Antidepressant withdrawal – the tide is finally turning

Abstract

Withdrawal reactions when coming off antidepressants have long been neglected or minimised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs) entered the market for the first systematic review to be published. More reviews have followed, demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the sparse but growing evidence base. What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe. These findings are now increasingly acknowledged by official professional bodies and societies.

Full text

Epidemiology and Psychiatric
Sciences
cambridge.org/eps
Editorial
Cite this article: Hengartner MP, Davies J,
Read J (2019). Antidepressant withdrawal –
the tide is finally turning. Epidemiology and
Psychiatric Sciences 1–3. https://doi.org/
10.1017/S2045796019000465
Received: 18 July 2019
Accepted: 27 July 2019
Key words:
Administration; adverse effects;
antidepressants; depression; drug side effects
other
Author for correspondence:
Michael P. Hengartner, E-mail: heng@zhaw.ch
© The Author(s) 2019. This is an Open Access
article, distributed under the terms of the
Creative Commons Attribution licence (http://
creativecommons.org/licenses/by/4.0/), which
permits unrestricted re-use, distribution, and
reproduction in any medium, provided the
original work is properly cited.
Antidepressant withdrawal –the tide is
finally turning
Michael P. Hengartner1, James Davies2,3 and John Read4,5
1
Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland;
2
Department of Life Sciences, University of Roehampton, London, UK;
3
All-Party Parliamentary Group for
Prescribed Drug Dependence, London, UK;
4
School of Psychology, University of East London, London, UK and
5
International Institute for Psychiatric Drug Withdrawal, Gothenburg, Sweden
Abstract
Withdrawal reactions when coming off antidepressants have long been neglected or mini-
mised. It took almost two decades after the selective serotonin reuptake inhibitors (SSRIs)
entered the market for the first systematic review to be published. More reviews have followed,
demonstrating that the dominant and long-held view that withdrawal is mostly mild, affects
only a small minority and resolves spontaneously within 1–2 weeks, was at odd with the
sparse but growing evidence base. What the scientific literature reveals is in close agreement
with the thousands of service user testimonies available online in large forums. It suggests that
withdrawal reactions are quite common, that they may last from a few weeks to several months
or even longer, and that they are often severe. These findings are now increasingly acknowl-
edged by official professional bodies and societies.
Like most other central nervous system drugs, including benzodiazepines, alcohol or heroin,
selective serotonin reuptake inhibitor (SSRI) antidepressants may cause withdrawal reactions
upon discontinuing the drug, especially after prolonged use (Nielsen et al., 2012; Chouinard
and Chouinard, 2015). This was first officially acknowledged, but minimised as a minor ‘dis-
continuation syndrome’, by an industry sponsored consensus panel in the late 1990s, that is,
about 10 years after the first SSRI –fluoxetine –was approved as a depression treatment
(Schatzberg et al., 1997). Since then, withdrawal reactions were sporadically studied and dis-
cussed in the scientific literature (e.g. Rosenbaum et al., 1998; Haddad, 2001; Baldwin et al.,
2007). Common withdrawal symptoms include anxiety, irritability, agitation, dysphoria,
insomnia, fatigue, tremor, sweating, shock-like sensations (‘brain zaps’), paraesthesia, vertigo,
dizziness, nausea, vomiting, confusion and decreased concentration (Fava et al., 2015).
Although controlled clinical trials and observational studies have revealed remarkably high
rates of withdrawal reactions emerging shortly after discontinuation (Rosenbaum et al.,
1998; Sir et al., 2005;Favaet al., 2007), the preferred narrative in academic psychiatry has
always been that withdrawal problems affect only a small minority, are mostly mild and resolve
spontaneously within 1–2 weeks (e.g. Burn and Baldwin, 2018). This has also been the official
position of both the American Psychiatric Association (APA) and National Institute for Health
and Care Excellence (NICE) and many leading psychiatrists in the USA and the UK since the
early 2000s (National Institute for Health and Care, 2009; American Psychiatric Association,
2010), although, as we will soon state, this position has now changed owing to its being con-
trary to the evidence base (Davies and Read, 2019a; Davies et al., 2019; Horowitz and Taylor,
2019). Below we will therefore outline what conclusions and practical implications can be
drawn from the sparse, but vitally important, scientific evidence available.
The first systematic review of SSRI withdrawal reactions was published in 2015 by Fava
et al.(2015). A few years after their SSRI review, Fava and colleagues also published a system-
atic review on serotonin-norepinephrine reuptake inhibitor withdrawal (Fava et al., 2018). Two
further reviews have recently been published (Jha et al., 2018; Davies and Read, 2019a). The
four reviews converged on the main finding that the occurrence of withdrawal reactions is
quite common, affecting between 30 and 60% of antidepressant users when they try to
come off, depending on the methodology deployed (short-term randomised-controlled trials
based on pre-selected participants produced somewhat lower estimates than more representa-
tive naturalistic studies and large surveys including many long-term users) and on the drugs
considered (drugs with a short elimination half-life appear to cause more withdrawal reactions
than drugs with a long elimination half-life).
However, there were also points of disagreement between the reviews. For instance, Jha
et al.(
2018) claimed that in the vast majority of users, withdrawal symptoms resolve in 2–3
weeks. Their review was not systematic, but selective in the literature it chose to cite –e.g.
it was pointed out that their 2–3 weeks statement was not only arbitrary but at odds with
the very evidence they cited (Fava and Cosci, 2019; Hengartner et al., 2019). The reviews by
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Fava et al.(2015) and Davies and Read (2019a) were more in
accord with each other, showing that the duration of withdrawal
symptoms is highly variable, ranging from a few weeks to several
months, and occasionally longer. For instance, various studies,
using a range of methods, revealed withdrawal durations for
over 2 weeks in 55% of patients (Perahia et al., 2005), at least
12 weeks in 25% (RCPsych, 2012), and, in another, for a mean
duration of 43 days (Narayan and Haddad, 2011). Durations of
more than a year are reported in two recent community samples
of people experiencing withdrawal reactions –by 38.6% (Davies
et al., 2018) and for a mean duration of 90.5 weeks (Stockmann
et al., 2018). In short, the claim that withdrawal resolves spontan-
eously in 1–2or2–3 weeks as stated in the NICE and APA treat-
ment guidelines, and by Jha et al.(2018), conflicts with the
current evidence base.
Another point of disagreement concerned the incidence of
withdrawal reactions when drugs were tapered. While Jha et al.
(2018) claimed that withdrawal occurs mainly when drugs are dis-
continued abruptly, Fava and colleagues maintained that even the
common gradual tapers over a few weeks could not substantially
reduce the risk of withdrawal reactions (Fava et al., 2015; Fava and
Cosci, 2019), a view also supported by recent work published in
Lancet Psychiatry, where withdrawal can span over extensive
tapering periods (Horowitz and Taylor, 2019). Finally, unlike
the other reviews, Davies and Read (2019a) also assessed the
severity of withdrawal reactions and found that just under half
of all people concerned (46%) rated their withdrawal as severe.
Several reactions to these reviews are noteworthy. However,
before we turn to some controversies surrounding antidepressant
withdrawal, we first want to point out that there has been a dearth
of empirical research on this important issue over the years. As
stated above, the first systematic review on withdrawal was not
published until 2015. This is remarkable, given that prescribing
rates have consistently risen, to alarming levels, over the last
20 years (Davies and Read, 2019a), and that almost 200
meta-analyses on the efficacy of new-generation antidepressant
have been published between 2007 and 2014 alone, many with
industry involvement (Ebrahim et al., 2016). Therefore, although
it has recently been claimed, by some British psychiatrists, that the
psychiatric profession has long recognised the issue of withdrawal
(Jauhar et al., 2019), systematic research into possible harms
related to antidepressant discontinuation has obviously been a
low priority, for both academic psychiatrists and for the industry.
The public and professional perception of antidepressant with-
drawal changed dramatically when Davies and Read (2019a) pub-
lished their systematic review. In addition to huge media coverage,
in particular in the UK, there were also some astonishingly fierce
attacks on both the review and on the authors personally by
prominent UK psychiatrists (Jauhar and Hayes, 2019; Jauhar
et al., 2019). The attacks contended that the incidence and sever-
ity of withdrawal reactions has been exaggerated. They also
accused Davies and Read of being biased and partisan. The
major critiques of the original review were exposed as misleading
or inaccurate (Davies and Read, 2019b; Hengartner, 2019). As for
their insinuations about ‘intellectual bias’, we contend that having
a clear evidence-based opinion is of lesser concern than the exten-
sive financial conflicts of interests involving drug companies
declared in Jauhar et al.(2019).
The duration of antidepressant usage has steadily increased
over the years (Huijbregts et al., 2017; Mars et al., 2017), while
large proportions of users indicate that they feel ‘addicted’to
the drugs and experience withdrawal effects (Kessing et al.,
2005; Read and Williams, 2018; Read et al., 2018). Moreover, sev-
eral clinical trials aimed at discontinuing long-term antidepres-
sant prescriptions failed to successfully withdraw a majority of
patients from the drugs despite slow and gradual tapers
(Eveleigh et al., 2018; Fava and Belaise, 2018). Yet, academic
psychiatry has long clung to the illusion that withdrawal reactions,
or discontinuation symptoms, are minor problems that affect only
a small minority and which resolve spontaneously within 1–2
weeks, despite a clear lack of supporting evidence (Hengartner
and Plöderl, 2018; Davies and Read, 2019a).
We have therefore urged the organisations responsible for
depression treatment guidelines to revise their recommendations
and to acknowledge that severe withdrawal reactions are much
more common than previously believed (Davies et al., 2019).
Presumably millions of long-term antidepressant users need
help and the difficulties they experience upon discontinuing the
drugs need to be detected and correctly diagnosed. Currently,
general practitioners who refer to NICE guidelines are likely to
misdiagnose withdrawal effects lasting more than 1–2 weeks as
the depression returning, and, instead of providing support over
a gradual (but individually tailored) withdrawal period, may
inappropriately continue or even increase prescriptions.
Fortunately, the tide is finally turning. Firstly, the psychiatric
profession has started to acknowledge that these serious issues
have long been neglected and minimised. For instance, in May
of this year the Royal College of Psychiatrists in the UK published
an official statement that severe antidepressant withdrawal needs
proper recognition (RCPsych, 2019). Moreover, two psychiatric
researchers who personally experienced severe withdrawal, devel-
oped a neuropharmacological model of gradual taper to mitigate
withdrawal symptoms (Horowitz and Taylor, 2019), and a Dutch
team developed tapering strips that help users to withdraw the
drugs more safely (Groot and van Os, 2018). Secondly, and per-
haps most significantly, in response to the new evidence we
have discussed here, NICE has committed to reviewing its pos-
ition, held for over 14 years, that antidepressant withdrawal is
usually mild resolving over about a week.
We hope that these advances in research and practice will ultim-
ately benefit the millions of antidepressant users who need help. In
September of this year researchers, clinicians and ‘experts-
by-experience’from 12 countries will gather in Gothenburg for a
meeting of the recently formed International Institute for
Psychiatric Drug Withdrawal (http://www.iipdw.com). It does seem
that the academic and clinical communities are finally beginning
to grapple with the issues that the international online community
of antidepressant users (e.g. http://www.letstalkwithdrawal.com;
https://www.survivingantidepressants.org) have long been addres-
sing. It is welcome that academic psychiatry, in growing quarters, is
finally catching up.
Acknowledgements. None.
Financial support. None.
Conflict of interest. None.
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