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Abstract

Antidepressant drugs are the mainstay of depression treatment in both primary and specialized mental health care. However, academic psychiatry holds false beliefs about antidepressants and we expose two of them in this essay. First, recent attitude surveys conducted among psychiatrists and general practitioners have revealed that physicians attribute antidepressants’ effects mostly to the drugs’ pharmacologic action and less so to placebo effects. Second, academic psychiatry maintains that physical dependence to antidepressant drugs does not exist and that “discontinuation symptoms” upon stopping maintenance pharmacotherapy are benign and affect only a small minority of antidepressant users. As we review in this essay, these beliefs are at odds with the scientific literature. The largest and most comprehensive meta-analysis of antidepressant trials conducted to date indicates that 88% of the drugs’ treatment outcome is accounted for by placebo effect. Furthermore, physical dependence appears to be a serious issue, as severe and persistent withdrawal reactions affect up to 50% of antidepressant users according to several studies. Correcting false beliefs prevailing in academic psychiatry is needed and has important implications for psychiatric training, continuing medical education, and practice.
Essays
False Beliefs in Academic Psychiatry:
The Case of Antidepressant Drugs
Michael P. Hengartner, PhD
Zurich University of Applied Sciences, Zurich, Switzerland
Martin Plöderl, PhD
University Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Paracelsus Medical
University, Salzburg, Austria
Antidepressant drugs are the mainstay of depression treatment in both primary and
specialized mental health care. However, academic psychiatry holds false beliefs about
antidepressants and we expose two of them in this essay. First, recent attitude surveys
conducted among psychiatrists and general practitioners have revealed that physicians
attribute antidepressants’ effects mostly to the drugs’ pharmacologic action and less so
to placebo effects. Second, academic psychiatry maintains that physical dependence to
antidepressant drugs does not exist and that “discontinuation symptoms” upon stopping
maintenance pharmacotherapy are benign and affect only a small minority of antidepres-
sant users. As we review in this essay, these beliefs are at odds with the scientific literature.
The largest and most comprehensive meta-analysis of antidepressant trials conducted to
date indicates that 88% of the drugs’ treatment outcome is accounted for by placebo effect.
Furthermore, physical dependence appears to be a serious issue, as severe and persistent
withdrawal reactions affect up to 50% of antidepressant users according to several studies.
Correcting false beliefs prevailing in academic psychiatry is needed and has important
implications for psychiatric training, continuing medical education, and practice.
Keywords: antidepressant; depression; efficacy; placebo; discontinuation; withdrawal
With the powerful support of the pharmaceutical industry, academic psychia-
try has advertised a neurobiological etiology of depression over the last three
decades (Lacasse & Leo, 2005; Read & Cain, 2013; Whitaker & Cosgrove,
2015). This close co-operation resulted in an increased public acceptance of both neu-
robiological explanations and psychopharmacological treatments (Schomerus et al.,
2012), and media portrayals of the biomedical model of depression and antidepressant
drugs as the preferred treatment have strongly increased from the 1980s to the 2000s
(Clarke & Gawley, 2009). People consume more and more antidepressants each year
(Ilyas & Moncrieff, 2012; Kantor, Rehm, Haas, Chan, & Giovannucci, 2015; Vilhelms-
son, 2013), but, unfortunately, it seems that the public did not benefit from this marked
increase of antidepressant prescriptions. Depression prevalence rates remained largely
unaltered (Jorm, Patten, Brugha, & Mojtabai, 2017), whereas the burden and disabil-
Ethical Human Psychology and Psychiatry, Volume 20, Number 1, 2018
© 2018 Springer Publishing Company
http:// dx. doi. org/ 10. 1891/ 1559- 4343. 20. 1.6
6
ity attributable to depression have even increased in the general population (OECD,
2012; Whitaker, 2005). As a consequence, for a few years psychiatry is facing grow-
ing skepticism towards the benefits of antidepressant pharmacotherapy (Antonuccio,
Danton, DeNelsky, Greenberg, & Gordon, 1999; Gotzsche, 2015; Hengartner, 2017;
Moncrieff & Kirsch, 2005). Ongoing issues include, for example, the reporting and
publication biases inflating the apparent efficacy of antidepressant drugs (Pigott, 2011;
Turner et al., 2008), the disregard of both antidepressant dependence and withdrawal
reactions (Fava, Gatti, Belaise, Guidi, & Offidani, 2015; Nielsen, Hansen, & Gøtzsche,
2012), and the dismissal of patient reports of drug-induced adverse events (Gibson,
Cartwright, & Read, 2014; Medawar, Herxheimer, Bell, & Jofre, 2002).
A remarkable example is provided by the conclusion of leading European psychia-
trists to their own survey on patients’ attitudes towards antidepressants (Kessing, Han-
sen, Demyttenaere, & Bech, 2005). According to this work, 57% of antidepressant
users agreed that it is difficult to stop antidepressants when you have taken them over a
long period of time, and 56% agreed that your body can become addicted to antidepres-
sants. Instead of taking these concerns seriously, the authors stated that a large portion
of patients have erroneous views and lack knowledge about antidepressant pharmaco-
therapy. This conclusion is disrespectful of the patients’ lived experiences. Given that
the study was published in a leading scientific journal, this also raises serious concerns
about the adequacy of the peer review and, accordingly, the views of both editors and
reviewers. The study was published in 2005, at a time when leading psychiatrists should
have known that stopping or interrupting antidepressant pharmacotherapy causes drug-
induced withdrawal symptoms (e.g., Michelson et al., 2000; Rosenbaum et al., 1998).
A more recent illustration was provided by the launch of the Council for Evidence-
Based Psychiatry (CEP) in April 2014. CEP was initiated to communicate evidence of
the potentially harmful effects of psychiatric drugs to the public. In an interview with The
Times, CEP cofounder Professor Peter Gotzsche detailed why he thinks that antidepres-
sants do more harm than good (see https://www. thetimes. co. uk/ article/ antidepressants-
do- more- harm- than- good- research- says- 80p8njbcxbd). This press release stirred a fierce
reaction from leading British psychiatrists published in The Lancet Psychiatry, where they
accused Professor Gotzsche of “irrational polemic” and “flawed statements” (Nutt, Good-
win, Bhugra, Fazel, & Lawrie, 2014). But is there really such compelling scientific evi-
dence to discount critical views as irrational and flawed? Considering the scientific flaws,
methodological biases, and conflicts of interest in mostly industry-sponsored antidepres-
sant trials (Melander, Ahlqvist-Rastad, Meijer, & Beermann, 2003; Moncrieff & Kirsch,
2005; Perlis et al., 2005; Turner et al., 2008), there certainly is good reason to question
the alleged benefits of antidepressants (Antonuccio et al., 1999; Hengartner, 2017; Pigott
et al., 2010).
Obviously, there is a heated debate about the merits of antidepressants, where academic
psychiatry defends its favorable position on antidepressants by discrediting critical views
as erroneous and unsubstantiated (see also Whitaker & Cosgrove, 2015, for a detailed
account of the underlying institutional corruption). As we will suggest in this essay, the
problem is presumably less with erroneous views expressed by patients and researchers
critical of psychopharmacological drugs, but rather with false beliefs held by academic psy-
chiatry and promoted by the pharmaceutical industry. To not further divide proponents
and opponents, we would like to stress that our critical reappraisal of antidepressant drugs
is not intended as a stigmatizing campaign against psychiatry, as, for instance, claimed
7False Beliefs in Academic Psychiatry
by Nutt et al. (2014), but as a sincere attempt to counter criticism against patients and
researchers who express opposing views. As long as drug-critical findings are dismissed as
false presumptions made by uninformed patients or conspiring antipsychiatrist movements
(see Nutt et al., 2014), there is no possibility to improve the acceptance and care of people
with severe mental health problems.
PHARMACOLOGICAL DRUG EFFECTS ARE OVERSTATED
Physicians substantially overestimate the pharmacological effects of antidepressants and
their benefits overall. For instance, in a recent attitude survey conducted at an academic
hospital in the United States, the 79 surveyed psychiatrists indicated that only 26%
of antidepressants’ effectiveness was due to placebo effects (Vijapura, Laferton, Mintz,
Kaptchuk, & Wolfe, 2016). In another recent attitude survey among 87 German physi-
cians (of whom 40% were psychiatrists), approximately 60% of a drug’s total effectiveness
was attributed to its pharmacologic action and 40% to placebo effects (Kampermann,
Nestoriuc, & Shedden-Mora, 2017). These beliefs contrast with the results of randomized
placebo-controlled trials (for a recent meta-analysis, see Cipriani et al., 2018), which sug-
gest that 88% of antidepressants’ short-term efficacy is attributable to placebo effects, and
only 12% to their pharmacologic action.1 For the sake of simplicity, we consider spontane-
ous remission some kind of placebo effect, but note that formally spontaneous remission
would fall under the concept of placebo response. That is, approximately 8–10 people
need to undergo antidepressant pharmacotherapy in order for one person to benefit from
such treatment relative to placebo (McCormack & Korownyk, 2018). Research further
suggests that this small effect size is inflated due to conflicts of interest and method biases
and that it is clinically insignificant in routine practice (Gotzsche, 2015; Hengartner,
2017; Moncrieff & Kirsch, 2005; Pigott et al., 2010). That is, psychiatrists substantially
overestimate a drug’s pharmacologic effect, and they clearly underestimate the importance
of placebo effects (Vijapura et al., 2016).
Moreover, 93% of physicians agree that efficacy is due to a drug’s pharmacological
effect, but only 81% agree that side effects are caused by pharmacological effects (Kam-
permann et al., 2017), suggesting that a drug’s desirable effect (efficacy) is more frequently
attributed to its pharmacologic action than a drug’s adverse effects. This is another false
belief given that drug–placebo differences are much larger for adverse events (risk ratio
for decreased libido, tremor, and nausea is 3.5, 3.2, and 2.5, respectively) than for efficacy
estimates (risk ratio for both response and remission is 1.4) in meta-analyses of randomized
controlled trials (Jakobsen et al., 2017). Such findings do not necessarily prove that the
risks outweigh a drug’s benefits, because patients might accept to endure adverse effects
such as nausea or sexual dysfunction even when the reduction of depression symptoms is
modest. However, it seems that patients do not consider the drugs to be helpful, as they
prematurely terminate treatment with antidepressants at the same rate as treatment with
inert placebo (Arroll et al., 2009; Cipriani et al., 2018). Thus, based on patients’ behavior,
the benefits likely do not outweigh the risks. Given that the effect size for sexual dysfunc-
tion is much larger than the drugs’ antidepressant action, others have argued that a more
accurate label for antidepressants would be “antiaphrodisiac medications” or “antisexual-
ity drugs” (Antonuccio & Healy, 2012; Gotzsche, 2015).
8Hengartner and Plöderl
Interestingly, the longer the time since graduation, the stronger psychiatrists believe in
a drug’s pharmacologic action and the smaller they perceive the importance of placebo
effects (Vijapura et al., 2016). These findings suggest that more experienced psychiatrists
(who more frequently are both in leading positions and members of expert groups) are less
considerate of the more recent developments in the scientific literature on antidepressants’
efficacy. In addition, although 96% of psychiatrists were familiar with the recent literature
questioning the efficacy of antidepressants, only 23% reported that these studies have
influenced their prescribing practices (Vijapura et al., 2016). These findings further raise
the issue why continuing medical education has not resulted in a more evidence-based
appreciation of placebo effects, given that meta-analyses have already shown at the turn of
the 21st century that the response to placebo accounts for at least 80% of antidepressants’
efficacy (Kirsch, Moore, Scoboria, & Nicholls, 2002). This finding, which corresponds to
an effect size of approximately d = 0.3, was replicated many times since by independent
research groups (e.g., Jakobsen et al., 2017; Rabinowitz et al., 2016; Turner et al., 2008)
and must be considered best available evidence. To be clear, we do not contend that
antidepressant drugs have no mental effects at all. Antidepressants are psychoactive drugs
that may alter mental functioning (Moncrieff & Cohen, 2006), the most common effects
including emotional numbing, depersonalization, drowsiness, and agitation (Goldsmith
& Moncrieff, 2011; Read, Cartwright, & Gibson, 2014). However, we contend that they
do not specifically treat depression symptoms, as their antidepressive action is poor and
clinically insignificant (Gotzsche, 2015; Hengartner, 2017; Moncrieff & Kirsch, 2005;
Pigott et al., 2010).
SEVERE WITHDRAWAL EFFECTS ARE NEGLECTED
Another important discrepancy between the scientific literature and prevailing beliefs
held among leading psychiatrists concerns physical dependence and withdrawal symptoms
upon discontinuation of antidepressant medication. Although withdrawal is a bothersome
problem for many long-term users, the issue is largely neglected in the scientific literature,
in routine practice, and in psychiatric training (Fava et al., 2015; Gotzsche, 2015; Nielsen
et al., 2012). It is not uncommon for patients who report antidepressant withdrawal symp-
toms to be dismissively told by their physicians that these symptoms have nothing to
do with the drugs, but rather are signs of their underlying mental health problem (Gib-
son et al., 2014; Medawar et al., 2002). Kessing et al. (2005) even stated that patients
experiencing difficulties in stopping antidepressants due to physical dependence have
erroneous beliefs about the drugs. Recently, 30 people, including patients, scientists, and
practitioners, lodged a formal complaint with the Royal College of Psychiatrists (RCP)
for misleading the public on antidepressant withdrawal and for burying inconvenient data
from their own research program (see http:// cepuk. org/ 2018/ 03/ 09/ patients- academics-
psychiatrists- formally- complain- president- royal- college- psychiatrists- misled- public- anti-
depressant- safety/). This complaint was a response to a letter in The Times published on
February 24, 2018, where RCP president, Professor Wendy Burn, and the RCP chair of
the psychopharmacology committee, Professor David Baldwin, stated that “[for] the vast
majority of patients, any unpleasant symptoms experienced on discontinuing antidepres-
sants have resolved within two weeks of stopping treatment.” Such claims have been made
9False Beliefs in Academic Psychiatry
before by many others (e.g., Haddad, Lejoyeux, & Young, 1998), despite a clear lack of
supporting evidence.
Research consistently shows that bothersome withdrawal symptoms, including mood
instability, irritability, brain zaps, dizziness, or fatigue, occur in up to 50% of all patients
upon both abrupt and slow discontinuation (Fava, Bernardi, Tomba, & Rafanelli, 2007;
Rosenbaum et al., 1998; Sir et al., 2005; for a systematic review, see Fava et al., 2015). In a
recent survey among almost 1,200 long-term antidepressant users, 62% had unsuccessfully
attempted drug tapering before. Of these, 97% experienced withdrawal, with 49% report-
ing severe withdrawal (Groot & van Os, 2018). In a comprehensive attitude survey con-
ducted among over 1,800 antidepressant users in New Zealand, between 12% (fluoxetine)
and 47% (paroxetine) of respondents reported severe withdrawal effects (Read et al.,
2014). A randomized double-blind placebo-substitution trial showed that 6% (fluoxetine),
30% (sertraline), and 36% (paroxetine) of patients with remitted depression experienced
substantial increases in depression symptoms within 5–8 days of treatment interruption.
Due to fluoxetine’s long elimination half-life, 5–8 days interruption is too short a period of
time for withdrawal symptoms to emerge (Chouinard & Chouinard, 2015). The results for
fluoxetine must therefore be interpreted with caution. According to another randomized
trial, 34% (sertraline) and 44% (venlafaxine XR) of patients develop moderate to very
severe discontinuation symptoms following drug taper (Sir et al., 2005). Finally, in a meta-
analysis of placebo-controlled, mostly short-term duloxetine trials, 54.9% of withdrawal
syndromes lasted longer than 2 weeks (Perahia, Kajdasz, Desaiah, & Haddad, 2005).
For a significant minority, withdrawal reactions are severe to an extent that the symp-
toms qualify for a drug-induced persistent postwithdrawal affective disorder (Belaise, Gatti,
Chouinard, & Chouinard, 2012; Chouinard & Chouinard, 2015). In the double-blind
placebo-controlled trial by Rosenbaum et al. (1998) in patients with remitted depression,
withdrawal reactions qualified as depression relapse in up to 27% of patients, and in the
naturalistic observational study by Fava et al. (2007), 15% of patients with remitted panic
disorder with agoraphobia developed a cyclothymic disorder after gradual antidepressant
discontinuation. It has yet to be clearly established for how long severe withdrawal syn-
dromes and drug-induced affective disorders persist, but available data clearly show that
the problem is much more serious than academic psychiatry is willing to admit. That is,
bothersome withdrawal reactions are quite common and there is no evidence that these
symptoms dissipate within 2 weeks in the vast majority of persons concerned (Fava et al.,
2015). Antidepressant withdrawal, therefore, is a serious public health issue that warrants
more research and adequate appraisal by academic psychiatry (Gotzsche, 2015).
THE PAST, THE PRESENT, AND THE FUTURE
As touched on above, many antidepressant users report that they feel addicted to the drugs
(Kessing et al., 2005; Read et al., 2014), and it has been shown that, phenomenologically
and conceptually, antidepressant dependence is almost indistinguishable from benzodi-
azepine dependence (Nielsen et al., 2012). As a reminder, for almost 20 years and until
the 1980s, academic psychiatry had firmly dismissed the idea that therapeutic doses of
benzodiazepines could cause dependence (Lader, 1991). Now, leading experts suggest that
benzodiazepines are more harmful than recreational drugs such as amphetamine, tobacco,
10 Hengartner and Plöderl
cannabis, LSD, or ecstasy (Nutt, King, Saulsbury, & Blakemore, 2007). The beliefs that
there is no physical dependence to antidepressants and that “discontinuation reactions”
are a minor problem that is easy to manage (Haddad et al., 1998), are a major medi-
cal concern, since so many patients seriously suffer from antidepressant withdrawal for
months and even years (Belaise et al., 2012; Fava et al., 2015). In view of the pervasive
disregard of antidepressant withdrawal by academic psychiatry, perhaps other professionals
must assume responsibility to help the many people worldwide who suffer from physical
dependence to antidepressants. For instance, in their letter to the New York Times, science
journalists Carey and Gebeloff (2018) provide a thorough overview of the withdrawal lit-
erature, enriched with statements from withdrawal experts and some case reports, showing
that many patients do not succeed in tapering off their drugs. Although academic psychia-
try still maintains that serious problems with stopping antidepressants affect only a very
small minority, after a careful examination of the database, Carey and Gebeloff (2018)
conclude that withdrawal is a serious problem that affects many long-term antidepressant
users who want to stop their medication.
We can only speculate about why antidepressant benefits are overstated while risks,
including withdrawal reactions, are persistently minimized in academic psychiatry. One
likely reason is that academic psychiatry (Fava, 2007; Whitaker & Cosgrove, 2015) and
medicine in general (Angell, 2000; Light, Lexchin, & Darrow, 2013) are unduly influ-
enced by the commercial interests of the pharmaceutical industry. The companies produc-
ing medical drugs not only have strong financial ties with academic departments and their
leaders (Anderson, Dave, Good, & Gellad, 2014; Campbell et al., 2007) but they also
have a profound influence on the content of medical journals (Lexchin & Light, 2006;
Smith, 2005). That is, research sponsored by pharmaceutical companies is more likely
to yield both positive results and favorable conclusions (Als-Nielsen, Chen, Gluud, &
Kjaergard, 2003; Lexchin, Bero, Djulbegovic, & Clark, 2003; Lundh, Sismondo, Lexchin,
Busuioc, & Bero, 2012). These problems concern not only medicine in general, but of
course also research on antidepressant drugs. The pharmaceutical industry systematically
inflates efficacy estimates through selective reporting and publication (Melander et al.,
2003; Turner et al., 2008) and underreports adverse events and harm (de Vries, Roest,
Beijers, Turner, & de Jonge, 2016; Ebrahim, Bance, Athale, Malachowski, & Ioannidis,
2016; Maund et al., 2014).
The medical profession, supported by the pharmaceutical industry, has long denied
benzodiazepine dependence, and the same seems to happen now with antidepressant
drugs (Gotzsche, 2015; Nielsen et al., 2012). The neglect of both placebo effects and
withdrawal reactions may be largely driven by the commercial interests of the phar-
maceutical industry. Therefore, more governmentally sponsored studies conducted by
independent researchers without financial conflicts of interest related to the industry
are needed. Moreover, psychiatric training and continuing medical education should
not be sponsored, or otherwise influenced, by the pharmaceutical industry (Fava, 2007).
Finally, it is worth noting that there are other economies of influence corrupting aca-
demic psychiatry, such as, for instance, the field’s adoption of the biomedical model
of mental disorders and the promulgation of pharmacotherapy as first-line treatment
option (Whitaker & Cosgrove, 2015). Such undue influences are only bypassed when
nonmedical mental health experts, such as nurses, psychologists, or social workers, are
allowed to participate in expert committees and to have a determining influence on
practice guidelines.
11False Beliefs in Academic Psychiatry
SUMMARY AND CONCLUSIONS
In this essay, we put forward that academic psychiatry maintains two false beliefs that
have far-reaching implications for the treatment of major depression. The first belief
implies that the efficacy of antidepressants is principally due to the drugs’ pharmaco-
logic action. However, the results of large meta-analyses have consistently shown that
almost 90% of a drug’s action is due to placebo effects and, hence, that their clinical
effectiveness is questionable (Hengartner, 2017; Moncrieff & Kirsch, 2005). The sec-
ond belief maintains that physical dependence to antidepressants does not exist and
that bothersome withdrawal reactions upon treatment discontinuation affect only a
small minority of patients for a very short time. However, studies have shown that
antidepressants can cause physical dependence (Nielsen et al., 2012). Furthermore,
severe withdrawal reactions occur in up to half of all users and in long-term users these
problems can be so persistent and serious that they qualify for withdrawal-induced
affective disorders (Fava et al., 2015).
We therefore contend that some of the most insistently held beliefs in academic psy-
chiatry clearly conflict with the scientific literature. This likely has a major impact on
current treatment practice with its strong reliance on antidepressant pharmacotherapy.
Only when the field acknowledges that the drugs’ efficacy in attenuating depression
symptoms is by and large a placebo response will alternative interventions such as psy-
chotherapy or exercise be recommended to patients more often as first-line treatment.
And only when the field acknowledges that long-term antidepressant use can cause
physical dependence and severe withdrawal reactions in many, if not most patients,
then there will be fewer prescriptions for often unnecessary long-term maintenance
pharmacotherapy. Academic psychiatry remains devoted to ethical principles such as
“first do no harm,” which is why we are confident that it eventually acknowledges the
arguments outlined in this essay.
NOTE
1. The recent meta-analysis by Cipriani et al. (2018), which is the largest and most
comprehensive to date, estimated the mean effect size to be d = 0.3. This indicates that
continuous depression scores overlap by 88% between drug and placebo group.
REFERENCES
Als-Nielsen, B., Chen, W., Gluud, C., & Kjaergard, L. L. (2003). Association of funding and con-
clusions in randomized drug trials: A reflection of treatment effect or adverse events? JAMA,
290(7), 921–928. http:// dx. doi. org/ 10. 1001/ jama. 290. 7. 921
Anderson, T. S., Dave, S., Good, C. B., & Gellad, W. F. (2014). Academic medical center leader-
ship on pharmaceutical company boards of directors. JAMA, 311(13), 1353–1355. http:// dx.
doi. org/ 10. 1001/ jama. 2013. 284925
Angell, M. (2000). Is academic medicine for sale? New England Journal of Medicine, 342(20), 1516–
1518. http:// dx. doi. org/ 10. 1056/ NEJM200005183422009
12 Hengartner and Plöderl
Antonuccio, D., & Healy, D. (2012). Relabeling the medications we call antidepressants. Scientifica,
2012, 965908–6. http:// dx. doi. org/ 10. 6064/ 2012/ 965908
Antonuccio, D. O., Danton, W. G., DeNelsky, G. Y., Greenberg, R. P., & Gordon, J. S. (1999).
Raising questions about antidepressants. Psychotherapy and Psychosomatics, 68(1), 3–14. http://
dx. doi. org/ 10. 1159/ 000012304
Arroll, B., Elley, C. R., Fishman, T., Goodyear-Smith, F. A., Kenealy, T., Blashki, G., . . . Cochrane
Common Mental Disorders Group, Macgillivray, S. (2009). Antidepressants versus placebo for
depression in primary care. Cochrane Database of Systematic Reviews, 63(6), CD007954. http://
dx. doi. org/ 10. 1002/ 14651858. CD007954
Belaise, C., Gatti, A., Chouinard, V. A., & Chouinard, G. (2012). Patient online report of selective
serotonin reuptake inhibitor-induced persistent postwithdrawal anxiety and mood disorders.
Psychotherapy and Psychosomatics, 81(6), 386–388. http:// dx. doi. org/ 10. 1159/ 000341178
Campbell, E. G., Weissman, J. S., Ehringhaus, S., Rao, S. R., Moy, B., Feibelmann, S., & Goold, S.
D. (2007). Institutional academic industry relationships. JAMA, 298(15), 1779–1786. http://
dx. doi. org/ 10. 1001/ jama. 298. 15. 1779
Carey, B., & Gebeloff, B. (2018). Many people taking antidepressants discover they cannot quit.
New York Times. https://www. nytimes. com/ 2018/ 04/ 07/ health/ antidepressants- withdrawal-
prozac- cymbalta. html.
Chouinard, G., & Chouinard, V. A. (2015). New classification of selective serotonin reuptake
inhibitor withdrawal. Psychotherapy and Psychosomatics, 84(2), 63–71. http:// dx. doi. org/ 10.
1159/ 000371865
Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., . . . Ged-
des, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the
acute treatment of adults with major depressive disorder: A systematic review and net-
work meta-analysis. The Lancet, 391(10128), 1357–1366. http:// dx. doi. org/ 10. 1016/ S0140-
6736(17)32802-7
Clarke, J., & Gawley, A. (2009). The triumph of pharmaceuticals: the portrayal of depression from
1980 to 2005. Administration and Policy in Mental Health and Mental Health Services Research,
36(2), 91–101. http:// dx. doi. org/ 10. 1007/ s10488- 008- 0199-2
de Vries, Y. A., Roest, A. M., Beijers, L., Turner, E. H., & de Jonge, P. (2016). Bias in the report-
ing of harms in clinical trials of second-generation antidepressants for depression and anxiety:
A meta-analysis. European Neuropsychopharmacology, 26(11), 1752–1759. http:// dx. doi. org/ 10.
1016/ j. euroneuro. 2016. 09. 370
Ebrahim, S., Bance, S., Athale, A., Malachowski, C., & Ioannidis, J. P. (2016). Meta-analyses with
industry involvement are massively published and report no caveats for antidepressants. Journal
of Clinical Epidemiology, 70, 155–163. http:// dx. doi. org/ 10. 1016/ j. jclinepi. 2015. 08. 021
Fava, G. A. (2007). Financial conflicts of interest in psychiatry. World Psychiatry: Official Journal of
the World Psychiatric Association, 6(1), 19–24.
Fava, G. A., Bernardi, M., Tomba, E., & Rafanelli, C. (2007). Effects of gradual discontinuation
of selective serotonin reuptake inhibitors in panic disorder with agoraphobia. The Inter-
national Journal of Neuropsychopharmacology, 10(6), 835–838. http:// dx. doi. org/ 10. 1017/
S1461145706007462
Fava, G. A., Gatti, A., Belaise, C., Guidi, J., & Offidani, E. (2015). Withdrawal symptoms after
selective serotonin reuptake inhibitor discontinuation: A systematic review. Psychotherapy and
Psychosomatics, 84(2), 72–81. http:// dx. doi. org/ 10. 1159/ 000370338
Gibson, K., Cartwright, C., & Read, J. (2014). Patient-centered perspectives on antidepressant use:
A narrative review. International Journal of Mental Health, 43(1), 81–99.
Goldsmith, L., & Moncrieff, J. (2011). The psychoactive effects of antidepressants and their
association with suicidality. Current Drug Safety, 6(2), 115–121. http:// dx. doi. org/ 10. 2174/
157488611795684622
Gotzsche, P. C. (2015). Deadly psychiatry and organised denial. Copenhagen, Denmark: People’s Press.
13False Beliefs in Academic Psychiatry
Groot, P. C., & van Os, J. (2018). Antidepressant tapering strips to help people come off medica-
tion more safely. Psychosis, 10(2), 142–145. http:// dx. doi. org/ 10. 1080/ 17522439. 2018. 1469163
Haddad, P., Lejoyeux, M., & Young, A. (1998). Antidepressant discontinuation reactions. BMJ,
316(7138), 1105–1106. http:// dx. doi. org/ 10. 1136/ bmj. 316. 7138. 1105
Hengartner, M. P. (2017). Methodological flaws, conflicts of interest, and Scientific fallacies: Impli-
cations for the evaluation of antidepressants’ efficacy and harm. Frontiers in Psychiatry, 8, 275.
http:// dx. doi. org/ 10. 3389/ fpsyt. 2017. 00275
Ilyas, S., & Moncrieff, J. (2012). Trends in prescriptions and costs of drugs for mental disorders in
England, 1998-2010. British Journal of Psychiatry, 200(5), 393–398. http:// dx. doi. org/ 10. 1192/
bjp. bp. 111. 104257
Jakobsen, J. C., Katakam, K. K., Schou, A., Hellmuth, S. G., Stallknecht, S. E., Leth-Møller, K., .
. . Gluud, C. (2017). Selective serotonin reuptake inhibitors versus placebo in patients with
major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analy-
sis. BMC Psychiatry, 17(1), 58. http:// dx. doi. org/ 10. 1186/ s12888- 016- 1173-2
Jorm, A. F., Patten, S. B., Brugha, T. S., & Mojtabai, R. (2017). Has increased provision of treat-
ment reduced the prevalence of common mental disorders? Review of the evidence from four
countries. World Psychiatry, 16(1), 90–99. http:// dx. doi. org/ 10. 1002/ wps. 20388
Kampermann, L., Nestoriuc, Y., & Shedden-Mora, M. C. (2017). Physicians' beliefs about placebo
and nocebo effects in antidepressants - an online survey among German practitioners. Plos One,
12(5), e0178719. http:// dx. doi. org/ 10. 1371/ journal. pone. 0178719
Kantor, E. D., Rehm, C. D., Haas, J. S., Chan, A. T., & Giovannucci, E. L. (2015). Trends in
prescription drug use among adults in the United States from 1999-2012. JAMA, 314(17),
1818–1831. http:// dx. doi. org/ 10. 1001/ jama. 2015. 13766
Kessing, L. V., Hansen, H. V., Demyttenaere, K., & Bech, P. (2005). Depressive and bipolar disor-
ders: Patients' attitudes and beliefs towards depression and antidepressants. Psychological Medi-
cine, 35(8), 1205–1213. http:// dx. doi. org/ 10. 1017/ S0033291705004605
Kirsch, I., Moore, T. J., Scoboria, A., & Nicholls, S. S. (2002). The emperor's new drugs: An analy-
sis of antidepressant medication data submitted to the U. S. Food and Drug Administration.
Prevention & Treatment, 5(1), 23.
Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertise-
ments and the scientific literature. PLoS Medicine, 2(12), e392. http:// dx. doi. org/ 10. 1371/ jour-
nal. pmed. 0020392
Lader, M. (1991). History of benzodiazepine dependence. Journal of Substance Abuse Treatment, 8(1-
2), 53–59. http:// dx. doi. org/ 10. 1016/ 0740- 5472(91)90027-8
Lexchin, J., Bero, L. A., Djulbegovic, B., & Clark, O. (2003). Pharmaceutical industry sponsorship
and research outcome and quality: Systematic review. BMJ, 326(7400), 1167–1170. http:// dx.
doi. org/ 10. 1136/ bmj. 326. 7400. 1167
Lexchin, J., & Light, D. W. (2006). Commercial influence and the content of medical journals.
BMJ, 332(7555), 1444–1447. http:// dx. doi. org/ 10. 1136/ bmj. 332. 7555. 1444
Light, D. W., Lexchin, J., & Darrow, J. J. (2013). Institutional corruption of pharmaceuticals and
the myth of safe and effective drugs. The Journal of Law, Medicine & Ethics, 41(3), 590–600.
http:// dx. doi. org/ 10. 1111/ jlme. 12068
Lundh, A., Sismondo, S., Lexchin, J., Busuioc, O. A., & Bero, L. (2012). Industry sponsorship and
research outcome. The Cochrane Database of Systematic Reviews, 12, MR000033. http:// dx. doi.
org/ 10. 1002/ 14651858. MR000033. pub2
Maund, E., Tendal, B., Hróbjartsson, A., Jørgensen, K. J., Lundh, A., Schroll, J., & Gøtzsche, P. C.
(2014). Benefits and harms in clinical trials of duloxetine for treatment of major depressive dis-
order: Comparison of clinical study reports, trial registries, and publications. BMJ, 348, g3510.
http:// dx. doi. org/ 10. 1136/ bmj. g3510
McCormack, J., & Korownyk, C. (2018). Effectiveness of antidepressants. BMJ, 360, k1073. http://
dx. doi. org/ 10. 1136/ bmj. k1073
14 Hengartner and Plöderl
Medawar, C., Herxheimer, A., Bell, A., & Jofre, S. (2002). Paroxetine, Panorama and user reporting
of ADRs: Consumer intelligence matters in clinical practice and post-marketing drug surveil-
lance. The International Journal of Risk & Safety in Medicine, 15(3-4), 161–169.
Melander, H., Ahlqvist-Rastad, J., Meijer, G., & Beermann, B. (2003). Evidence b(i)ased medicine-
-selective reporting from studies sponsored by pharmaceutical industry: Review of studies in
new drug applications. BMJ, 326(7400), 1171–1173. http:// dx. doi. org/ 10. 1136/ bmj. 326. 7400.
1171
Michelson, D., Fava, M., Amsterdam, J., Apter, J., Londborg, P., Tamura, R., & Tepner, R. G.
(2000). Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, pla-
cebo-controlled trial. The British Journal of Psychiatry, 176(04), 363–368. http:// dx. doi. org/ 10.
1192/ bjp. 176. 4. 363
Moncrieff, J., & Cohen, D. (2006). Do antidepressants cure or create abnormal brain states? PLoS
Medicine, 3(7), e240. http:// dx. doi. org/ 10. 1371/ journal. pmed. 0030240
Moncrieff, J., & Kirsch, I. (2005). Efficacy of antidepressants in adults. BMJ, 331(7509), 155–157.
http:// dx. doi. org/ 10. 1136/ bmj. 331. 7509. 155
Nielsen, M., Hansen, E. H., & Gøtzsche, P. C. (2012). What is the difference between dependence
and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake
inhibitors. Addiction, 107(5), 900–908. http:// dx. doi. org/ 10. 1111/ j. 1360- 0443. 2011. 03686.x
Nutt, D., King, L. A., Saulsbury, W., & Blakemore, C. (2007). Development of a rational scale to
assess the harm of drugs of potential misuse. The Lancet, 369(9566), 1047–1053. http:// dx. doi.
org/ 10. 1016/ S0140- 6736(07)60464-4
Nutt, D. J., Goodwin, G. M., Bhugra, D., Fazel, S., & Lawrie, S. (2014). Attacks on antidepressants:
signs of deep-seated stigma? The Lancet Psychiatry, 1(2), 102–104. http:// dx. doi. org/ 10. 1016/
S2215- 0366(14)70232-9
OECD. (2012). Sick on the job? Myths and realities about mental health and work. Paris, France: OECD
Publishing.
Perahia, D. G., Kajdasz, D. K., Desaiah, D., & Haddad, P. M. (2005). Symptoms following abrupt
discontinuation of duloxetine treatment in patients with major depressive disorder. Journal of
Affective Disorders, 89(1-3), 207–212. http:// dx. doi. org/ 10. 1016/ j. jad. 2005. 09. 003
Perlis, R. H., Perlis, C. S., Wu, Y., Hwang, C., Joseph, M., & Nierenberg, A. A. (2005). Industry
sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.
American Journal of Psychiatry, 162(10), 1957–1960. http:// dx. doi. org/ 10. 1176/ appi. ajp. 162. 10.
1957
Pigott, H. E. (2011). STAR*D: A tale and trail of bias. Ethical Human Psychology and Psychiatry,
13(1), 6–28. http:// dx. doi. org/ 10. 1891/ 1559- 4343. 13. 1.6
Pigott, H. E., Leventhal, A. M., Alter, G. S., & Boren, J. J. (2010). Efficacy and effectiveness of
antidepressants: Current status of research. Psychotherapy and Psychosomatics, 79(5), 267–279.
http:// dx. doi. org/ 10. 1159/ 000318293
Rabinowitz, J., Werbeloff, N., Mandel, F. S., Menard, F., Marangell, L., & Kapur, S. (2016). Initial
depression severity and response to antidepressants v. placebo: Patient-level data analysis from
34 randomised controlled trials. British Journal of Psychiatry, 209(5), 427–428. http:// dx. doi. org/
10. 1192/ bjp. bp. 115. 173906
Read, J., & Cain, A. (2013). A literature review and meta-analysis of drug company-funded men-
tal health websites. Acta Psychiatrica Scandinavica, 128(6), 422–433. http:// dx. doi. org/ 10. 1111/
acps. 12146
Read, J., Cartwright, C., & Gibson, K. (2014). Adverse emotional and interpersonal effects reported
by 1829 New Zealanders while taking antidepressants. Psychiatry Research, 216(1), 67–73.
http:// dx. doi. org/ 10. 1016/ j. psychres. 2014. 01. 042
Rosenbaum, J. F., Fava, M., Hoog, S. L., Ascroft, R. C., & Krebs, W. B. (1998). Selective serotonin
reuptake inhibitor discontinuation syndrome: A randomized clinical trial. Biological Psychiatry,
44(2), 77–87. http:// dx. doi. org/ 10. 1016/ S0006- 3223(98)00126-7
15False Beliefs in Academic Psychiatry
Schomerus, G., Schwahn, C., Holzinger, A., Corrigan, P. W., Grabe, H. J., Carta, M. G., & Anger-
meyer, M. C. (2012). Evolution of public attitudes about mental illness: A systematic review
and meta-analysis. Acta Psychiatrica Scandinavica, 125(6), 440–452. http:// dx. doi. org/ 10. 1111/
j. 1600- 0447. 2012. 01826.x
Sir, A., D'Souza, R. F., Uguz, S., George, T., Vahip, S., Hopwood, M., & Burt, T. (2005). Random-
ized trial of sertraline versus venlafaxine XR in major depression: Efficacy and discontinuation
symptoms. The Journal of Clinical Psychiatry, 66(10), 1312–1320.
Smith, R. (2005). Medical journals are an extension of the marketing arm of pharmaceutical compa-
nies. PLoS Medicine, 2(5), e138. http:// dx. doi. org/ 10. 1371/ journal. pmed. 0020138
Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008). Selective pub-
lication of antidepressant trials and its influence on apparent efficacy. New England Journal of
Medicine, 358(3), 252–260. http:// dx. doi. org/ 10. 1056/ NEJMsa065779
Vijapura, S., Laferton, J. A., Mintz, D., Kaptchuk, T. J., & Wolfe, D. (2016). Psychiatrists' attitudes
toward non-pharmacologic factors within the context of antidepressant pharmacotherapy.
Academic Psychiatry, 40(5), 783–789. http:// dx. doi. org/ 10. 1007/ s40596- 015- 0470-2
Vilhelmsson, A. (2013). Depression and antidepressants: A nordic perspective. Frontiers in Public
Health, 1, 30. http:// dx. doi. org/ 10. 3389/ fpubh. 2013. 00030
Whitaker, R. (2005). Anatomy of an epidemic: Psychiatric drugs and the astonishing rise of mental
illness in America. Ethical Human Psychology and Psychiatry, 7(1), 23–35.
Whitaker, R., & Cosgrove, L. (2015). Psychiatry under the influence. London, UK: Palgrave Macmil-
lan.
Michael P. Hengartner, PhD, is a senior researcher and lecturer affiliated with the Zurich Univer-
sity of Applied Psychology. He teaches psychopathology, psychotherapy research, and biostatistics.
His main research interests are psychiatric epidemiology, public mental health, social psychiatry,
and psychosomatics.
Martin Plöderl, PhD, is a clinical psychologist and psychotherapist and currently affiliated with the
Department for Crisis Intervention and Suicide Prevention at the Christian Doppler Clinic, Para-
celsus Medical University, Salzburg, Austria. His main research focus is about suicide prevention
and suicide risk of sexual minority individuals.
Acknowledgments. The authors thank the many antidepressant users who shared their personal
experiences with them. This work conforms to the journal’s editorial policy and ethical standards
in medical research.
Correspondence regarding this article should be directed to Michael P. Hengartner, PhD, Depart-
ment of Applied Psychology, Zurich University of Applied Sciences (ZHAW), CH-8037 Zurich,
Switzerland. E-mail: michaelpascal. hengartner@ zhaw. ch
16 Hengartner and Plöderl
... 13,19 Despite this evidence, many doctors and psychiatrists are reluctant to accept patients are presenting with withdrawal from the medications. 19,[24][25][26] Recent data on antidepressant prescribing rates show large year on year increases. 27,28 In England, prescription rates doubled in the decade to 2018 and, in that year, 70.9 million antidepressant prescriptions were issue in the United Kingdom (UK). ...
... In the meantime, online communities still appear to be a very important avenue of choice for patients seeking support when tapering off these drugs. 24 Once they realise their doctor cannot help them safely withdraw, or mis-diagnose their withdrawal symptoms as relapse or emergence of a new illness, 26 there are few alternate options for support. ...
... More importantly, clinicians do not recognise the symptoms of antidepressant withdrawal, often misdiagnosing it as relapse of previous symptoms. 21,24,26 There is also evidence of huge denial journals.sagepub.com/home/tpp 15 of withdrawal severity and duration from clinicians. ...
Article
Full-text available
Background Antidepressant withdrawal is experienced by about half of people who try to reduce or come off their medication. It can be a debilitating, long lasting process. Many clinicians misdiagnose or minimise symptoms, inadvertently prolonging suffering. Most are unable to help patients safely taper off. There has been little research into the peer support communities that are playing an increasingly important role in helping people withdraw from psychiatric medications. Methods To illustrate the growth and activities of Facebook withdrawal groups, we examined 13 such groups. All were raising awareness of, and supporting individuals tapering off, antidepressants and were followed for 13 months. A further three groups were added for the last 5 months of the study. Results In June 2020, the groups had a total membership of 67,125, of which, 60,261 were in private groups. The increase in membership for the 13 groups over the study period was 28.4%. One group was examined in greater detail. Group membership was 82.5% female, as were 80% of the Administrators and Moderators, all of whom are lay volunteers. Membership was international but dominated (51.2%) by the United States (US). The most common reason for seeking out this group was failed clinician-led tapers. Discussion The results are discussed in the context of research on the prevalence, duration and severity of antidepressant withdrawal. We question why so many patients seek help in peer-led Facebook groups, rather than relying on the clinicians that prescribed the medications. The withdrawal experiences of tens of thousands of people remain hidden in these groups where they receive support to taper when healthcare services should be responsible. Further research should focus on the methods of support and tapering protocols used in these groups to enable improved, more informed support by clinicians. Support from Governments and healthcare agencies is also needed, internationally, to address this issue.
... As well as the heated debate about the merits of antidepressants, it is argued that another important discrepancy between the scientific literature and prevailing beliefs held by leading psychiatrists concerns withdrawal symptoms on discontinuation of antidepressant medication. 12 According to several studies, severe and persistent withdrawal reactions affect up to 50% of antidepressant users. Others quote that more than 50% of people who attempted to stop antidepressants experienced withdrawal effects and nearly 50% of those experiencing withdrawal effects described them as severe. 1 Notably, in our study the psychiatrists considered withdrawal effects to be more severe than the GPs. ...
... Antidepressant withdrawal is a serious public health concern that warrants more research and adequate appraisal by academic psychiatry. 12 It is interesting to note such a high variation in responses from all participants. The diversity of responses reflects the wide variation in results from research studies. ...
Article
Full-text available
Background There has been a recent rise in antidepressant prescriptions. After the episode for which it was prescribed, the patient should ideally be supported in withdrawing the medication. There is increasing evidence for withdrawal symptoms (sometimes called discontinuation symptoms) occurring on ceasing treatment, sometimes having severe or prolonged effects. Aims To identify and compare current knowledge, attitudes and practices of general practitioners (GPs) and psychiatrists in Cornwall, UK, concerning antidepressant withdrawal symptoms. Method Questions about withdrawal symptoms and management were asked of GPs and psychiatrists in a multiple-choice cross-sectional study co-designed with a lived experience expert. Results Psychiatrists thought that withdrawal symptoms were more severe than GPs did ( P = 0.003); 53% (22/42) of GPs and 69% (18/26) of psychiatrists thought that withdrawal symptoms typically last between 1 and 4 weeks, although there was a wide range of answers given; 35% (9/26) of psychiatrists but no GPs identified a pharmacist as someone they may use to help manage antidepressant withdrawal. About three-quarters of respondents claimed they usually or always informed patients of potential withdrawal symptoms when they started a patient on antidepressants, but patient surveys say only 1% are warned. Conclusions Psychiatrists and GPs need to effectively warn patients of potential withdrawal effects. Community pharmacists might be useful in supporting GP-managed antidepressant withdrawal. The wide variation in responses to most questions posed to participants reflects the variation in results of research on the topic. This highlights a need for more reproducible studies to be carried out on antidepressant withdrawal, which could inform future guidelines.
... Although this observer rating is intended to capture patient change reliably, preliminary evidence indicates that clinicians often fail to recognize or report negative outcomes (Dimidjian and Hollon, 2010;Hatfield et al., 2009). Similarly, clinicians' prognoses of treatment outcomes for ongoing cases are frequently inaccurate (Hannan et al., 2005), the effects of their treatments are often overestimated and side effects are neglected (Hengartner and Plöderl, 2018). Finally, clinicians tend to overestimate their competence (Walfish et al., 2012), possibly providing an additional source of bias in outcome assessment. ...
Article
Full-text available
Background: Divergent outcomes of treatment for depression occur regularly, but often go undetected by clinical judgment alone. To date, no comprehensive studies are available on what the detection rate of divergent outcomes is in routine care. Method: We analyzed a large (N = 20,882) database of clinician-rated and patient-reported outcomes from routine inpatient treatment for depression. Results: There was little agreement (57.7% on the GAF, 7.8% on the CGI-I) between clinician ratings and patients not showing clinically significant change. There was virtually no agreement (0.6% on the GAF, 2% on the CGI-I) between clinician ratings and self-report scales in deteriorated patients. Multiple regression showed that clinician ratings of change were influenced primarily by symptom severity at discharge, rather than change from admission. Limitations: Only symptom scales were available as patient-reported outcomes, although clinician ratings may be based on other sources of information. In addition, no information was available on clinicians' experience with the rating scales used, nor is it clear how carefully the ratings were made. Discussion: It can be concluded that failure to achieve treatment success and worsening after routine treatment for depression often go undetected on clinical rating scales, suggesting that such cases frequently remain undetected. Clinicians should generally obtain patient-reported outcomes during treatment to detect these cases.
... 38,[62][63][64][65][66][67] Unfortunately, until very recently, medical associations, pharmaceutical companies, drug regulators, psychiatric academics, and practitioners have largely neglected or minimized this serious public health issue. 15,16,68,69 Therefore, we hope that our study of PWS from antidepressants, which is the largest conducted to date, may prompt more research on this largely unexplored syndrome. We further hope that our findings may help general practitioners (GPs) and mental health professionals to better recognize and take steps to avoid this severe and debilitating condition, 15,29,30,70 which can lead even to suicide. ...
Article
Full-text available
Background: Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods: We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org, a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results: In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion: PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms. Keywords antidepressant, discontinuation, PAWS, persistent post-withdrawal disorder, protracted
... Clovis et al., 2012). They also may adhere to false beliefs prevalent in their specialty, such as psychiatrists who discount the evidence that antidepressants create physical dependence and significant, common withdrawal symptoms (Hengartner & Plöderl, 2018). In addition, some providers may rely on unsound clinical evidence (Ioannidis et al., 2017) or literature tainted by citation bias, as when studies about the high prevalence of smoking among schizophrenics are over-cited despite an average smoking prevalence in that population (Chapman et al., 2009). ...
Chapter
Full-text available
Research on health misinformation has grown rapidly as concerns about the potential harmful effects of health misinformation on individuals and society intensify amid a “post-truth” era. In this chapter, we provide a broad overview of current research and evidence concerning the many facets of health misinformation, including its sources, prevalence, characteristics (both content and diffusion features), impact, and mitigation. We conclude that health misinformation originates from many sources, most notably mass and social media; is fairly prevalent, both in interpersonal and mediated settings; and tends to feature negative sentiments, anecdotal evidence, and anti-science narratives. Although there is no conclusive evidence that health misinformation spreads more broadly than scientific information, health misinformation reliably leads to misperceptions on health issues. Efforts to mitigate the impact of health misinformation show early promise in correcting misperceptions. We offer several directions for future research.
... Providers including doctors, nurses, dental hygienists, medical students, and pharmacists spread misinformation to patients through inadequate knowledge (e.g. Clovis et al., 2012), adhering to false beliefs prevalent in their specialty (Hengartner & Plöderl, 2018), and by relying on unsound clinical evidence (Ioannidis et al., 2017) or literature tainted by citation bias (Chapman et al., 2009). As with non-professionals, practitioners also disseminate and consume misinformation via social media (Chua & Banerjee, 2018). ...
Chapter
Full-text available
Research on health misinformation has grown rapidly as concerns about the potential harmful effects of health misinformation on individuals and society intensify amid a “post-truth” era. In this chapter, we provide a broad overview of current research and evidence concerning the many facets of health misinformation, including its sources, prevalence, characteristics (both content and diffusion features), impact, and mitigation. We conclude that health misinformation originates from many sources, most notably mass and social media, is fairly prevalent, both in interpersonal and mediated settings, and tends to feature negative sentiments, anecdotal evidence, and anti-science narratives. While there is no conclusive evidence that health misinformation spreads more broadly than scientific information, health misinformation reliably leads to misperceptions on health issues. Efforts to mitigate the impact of health misinformation show early promise in correcting misperceptions. We offer several directions for future research, including a call for more investigations on the impact of health misinformation and correcting messages on actual behaviors.
... 38,[62][63][64][65][66][67] Unfortunately, until very recently, medical associations, pharmaceutical companies, drug regulators, psychiatric academics, and practitioners have largely neglected or minimized this serious public health issue. 15,16,68,69 Therefore, we hope that our study of PWS from antidepressants, which is the largest conducted to date, may prompt more research on this largely unexplored syndrome. We further hope that our findings may help general practitioners (GPs) and mental health professionals to better recognize and take steps to avoid this severe and debilitating condition, 15,29,30,70 which can lead even to suicide. ...
Article
Full-text available
Background Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org , a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.
Article
Approximately half of the tens of millions of people currently taking antidepressants will experience withdrawal symptoms when they try to reduce or come off them. Nearly half of these describe their symptoms as severe in surveys. Many prescribing doctors seem ill-informed and unprepared to provide effective discontinuation advice and support, often misdiagnosing withdrawal as a relapse of depression or anxiety. 708 members of online support groups for people on antidepressants, from 31 countries, completed a sentence in an online survey: 'A public health service to help people come off antidepressants should include ................'. Two independent researchers categorised their responses into themes, and then reached consensus via discussion. Seven themes emerged: 'Prescriber Role', 'Information', 'Other Supports/Services', 'Strong Negative Feelings re Doctors/Services etc.', Informed Consent When Prescribed', 'Drug Companies' and: 'Public Health Campaign'. The most frequently mentioned requirements of the Prescriber Role were that prescribers be properly informed, provide small doses/liquid/tapering strips, develop a withdrawal plan and believe patients about their withdrawal experiences. The most frequently recommended other services were psychotherapy/counselling, support groups, patient led/informed services, nutrition advice, 24-hour crisis support and 'holistic/lifestyle' approaches. Many respondents were angry about how uninformed their doctors were and how they had been treated.
Chapter
In many cases, the prescription medications are not taken as prescribed is because of failure to adhere to the medication regimen. The reason for not adhering to drug treatment include unpleasant or inconvenient side effects of the medications; dry mouth, change in taste, fatigue or frequent urination are various reasons of stopping a mediation. Older adults are at higher risk for medication nonadherence due to prevalence of multiple comorbidities, including cognitive deficit and polypharmacy. Medication adherence can be enhanced by considering geriatric's vision, hearing, swallowing, cognition, motor impairment, and health literacy while providing counselling and education. On the positive side, a study found that increased medication adherence was associated with fewer hospitalizations and decreased cost in patients with certain chronic medical conditions (e.g., diabetes, hypertension).
Article
Background: Public Health England has recommended that services be put in place to support people who choose to withdraw from antidepressants because of a current gap. This study aims to explore the views of members of online withdrawal peer-support groups about existing healthcare and what additional support is needed. Methods: The administrators of 15 online support groups for people stopping antidepressants were asked to advertise an online survey to their members. The survey, which was online from May 2021 to April 2022, was completed by 1276 people from 49 countries. Results: 71% of respondents found their doctors' advice unhelpful (57% 'very unhelpful') regarding stopping an antidepressant; the main reasons being 'Recommended a reduction rate that was too quick for me', 'Not familiar enough with withdrawal symptoms to advise me' and 'Suggested stopping antidepressants would not cause withdrawal symptoms'. One in three did not seek advice from their prescriber when deciding whether to withdraw, with the main reasons being 'I felt they would not be supportive' (58%) and 'I felt that they didn't have the expertise to help me' (51%). The most common prescriber responses to those who did seek advice was 'Suggested a quick withdrawal schedule' (56%) and 'Not supportive and offered no guidance' (27%). The most common discontinuation periods recommended by doctors were one month (23%) and two weeks (19%). A range of potential professional services were rated 'very useful', most frequently: 'Access to smaller doses (e.g. tapering strips, liquid, smaller dose tablets) to ensure gradual reduction' (88%) and 'A health professional providing a personalised, flexible reduction plan' (79%). Limitations: This was a convenience sample, which may have been biased towards people who took longer to withdraw, and experienced more withdrawal symptoms, than antidepressant users in general. Black and ethnic minority people, and people without access to the internet, were underrepresented. Conclusions: Most participants reported their prescribers were unable to help them safely stop antidepressants, compelling them to turn to online peer-support groups instead. Our findings indicate, in keeping with previous studies, that clinicians require upskilling in safe tapering of antidepressants, and that patients need specialised services to help them stop safely.
Article
Full-text available
Antidepressants are commonly prescribed for many mental disorders, including psychosis. Withdrawal effects, resulting from inappropriately short duration of tapering or lack of flexibility in prescribing gradual reduction, are common. An observational study was conducted of the use of “tapering strips”, which allow gradual dosage reduction and minimise the potential for withdrawal effects. A tapering strip consists of antidepressant medication, packaged in a roll of small daily pouches, each with the same or slightly lower dose than the one before it. Strips come in series covering 28 days. Of 1194 users of tapering strips, 895 (75%) wished to discontinue their antidepressant medication. In these 895, median length of antidepressant use was 2–5 years (IQR: 1–2 years– > 10 years). Nearly two-thirds (62%) had unsuccessfully attempted withdrawal before (median = 2 times before, IQR 1–3). Almost all of these (97%) had experienced some degree of withdrawal, with 49% experiencing severe withdrawal (7 on a scale of 1–7, IQR 6–7). The most common medications were paroxetine (n = 423, 47%) and venlafaxine (n = 386, 43%). Of the 895 wishing to discontinue, 636 (71%) succeeded in tapering their antidepressant medication completely, using a median of 2 tapering strips (IQR 1–3) over a median of 56 days (IQR = 28–84). Tapering strips represent a simple and effective method of achieving a gradual dosage reduction.
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Background: In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants’ efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Methods: Narrative review based on a comprehensive search of the literature. Results: It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies spontaneous remitters are excluded whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at increased risk of suicide and that they have a higher rate of all-cause mortality than matched controls. Conclusions: The strong reliance on industry-funded research results in an uncritical approval of antidepressants. Due to several flaws such as publication and reporting bias, unblinding of outcome assessors, concealment and re-coding of serious adverse events, the efficacy of antidepressants is systematically overestimated and harm is systematically underestimated. I therefore conclude that antidepressants are largely ineffective and potentially harmful.
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Background While substantial placebo and nocebo effects have been documented in antidepressant clinical trials, physicians' awareness of the nonspecific effects in routine antidepressant treatment remains unclear. The study investigated physicians' beliefs and explanatory models regarding the desired effects and undesired side effects of antidepressants, with specific emphasis on nonspecific effects accounted for by placebo and nocebo mechanisms. Methods An online survey was conducted among 87 physicians (40.2% psychiatrists, 25.3% neurologists, 24.1% general practitioners, 12.6% internists, 21.8% other). The survey assessed the physician's beliefs in antidepressant effectiveness, as well as 6 explanatory models regarding antidepressant effectiveness and 8 explanatory models for the occurrence of side effects. Results Most physicians (89.7%) believed in the effectiveness of antidepressants while acknowledging a considerable role of the placebo effect by attributing around 40% of the total effects to nonspecific factors. For both antidepressant effectiveness and the occurrence of side effects, pharmacological effects were rated as most important (93.1% and 80.5% agreement), but physicians also attributed a substantial role to the patients' expectations (63.2% and 58.6%) and experiences (60.9% and 56.3%). Concerning the physician's own role in promoting nonspecific effects in antidepressant effectiveness, highest endorsements were found for the Quality of the physician-patient-relationship (58.6%) and own expectations (41.4%). When asked about side effects, fewer participants agreed that informing the patient about known side effects (25.2%) or the physicians' expectations themselves (17.2%) could induce side effects. Conclusion Physicians, when prescribing antidepressants, are generally open towards nonspecific treatment mechanisms. However, they consider their own influence as less important than the patient's side, especially when it comes to the explanation of unwanted side effects. Awareness of the possible beneficial as well as malicious role of nonspecific mechanisms should be fostered as the first step towards optimizing antidepressant treatment by promoting placebo while avoiding nocebo effects.
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Background The evidence on selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder is unclear. Methods Our objective was to conduct a systematic review assessing the effects of SSRIs versus placebo, ‘active’ placebo, or no intervention in adult participants with major depressive disorder. We searched for eligible randomised clinical trials in The Cochrane Library’s CENTRAL, PubMed, EMBASE, PsycLIT, PsycINFO, Science Citation Index Expanded, clinical trial registers of Europe and USA, websites of pharmaceutical companies, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency until January 2016. All data were extracted by at least two independent investigators. We used Cochrane systematic review methodology, Trial Sequential Analysis, and calculation of Bayes factor. An eight-step procedure was followed to assess if thresholds for statistical and clinical significance were crossed. Primary outcomes were reduction of depressive symptoms, remission, and adverse events. Secondary outcomes were suicides, suicide attempts, suicide ideation, and quality of life. ResultsA total of 131 randomised placebo-controlled trials enrolling a total of 27,422 participants were included. None of the trials used ‘active’ placebo or no intervention as control intervention. All trials had high risk of bias. SSRIs significantly reduced the Hamilton Depression Rating Scale (HDRS) at end of treatment (mean difference −1.94 HDRS points; 95% CI −2.50 to −1.37; P < 0.00001; 49 trials; Trial Sequential Analysis-adjusted CI −2.70 to −1.18); Bayes factor below predefined threshold (2.01*10−23). The effect estimate, however, was below our predefined threshold for clinical significance of 3 HDRS points. SSRIs significantly decreased the risk of no remission (RR 0.88; 95% CI 0.84 to 0.91; P < 0.00001; 34 trials; Trial Sequential Analysis adjusted CI 0.83 to 0.92); Bayes factor (1426.81) did not confirm the effect). SSRIs significantly increased the risks of serious adverse events (OR 1.37; 95% CI 1.08 to 1.75; P = 0.009; 44 trials; Trial Sequential Analysis-adjusted CI 1.03 to 1.89). This corresponds to 31/1000 SSRI participants will experience a serious adverse event compared with 22/1000 control participants. SSRIs also significantly increased the number of non-serious adverse events. There were almost no data on suicidal behaviour, quality of life, and long-term effects. ConclusionsSSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable. SSRIs significantly increase the risk of both serious and non-serious adverse events. The potential small beneficial effects seem to be outweighed by harmful effects. Systematic review registrationPROSPERO CRD42013004420.
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Previous research has shown that reporting bias has inflated the apparent efficacy of antidepressants. We investigated whether apparent safety was also affected. We included 133 trials, involving 31,296 patients, of second-generation antidepressants for the treatment of major depressive disorder (MDD) or anxiety disorders, obtained from Food and Drug Administration (FDA) reviews. We extracted data on overall discontinuation, discontinuation due to adverse events, and serious adverse events (SAEs). Meta-analysis was used to compare discontinuation rates between FDA reviews and matching journal articles, while SAEs were compared qualitatively. The odds ratio for overall discontinuation, comparing drug to placebo, was 1.0 for both sources, while that for discontinuation due to adverse events was 2.4 for both sources. Seventy-seven of 97 (79%) journal articles provided incomplete information on SAEs; sixty-one (63%) articles made no mention of SAEs at all. Of 21 articles which could be compared to the FDA, only 6 (29%) had full reporting without discrepancies. Nine (43%) articles reported a discrepant number of SAEs. Descriptions were absent or discrepant in 6 (29%) additional articles, even for important SAEs such as suicide attempts. In conclusion, reporting bias has not affected average discontinuation rates over trials. However, SAE reporting is not only very poor, with over half of articles failing to discuss SAEs altogether, but discrepancies between the FDA and articles were common and often led to a more favorable drug-placebo comparison. These findings suggest that journal articles are an unreliable source of data on SAEs in antidepressant trials.
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Psychiatry Under the Influence investigates how the influence of pharmaceutical money and guild interests has corrupted the behavior of the American Psychiatric Association and academic psychiatry during the past 35 years. The book documents how the psychiatric establishment regularly misled the American public about what was known about the biology of mental disorders, the validity of psychiatric diagnoses, and the safety and efficacy of its drugs. It also looks at how these two corrupting influences encouraged the expansion of diagnostic boundaries and the creation of biased clinical practice guidelines. This corruption has led to significant social injury, and in particular, a societal lack of informed consent regarding the use of psychiatric drugs, and the pathologizing of normal behaviors in children and adults. The authorsargues that reforming psychiatry will require the neutralization of these two corrupting influences—pharmaceutical money and guild interests—and the establishment of multidisciplinary authority over the field of mental health.
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Several often-cited meta-analysis have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug-placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry. Although our trial-level data support prevous findings, patient-level data do not; initial severity and outcomes were similarly related in treatment and placebo groups.