The recognition of antidepressant discontinuation reactions
http://www.critpsynet.freeuk.com/Recognition.pdf
The recently published clinical guideline on the management of depression from the
National Institute for Clinical Excellence contains advice that patients prescribed
antidepressants should be given a disclaimer about the risk of
discontinuation/withdrawal symptoms.1 By comparison, not so long ago, a key
message of the Defeat Depression Campaign of the Royal Colleges of Psychiatrists
and General Practitioners was that patients should be informed clearly when first
prescribed antidepressants that discontinuing treatment in due course will not be a
problem.2 Furthermore the general public were criticised in the campaign for
believing that antidepressants are addictive.
Although the debate about whether antidepressant discontinuation reactions amount to
evidence of dependence may be largely semantic, there is a general perception that
withdrawal reactions are indicative of dependence.3 However, the presence of a
withdrawal state is neither sufficient nor necessary for a diagnosis of dependence in
the current International Classification of Diseases (ICD-10). Semantic confusion
about discontinuation, withdrawal and relapse can be traced to dissatisfaction with the
definitions of addiction and habituation, leading to the introduction of the single term
'drug dependence' by a World Health Organisation Expert Committee in 1964.4 Since
then, there have been varying shades of meaning of dependence. Developments, such
as the syndromal approach to the diagnosis of drug dependence,5 and
operationalisation of diagnostic criteria to improve diagnostic reliability, have been
incorporated into modern classificatory systems. The Diagnostic and Statistical
Manual of the American Psychiatric Association made tolerance or withdrawal a
required criterion in DSM-III, and in DSM-IIIR dependence was redefined as the
antisocial syndrome of clinically significant behaviours and symptoms indicating loss
of control of substance use and continued use despite adverse consequences.
Case reports of discontinuation reactions have appeared since antidepressants were
first introduced. However, systematic recognition had to wait until a BMJ editorial in
1998.6 Even then the problems were minimised. A few years later the authors of the
editorial updated their views to admit that such reactions are common.7 Some of the
pharmaceutical companies may not have helped scientific debate because of
misleading promotion of their products. For example, GlaxoSmithKline eventually
dropped its insistence that paroxetine is not addictive.8 This is at least partly because
of confusion about the technical and lay definitions of dependence and addiction. A
drug which is thought to improve mood is likely to be habit forming, so however
much the medical profession may declare that antidepressants are not primarily
reinforcing like psychostimulants, the public understand that there may be problems
discontinuing antidepressants.
The earlier distinction between physical and psychological dependence may,
therefore, still have some relevance in clinical practice. People may form attachments
to their medications more because of what they mean to them than what they do.
Psychiatric patients often stay on medications, maybe several at once, even though
their actual benefit is questionable. Any change threatens an equilibrium related to a
complex set of meanings that their medications have acquired. These issues of
reliance on medication should not be minimised, yet commonly compliance with
treatment was reinforced by emphasising that antidepressants are not addictive. The
2
NICE guidelines should eliminate this practice. Antidepressants are often prescribed
in life crises reinforcing defensive mechanisms against overwhelming anxiety, and the
power of the placebo effect should be recognised. As suggestion can play an
important part in initial response to treatment, expectations are as likely to play a role
in withdrawal, producing a nocebo reaction.
The relapse rate in randomised controlled trials of discontinuation of antidepressant
treatment is substantial.9 Discontinuation reactions may be confused with relapse, and
may also trigger or be a sign of potential relapse. There is also evidence of a loss of
benefit emerging with long-term treatment and also on retreatment after
discontinuation of antidepressants.10 There is some naturalistic evidence to support
the view that people treated without antidepressants may do better over the long term.
The possibility that antidepressants may, therefore, create a vulnerability to relapse
needs to be taken seriously.11
Even in short-term trials SSRIs do not apparently work that much better than
placebo.12 More evidence is needed from longer-term controlled studies to assess
whether patients who work through their difficulties without medication have a better
outcome over the longer term. Besides the methodological difficulties of testing this
hypothesis, there will be ideological barriers to considering it. However, the lessons
of the history of the resistance to the recognition of antidepressant discontinuation
reactions should help create a more open attitude to examination of this important
issue.
(I declare that the answer to the questions on your competing interest form
(http://bmj.com/cgi/content/full/317/7154/291/DC1) are all No and therefore have
nothing to declare)
1. National Institute for Clinical Excellence. Management of depression in
primary and secondary care. (Clinical guideline 23) London: NICE 2004
2. Priest RG, Vize C, Roberts A, Roberts M, Tylee A. Lay people's attitude to
treatment of depression: results of opinion poll for Defeat Depression
Campaign just before its launch. BMJ 1996; 313: 858-859 [Abstract/Free
Full Text].
3. Russell MAH. What is dependence? In Drugs and drug dependence. (Eds. G
Edwards et al). Saxon House: Westmead, 1976
4. World Health Organization Expert Committee on Addiction-producing Drugs:
Thirteenth report. Geneva: WHO, 1964
5. Edwards G. Nomenclature and classification of drug- and alcohol-related
problems: a WHO memorandum. Bull WHO 1981; 59: 225-42
6. Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions.
Are preventable and simple to treat. BMJ 1998; 316: 1105-6
7. Young A, Haddad P. Discontinuation symptoms and psychotropic drugs.
Lancet 2000; 355:1184
8. Boseley S. Seroxat maker abandons 'no addiction' claim. The Guardian, 3
May 2003 [Full text]
http://www.critpsynet.freeuk.com/Recognition.pdf
The recently published clinical guideline on the management of depression from the
National Institute for Clinical Excellence contains advice that patients prescribed
antidepressants should be given a disclaimer about the risk of
discontinuation/withdrawal symptoms.1 By comparison, not so long ago, a key
message of the Defeat Depression Campaign of the Royal Colleges of Psychiatrists
and General Practitioners was that patients should be informed clearly when first
prescribed antidepressants that discontinuing treatment in due course will not be a
problem.2 Furthermore the general public were criticised in the campaign for
believing that antidepressants are addictive.
Although the debate about whether antidepressant discontinuation reactions amount to
evidence of dependence may be largely semantic, there is a general perception that
withdrawal reactions are indicative of dependence.3 However, the presence of a
withdrawal state is neither sufficient nor necessary for a diagnosis of dependence in
the current International Classification of Diseases (ICD-10). Semantic confusion
about discontinuation, withdrawal and relapse can be traced to dissatisfaction with the
definitions of addiction and habituation, leading to the introduction of the single term
'drug dependence' by a World Health Organisation Expert Committee in 1964.4 Since
then, there have been varying shades of meaning of dependence. Developments, such
as the syndromal approach to the diagnosis of drug dependence,5 and
operationalisation of diagnostic criteria to improve diagnostic reliability, have been
incorporated into modern classificatory systems. The Diagnostic and Statistical
Manual of the American Psychiatric Association made tolerance or withdrawal a
required criterion in DSM-III, and in DSM-IIIR dependence was redefined as the
antisocial syndrome of clinically significant behaviours and symptoms indicating loss
of control of substance use and continued use despite adverse consequences.
Case reports of discontinuation reactions have appeared since antidepressants were
first introduced. However, systematic recognition had to wait until a BMJ editorial in
1998.6 Even then the problems were minimised. A few years later the authors of the
editorial updated their views to admit that such reactions are common.7 Some of the
pharmaceutical companies may not have helped scientific debate because of
misleading promotion of their products. For example, GlaxoSmithKline eventually
dropped its insistence that paroxetine is not addictive.8 This is at least partly because
of confusion about the technical and lay definitions of dependence and addiction. A
drug which is thought to improve mood is likely to be habit forming, so however
much the medical profession may declare that antidepressants are not primarily
reinforcing like psychostimulants, the public understand that there may be problems
discontinuing antidepressants.
The earlier distinction between physical and psychological dependence may,
therefore, still have some relevance in clinical practice. People may form attachments
to their medications more because of what they mean to them than what they do.
Psychiatric patients often stay on medications, maybe several at once, even though
their actual benefit is questionable. Any change threatens an equilibrium related to a
complex set of meanings that their medications have acquired. These issues of
reliance on medication should not be minimised, yet commonly compliance with
treatment was reinforced by emphasising that antidepressants are not addictive. The
2
NICE guidelines should eliminate this practice. Antidepressants are often prescribed
in life crises reinforcing defensive mechanisms against overwhelming anxiety, and the
power of the placebo effect should be recognised. As suggestion can play an
important part in initial response to treatment, expectations are as likely to play a role
in withdrawal, producing a nocebo reaction.
The relapse rate in randomised controlled trials of discontinuation of antidepressant
treatment is substantial.9 Discontinuation reactions may be confused with relapse, and
may also trigger or be a sign of potential relapse. There is also evidence of a loss of
benefit emerging with long-term treatment and also on retreatment after
discontinuation of antidepressants.10 There is some naturalistic evidence to support
the view that people treated without antidepressants may do better over the long term.
The possibility that antidepressants may, therefore, create a vulnerability to relapse
needs to be taken seriously.11
Even in short-term trials SSRIs do not apparently work that much better than
placebo.12 More evidence is needed from longer-term controlled studies to assess
whether patients who work through their difficulties without medication have a better
outcome over the longer term. Besides the methodological difficulties of testing this
hypothesis, there will be ideological barriers to considering it. However, the lessons
of the history of the resistance to the recognition of antidepressant discontinuation
reactions should help create a more open attitude to examination of this important
issue.
(I declare that the answer to the questions on your competing interest form
(http://bmj.com/cgi/content/full/317/7154/291/DC1) are all No and therefore have
nothing to declare)
1. National Institute for Clinical Excellence. Management of depression in
primary and secondary care. (Clinical guideline 23) London: NICE 2004
2. Priest RG, Vize C, Roberts A, Roberts M, Tylee A. Lay people's attitude to
treatment of depression: results of opinion poll for Defeat Depression
Campaign just before its launch. BMJ 1996; 313: 858-859 [Abstract/Free
Full Text].
3. Russell MAH. What is dependence? In Drugs and drug dependence. (Eds. G
Edwards et al). Saxon House: Westmead, 1976
4. World Health Organization Expert Committee on Addiction-producing Drugs:
Thirteenth report. Geneva: WHO, 1964
5. Edwards G. Nomenclature and classification of drug- and alcohol-related
problems: a WHO memorandum. Bull WHO 1981; 59: 225-42
6. Haddad P, Lejoyeux M, Young A. Antidepressant discontinuation reactions.
Are preventable and simple to treat. BMJ 1998; 316: 1105-6
7. Young A, Haddad P. Discontinuation symptoms and psychotropic drugs.
Lancet 2000; 355:1184
8. Boseley S. Seroxat maker abandons 'no addiction' claim. The Guardian, 3
May 2003 [Full text]
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