montgomery was at once notified of the unusual
conduct of the prisoner, and, in company with Detective Jackson and
Marshal Mathews, immediately repaired to the rotunda of the court
and inquired of the prisoner what he meant by such conduct. Brock
was then calmly walking to and fro along the floor of the fourth story
brandishing his knife, and at once declared his intention to jump to
the ground beneath and kill himself. Meantime the note thrown from
the window had been handed to the officers of the prison, and Brock
was asked to name the party to whom he had given letters, asking
that witnesses be summoned. This he refused to do, but stated that
the Southern Express Company intended to “railroad” him either to
the gallows or to life imprisonment without giving him even the
shadow of a showing, whereupon Marshal Mathews assured him
that he should not go to trial without counsel, and further stated that
he would see that all the witnesses he desired should be summoned.
Brock refused to come down, and, despite the assurances and
entreaties of the officers, continued to repeat his intention to take the
fatal leap. The stern and determined expression upon the desperate
man’s face, his cool and collected demeanor, convinced all who saw
and heard him that an awful tragedy would soon be enacted.
At this juncture the prisoner placed a table near the balcony
railing, mounted it, declared he was alone and friendless in the
world, and preferred death to life imprisonment. He asked that his
uncle, Mr. Harrell—then at Jackson, although the prisoner did not
know it—be telegraphed the information of his death, and that his
body be sent to his mother.
Sergeant Montgomery, meantime, had conceived the idea of
climbing the latticed walls of the court, and while the other officers
diverted his attention, would reach the fourth story, directly under
him, and overturn the table, and before the prisoner could regain his
footing he would pinion him and prevent his suicide. Divesting
himself of coat and hat, the Sergeant climbed as far as the third
story, when he was prevailed upon not to risk his life in such a
hazardous feat, as the prisoner would undoubtedly knife him before
he could carry out his project. He then came down.
The officers vied with each other in appealing to the prisoner’s
manhood, and entreating him to forego the fatal project. Finally
Detective Jackson and Marshal Mathews noiselessly went up the
stair-way until they stood on the landing just behind and about six
feet from the prisoner, urging him all the while to put away his knife
and come down stairs. Detective Jackson, approaching within three
or four feet of the prisoner, said:
“Joe, you are not going to jump, are you?”
“Yes, I am,” replied the prisoner, and stepping from the table to
the railing, he sprang head foremost into the awful space. Vaulting
over and over in his rapid flight to the stone-covered corridor, sixty
feet below, he fell, crushed and bleeding, with a sound that
reverberated through the long tiers of cells, from which the gaping
eyes of his fellow prisoners looked, in speechless horror, upon a
tragedy so appalling as to make strong men shudder and turn pale.
The unfortunate victim of his own desperation lingered for about one
hour, unconscious, his body writhing in horrible contortions until
death ensued. He was buried in the prison cemetery at Jackson at
five o’clock on the evening of his death.
The author, having repeatedly visited Brock while confined at
Jackson, takes pleasure in acquitting the officers of the State
penitentiary of any maltreatment of the prisoner.
 The prisoner made no attempt to secure witnesses; in fact,
repeatedly stated he had none. The statement written and thrown
from the window, is, therefore, not entitled to credit. A few minutes
before his suicide he freely confessed to having received fair
treatment at the hands of the prison officials.
The following lines were found on his person after death,
indicating that the bold outlaw, in his hours of retrospection, had
garnered the bitter fruitage of despair and remorse so aptly depicted:

“How wise we are when the chance is gone,

And a glance we backward cast.
We know just the thing we should have done
When the time for doing is past.”
 CHAPTER XXII.
RUBE SMITH’S TRIAL FOR THE BUCKATUNNA MAIL
ROBBERY—AN UNSUCCESSFUL ALIBI—PERJURED
WITNESSES—MASTERLY SPEECHES—CONVICTION AND
SENTENCE.

THE tragic and appalling death of L. C. Brock, alias Joe Jackson,

while it spread consternation among his fellow prisoners and
disturbed somewhat the serenity of the Court, did not impede the
course of justice. The trial of Rube Smith for the Buckatunna mail
robbery was proceeded with in the Federal Court, Judge R. A. Hill
presiding, as though nothing had occurred. It was of but little
importance to the defendant whether he should be tried at that time
or later. He had already been convicted in the State Court for the
express robbery and sentenced to imprisonment for ten years.
His defense was conducted in a skillful and able manner by
Colonel John A. Blair, of Tupelo, Miss. The Government was
represented by Captain A. M. Lea, United States District Attorney,
who made a masterly presentation of the case in behalf of the
prosecution. Captain Lea was assisted by Col. J. H. Neville, the
brilliant Prosecuting Attorney for the Second Judicial District of
Mississippi. Col. Neville had successfully conducted the prosecution
for the express robbery, and had, on account of his familiarity with
the facts and his recognized ability, been employed by the
Department of Justice to assist in the prosecution.
The corpus delicti was proved by the introduction of the
conductor, engineer, express messenger and the railway mail agent.
Neil McAllister, a very sensible colored man, in whose cabin the
robbers spent two days immediately preceding the occurrence,
identified Rube Smith as one of the men who had occupied his
cabin, and disappeared on the morning of the robbery. W. D.
Cochran, an intelligent farmer of the vicinity, also identified Smith as
being in that locality two days before the train was robbed.
McClung’s testimony, reciting all the details of the robbery as given
him by Smith, was corroborated by the engineer and other train
employes. The letters written by Smith, his proposition to become a
witness for the prosecution against Brock, which was declined, all
formed links in the chain of testimony against him which the skill and
ability of defendant’s counsel could not weaken or break. The father
of the prisoner testified that his son had slept at his home in Lamar
County on the night of the Buckatunna robbery. James Barker and
Jasper Smith, the former an uncle by marriage, and the latter a first
cousin of the defendant, both testified unscrupulously and recklessly
in support of the alibi sought to be established.
As a fitting climax to the trial, otherwise famous as it had been
rendered by the tragic events that had so closely preceded it, James
Barker and Jasper Smith were arrested for perjury immediately on
leaving the witness stand. The Grand Jury being in session they
were indicted at once, and finding that any defense would be
useless, both entered a plea of guilty. James Barker was sentenced
to three years’ and Jasper Smith to two years’ imprisonment at hard
labor at Detroit.
Consequent upon the arrest of the defendant’s witnesses for
perjury originated a good story on Colonel Blair. Jim McClung,
Smith’s pal, had been confined in default of bond in the jail at
Jackson as a witness. When James Barker and Jasper Smith were
arrested they sent for Colonel Blair, who went to the jail to visit them.
On entering, Colonel Blair found Jim McClung playing a game of
solitaire in the hall of the jail. Jim is wholly illiterate, but was
possessed of a good deal of droll wit that made him an entertaining
witness. The following conversation ensued between Colonel Blair
and Jim McClung:
Col. B.—“Good morning, Jim. How are you this morning?”
Jim McC.—“Only tolerbul, Colonel—not feelin’ very well. How
are you?”
 Col. B.—“First rate, Jim, but I am not surprised that you are not
feeling very well. I don’t see how a man can feel very well who has
(alluding to his testimony against Smith) put his friend in prison, as
you have done.”
Jim McC.—“Well, now, Colonel, look here. Before you come into
this case there warn’t but one of my friends in prison, and now you
have been a foolin’ with the case sence last spring and you’ve got
three of ’em in. How is that? Eh?”
The joke was on the gifted and brilliant attorney. He had been
powerless to stem the tide which swept his client and witnesses alike
into the prisoner’s cell.
On the eighteenth day of November, 1890, Rube Smith was
brought before the bar of the Court by the marshal, and asked by the
venerable Judge presiding if he had anything to say as to why the
judgment of the law should not be pronounced upon him for the
crime of which he stood convicted. The prisoner replied he had
nothing further to say, whereupon Judge Hill addressed him as
follows:
“Mr. Reuben Smith, the crime of which you stand convicted, and
for which it becomes my duty as presiding Judge of the Court to
pronounce against you the penalty of the law, which is confinement
at hard labor in the penitentiary for the remainder of your natural life,
is that of forcibly and violently robbing the United States mail. This
crime is the highest crime known to the law of the United States,
save that of murder and treason, and is punished with the severest
penalty save that of death. The reason therefor is that the robber
usually engages in robbery with the determination to murder his
victims if necessary to carry out his purpose.
“It is sad to behold a young man like yourself, who, by an upright
and virtuous life, might have been an honorable and useful citizen,
enjoying the blessings of the most refined and elevated society,
banished, as it were, from all that renders life desirable. The evil
consequences of your crime are not confined to yourself. For to save
you from the punishment of your offense no less than five of your
family and friends have perjured themselves to establish an alibi in
your behalf, for which offense two of them have already pleaded
guilty and are condemned to serve terms at hard labor in the
penitentiary—a punishment the more serious in its consequences
because not confined to themselves alone, but to their helpless
families and children as well.
“Sad as these consequences are, you may, and it is your duty, to
repent of your offense against the laws of the State and the Nation,
and against your Maker, your family, and your own well-being, and
commence a new life by obeying strictly all the laws of God and
man, and especially the regulations of the prison in which you will be
confined. If you do this, in the course of time the President may grant
you a pardon; but whether this is granted or not, your best interest is
to obey whatever may be required of you, and also to employ all of
the means that may be offered you to improve your mind and your
morals, and to make preparations for the final judgment.
“I feel assured that if you conduct yourself properly you will be
not only treated well, clothed and fed well, but will receive as kind
treatment as the circumstances will permit.
“Will you promise me that you will follow this advice? (The
prisoner replied in a subdued tone, “I will follow your advice.”)
“The judgment of the Court and of the law is, that for the offense
for which you stand convicted you be delivered to the warden of the
penitentiary of the State of Ohio, at Columbus, and be there
imprisoned at hard labor for and during your natural life.”
 CHAPTER XXIII.
CONCLUSION.

“An honest tale speeds best, being plainly told.”

IF the reader has been disappointed in the fact that the hero of this
narrative has not been vested with the glamour of princely wealth;
that he has not been painted a knight-errant of more romantic type;
and that a champion in the field of pillage and plunder should not
wear golden spurs and a helmet of brass, the fault lies not with the
author, but rather with the popular error which pre-supposes these
fallacious results.
The stereotyped question of all interested in his career has been,
“What did Rube Burrow do with his money?”
The accuracy of the statement is vouched for, that in all of the
eight train robberies, from Ben Brook, Texas, to Flomaton, Ala.,
reckoning his share as equal with that of his companions in crime,
Rube Burrow secured not exceeding five thousand five hundred
dollars. He invested, in the spring of 1887, about four hundred
dollars by purchasing a one-half interest, with his brother, in a few
acres of land in Texas. Soon after the Genoa robbery he purchased
for sixteen hundred dollars the farm on which his father now resides
in Lamar County, paying four hundred dollars cash and giving his
note for twelve hundred dollars. A few weeks after the Buckatunna
robbery this note, through his father, was paid, some of the currency
used being subsequently identified as part of that stolen at
Buckatunna. The residue, the pitiful sum of three thousand five
hundred dollars, was spent in the vain endeavor to avoid the
ceaseless pursuit organized against him, and which made the latter
years of his life an intolerable burden.
 In the autumn of 1889 Rube Burrow made, through one of his
kinsmen, a proposition to the officers of the Southern Express to
surrender, upon the condition that he would not be tried for the
murder of Hughes or Graves. The proposition was, of course,
promptly declined.
L. C. Brock, alias Joe Jackson, stated, after his arrest, that he
had at one time made up his mind to seek an interview with
Detective Jackson, with a view of making some conditions for his
own surrender, but Rube’s proposition having been declined he gave
up the project.
Although lawless by instinct, training and ambition, these men
had drunk the bitter cup of crime to the dregs, and longed, no doubt,
to enfranchise themselves from the toils that beset them, and which,
like an avenging Nemesis, pursued them to the end.
The Southern Express Company expended, independently of all
rewards, about twenty thousand dollars in the hunting down of this
band of train robbers. The total rewards offered for Rube Burrow
amounted to about $3,500. The rewards of $1,000 by the United
States Government, and $250 by the State of Mississippi, have
been, so far, withheld, because the language of the statutes, both
Federal and State, under which the rewards were offered, required
conviction in the courts.
Inspector A. G. Sharp, of the United States Postal Service, who
has been very zealous in urging that the rewards offered by the
Government be paid, writes under date of December 17, 1890, as
follows:

“While in Washington recently, I laid the matter of reward for

Rube Burrow and Joe Jackson before the Postmaster-General
and the Chief Inspector, and strongly urged that the rewards for
both be paid, and the question of conviction be waived. I believe
the claims to be just, and that good policy suggests prompt
payment. I feel satisfied that the Postmaster-General will accept
my advice in the matter, and that the rewards for both will be
paid in full. Of this, however, I can not speak positively; but from
 the reply made by the Postmaster-General, to my earnest
solicitation, I feel justified in saying that I have strong reasons for
believing that he will make the order allowing the rewards.”

All other rewards for Rube Burrow have been paid to Carter and
his associates. The rewards for Brock and Smith, excepting those
offered by the Government and the State of Mississippi, have also
been paid to the parties interested.
William Brock, of Texas, was in nowise related to L. C. Brock.
The two men never met, and that two of Burrow’s clansmen bore the
same name was merely a coincidence.
The question recurs, “Does train-robbing pay?”
Here were men whose untoward inclinings, fostered by evil
association, inflamed them with a passion for lawlessness. Their
brawny arms were uplifted against the laws of God and man for
ambition’s sake. They loved pillage for booty’s sake.
Behold the hapless fate of the five men who linked their fortunes
together, commencing with the date of the Genoa robbery in
December, 1887. William Brock, although sentenced to a short term
of imprisonment, will carry to his grave the stigma of an ex-convict.
Rube Smith has entered the gloomy portals of a prison, in which he
is doomed to spend the remaining days of his life—a fate more
horrible than death.
Rube Burrow, Jim Burrow and L. C. Brock lie in unhallowed
graves, their memories kept alive only by the recollection of their
atrocious deeds, leaving their kindred and friends to realize the bitter
truth that

“The evil that men do lives after them;

The good is oft interred with their bones.”

Verily, “the way of the transgressor is hard”—“for whatsoever a

man soweth, that shall he also reap.”
 Transcriber’s Notes
Punctuation, hyphenation, and spelling were made
consistent when a predominant preference was found in the
original book; otherwise they were not changed.
Misspellings and poor punctuation in some letters have
been retained.
Simple typographical errors were corrected; unbalanced
quotation marks were remedied when the change was
obvious, and otherwise left unbalanced.
Illustrations in this eBook have been positioned between
paragraphs and outside quotations. In versions of this eBook
that support hyperlinks, the page references in the List of
Illustrations lead to the corresponding illustrations.
 *** END OF THE PROJECT GUTENBERG EBOOK RUBE
BURROW, KING OF OUTLAWS, AND HIS BAND OF TRAIN
ROBBERS ***

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