Epa guidance on tobacco dependence and strategies for smoking cessation in people with mental illness
Available online at
EPA Guidance on tobacco dependence and strategies for smoking
cessation in people with mental illness
T. Ru¨ther ,J. Bobes , M. De Hert T.H. Svensson K. Mann , A. Batra
P. Gorwood H.J. Mo¨ller
a Department of Psychiatry, Ludwig Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany
b Department of Medicine, Psychiatry Area, University of Oviedo, Centro de Investigacio´n Biome´dica en Red de Salud Mental, Cibersam, Oviedo, Asturias, Spain
c University Psychiatric Centre Catholic University Leuven, Campus Kortenberg, Department Neuroscience KU Leuven, Leuvensesteenweg 517, 3070
Kortenberg, Belgium
d Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institute, Stockholm, Sweden
e Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
f Department of Psychiatry and Psychotherapy, Section for Addiction Medicine and Research, University Hospital of Tu¨bingen, Tu¨bingen, Germany
g Sainte-Anne Hospital (CMME), University Paris-Descartes, Paris, France
Tobacco dependence is the most common substance use disorder in adults with mental illness. The
Received 31 December 2011
prevalence rates for tobacco dependence are two to four times higher in these patients than in the general
Received in revised form 13 November 2013
population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental
Accepted 13 November 2013
health patients, and remains the leading preventable cause of death in this group. Despite these statistics,
Available online 30 January 2014
in some countries smokers with mental illness are disadvantaged in receiving intervention and support
for their tobacco dependence, which is often overlooked or even tolerated. This statement from the
European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco
dependence and withdrawal in patients with mental illness and their treatment. It provides seven
Tobacco use cessation
recommendations for the core components of diagnostics and treatment in this patient group. These
Tobacco dependence
recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling
specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7)
Affective disorders
relapse prevention. They aim to help clinicians improve the care, health and well-being of patients
suffering from mental illness.
ß 2013 Elsevier Masson SAS. All rights reserved.
disorder . On the basis of these rates, mental illnesses
represent 47% of the attributable risk of tobacco dependence.
Tobacco dependence is the most common substance use
Smoking has a strong, negative influence on the life expectancy
disorder in adults with mental illness and has prevalence
and quality of life of mental health patients . Tobacco
rates two to four times higher than in the general population
use is the leading preventable cause of death in patients with
. People with severe mental illness (SMI) are often heavy
psychiatric illness or addictive disorder It is also an
smokers. For example, people with schizophrenia tend to smoke
important factor when managing these patients' significantly
more cigarettes a day and inhale the cigarette smoke more deeply
increased risk for cardiovascular disease and diabetes . Studies
than smokers in the general population People with
have found that tobacco-associated cardiac and pulmonary
mental illness (meet DSM-III-R or DSM-IV criteria) make up 44% to
illnesses and cancer are more common among people with a
46% of the North American tobacco market, i.e. in the USA, almost
mental illness and life expectancy in general is reduced
every second cigarette is smoked by someone with a mental
by 25 years in patients with mental illness, mainly because of
chronic diseases related to tobacco use By comparison, in
smokers without psychiatric comorbidity life expectancy is
reduced by 10 years Smoking also predicts suicidal behaviour
independent of the presence of a mental illness
* Corresponding author. Tel.: +49 89 5160 5707; fax: +49 89 5160 5809.
Tobacco-associated diseases are responsible for 6% to 14%
E-mail addresses:
(T. Ru¨ther).
of personal health costs worldwide In
0924-9338/$ – see front matter ß 2013 Elsevier Masson SAS. All rights reserved.
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
addition to the costs for the health systems, the individual costs for
to smoking. Ideally clinicians should have received specialist
the mental health patient also have to be considered: a study found
training as ‘‘tobaccologists''. In reality few have and so conse-
that in the USA patients suffering from schizophrenia spent a
quently, this paper aims to help those who have not received
median of US$142.50 (range $57.15–$319.13) per month on
specialist training to feel confident in treating patients using
cigarettes, corresponding to 27.4% of the median monthly income
evidence-based medicine. The active, guideline-based diagnostics
of this population, the majority of whom were receiving public
and treatment of tobacco dependence should always be part of the
assistance .
care for patients with mental illness.
The motivation to quit is as high among psychiatric patients as
This position statement was developed by the EPA, based on a
in the general population and the distribution of
review of the evidence that patients with SMI are at serious
the stages of motivation to quit smoking in psychiatric samples, as
increased risk of smoking. The aim of this statement is to give
measured by the stages of change model , parallels that for
recommendations for evidence-based diagnostics and treatment of
the general population This is also the case in patients with
tobacco dependence that will allow psychiatrists and primary care
dependence disorders in general .
clinicians to improve the health and well-being of mentally ill
Currently, too little attention is paid to the topic of smoking and
tobacco dependence in everyday psychiatric care. In a retro-
spective study on the prevalence of smoking cessation pro-
derived from current scientific evidence (by means of a systematic
grammes in psychiatric settings, Prochaska et al. found that none of
literature search – detailed below) in addition to expert experience
the 250 psychiatric patients studied were diagnosed with tobacco
and consensus. This position statement was developed by the EPA
dependence and smoking status was not included in the treatment
in accordance with the available international guidelines on
plan . At discharge, only one patient was advised to stop
tobacco withdrawal
smoking, referred for smoking cessation counselling or given
This statement aims to summarise the current knowledge about
tobacco withdrawal treatment. Another study, by the same
tobacco dependence and withdrawal in patients with mental illness
research group, found 52% of the psychiatric patients studied
and to give recommendations for the core components of
reported never having been encouraged by hospital staff to quit
diagnostics and treatment in this patient group. Please note that
smoking Psychiatric patients who smoke appear to have
this statement uses the term ‘tobacco dependence' rather than
poorer access to health care: Himmelhoch et al. showed that
‘nicotine dependence' because we can not rule out the complex
schizophrenia patients who smoked and had type 2 diabetes were
interaction of biological and psychological factors in smoking
less likely to receive services and treatments known to improve
cardiovascular outcomes .
A recent systematic review and quality assessment of guide-
2. Who is at risk and why?
lines/recommendations published between 2000 and 2010 for
cardiovascular risk in patients with schizophrenia shows that
Sociodemographic variables such as sex and employment
smoking cessation is recommended in only half of the evaluated
status appear to be similar in smoking and non-smoking
guidelines .
psychiatric patients. However, considerable differences can be
Meta-analyses on smoking cessation have shown the large
found in age, marital status, psychiatric diagnosis and substance
benefit of smoking cessation measures conducted by physicians
abuse history Younger patients are more likely to smoke
and nursing staff, in particular that of just giving simple advice
than older patients; smoking rates are higher among single
However, none of the studies included in these
psychiatric patients than among married or divorced patients; and
meta-analyses were conducted in a psychiatric setting. One large,
patients with a psychotic illness, bipolar disorder, depression or
multi-centre study looked at implementing the 5 A's (Ask, Advise,
substance use disorder are significantly more likely to smoke than
Assess, Assist, Arrange) for people with SMI attending appoint-
patients with other diagnoses . Over 70% of patients who
ments at community mental health centers. Although no
take illegal drugs or suffer from alcoholism have
significant difference was found at 6 months, by 12 months
been found to be smokers. In fact, the prevalence of tobacco
increased abstinence and smoking reduction were reported
dependence is higher in patients of almost all psychiatric
Despite the high rates of smoking among psychiatric patients,
diagnostic groups . The scope of this paper sets out to cover
hardly any studies have been conducted in Europe in this group of
the treatment of patients with schizophrenia, affective disorder or
patients. Although this topic appears to have been better
substance use disorder. These major disease entities will be
investigated in the USA , still relatively few studies have been
considered in more detail below.
performed compared to the numbers in other areas of smoking
2.1. Schizophrenia
Although a small study of 17 alcohol or drug using schizo-
phrenia patients suggested an inverse correlation in prodromal
In North America, 44% to 88% of schizophrenia patients in
symptom distress and nicotine use , increasing evidence
clinical and population-based
shows that smokers with psychiatric comorbidity can be helped to
samples were found to smoke, compared with 29% of the general
quit smoking without jeopardizing their mental health recovery
population .
In view of the gain in life years and quality of life as well
Schizophrenia patients who smoke have higher blood levels of
as of the favourable cost-benefit ratio, the treatment of tobacco
cotinine than smokers without psychiatric comorbidity, indicating
dependence is one of the most important interventions for
a higher level of consumption or deeper inhalation The
psychiatric in- and outpatients. Tobacco withdrawal programmes
number of cigarettes consumed daily in this patient group
should not be withheld from patients with mental illness. Rather,
special emphasis should be placed on this patient group because
and also with the occurrence of prodromal symptoms
they have pre-existing disadvantages in obtaining health care.
of schizophrenia People with schizophrenia who had
Psychiatrists and primary care physicians need to play an active
lower functioning were also found to smoke more cigarettes per
role in ensuring that patients with mental illness are not put at a
day More than 60% of schizophrenia patients start smoking
disadvantage Addiction is an integral part of
before the first clinical manifestation of the disease and before any
psychiatry training and the general principles learnt also apply
treatment with antipsychotics
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
A 13-year follow-up study in 370 patients with schizophrenia
2.2. Affective disorders
found that fatal, tobacco-associated diseases occurred significantly
more often than in the general population . Life expectancy
The prevalence of tobacco dependence in clinical samples of
was found to be 20% lower in schizophrenia patients and, besides
patients with major depression and population-
other lifestyle habits, smoking was identified as one of the most
based samples of patients with clinically significant depressive
important risk factors for this high mortality . Bobes et al.
symptoms is 40% to 60% higher than in the general population,
showed that if schizophrenia patients at high/very high risk (above
but not quite as high as among schizophrenia patients or patients
10%) of experiencing a cardiovascular event in the subsequent
with a dependence disorder. In the case of patients with bipolar
10 years would stop smoking they would benefit from a near 90%
disorder, Garcı´a-Portilla et al. found that tobacco use was
reduction in risk .
associated with an increased risk of coronary heart disease and
In humans, nicotine enhances motor ability, attention and
that this risk was reduced dramatically to 10% in those who quit
memory. This almost certainly has implications for the initiation of
smoking In a study performed in over 3200 people, Glassman
smoking and maintenance of tobacco dependence even more
et al. showed that 74% of all patients who had experienced a
so for those with mental illness Detailed consideration to the
depressive episode at some time in their lives had a history of
neurobiological mechanisms of nicotine addiction is beyond the
smoking The relationship between tobacco consumption
scope of this paper but Stolerman and Shoaib present a solid
and depressive disorders appears to be reciprocal smoking
review Of central importance in the pathophysiology of
appears to increase the risk for a depressive episode and
schizophrenia is the influence of nicotine on dopaminergic and
the depression appears to sustain the tobacco dependence, as
glutamatergic receptor systems The interaction between
shown by the finding that patients have a much harder time
nicotine and the nigrostriatal and mesocorticolimbic dopamine
quitting, require more attempts before they quit and show more
systems, which are known to be involved in this disorder, has been
side effects from quitting . The main biological
well studied. Chronic nicotine intake may have a positive influence
hypothesis for these effects is probably the direct antidepressive
on the assumed dissociation in schizophrenia between cortical
effect of nicotine or other components in tobacco smoke via
hypoactivity and subcortical hyperactivity In addition to its
inhibition of the monoaminooxidases MAO-A and MAO-B
known dopaminergic effect, nicotine also stimulates glutamate
. Direct cholinergic effects of nicotine also influence
release in the hippocampus . The modulation of these two
cognition, attention and arousal, motivated behaviour and satiety
important neurotransmitters, both of which are involved in the
(for a review see ). In addition, chronic nicotine intake
pathogenesis of schizophrenia, could play a role in the increased
appears to have serotonergic effects via an influence on 5HT
use of nicotine by schizophrenia patients, for example in the form
autoreceptors Animal models (forced swimming test,
models of learned helplessness) have indicated that both acute and
Nicotine has been described to have positive effects on the
chronic nicotine administration also have a direct antidepressive
negative symptoms of schizophrenia : it increases drive and
effect In addition to biological and pathophysiolo-
improves cognitive function Schizophrenia patients with a
gical effects, a large number of behavioural antidepressive effects
high level of negative symptoms are at particular risk of being
of smoking play an important role in the difficulties of depressed
heavier smokers . Ziedonis et al. found more positive
patients in attaining and maintaining abstinence .
symptoms but fewer negative symptoms in smokers than in
The prevalence of smoking is also higher (51% to 70%) in
non-smokers; heavy smokers had the highest positive and lowest
patients with bipolar disorder than in the general population
negative symptom scores Nicotine improves the deficits of
Corvin et al. showed a possible
schizophrenia patients in cognition (sensory gating)
association between smoking and psychotic symptoms in bipolar
working memory and attentional deficits , so that
disorder, although results of other studies are inconsistent
strong self-medication effects can be assumed for these deficits as
Some more recent studies indicate a relationship between smoking
well. Indeed, the nicotinic acetylcholine receptor agonist vareni-
and suicidality in this patient group
cline, which was specifically developed for smoking cessation, has
Studies indicate that patients report no worsening of depressive
been shown to improve cognitive impairments in people with
symptoms following smoking cessation or even
schizophrenia and possesses a unique treatment profile on
improved symptoms but that failed attempts do
core schizophrenia-related biomarkers
Long-term cessation rates are lower for smokers with current
The relationship between smoking and treatment with anti-
depressive symptoms (14%) than for those with a history of
psychotic medication definitely plays an important role in this
depression (22%)
patient group: chronic nicotine intake can improve neuroleptic-
induced extrapyramidal symptoms and reduce the
2.3. Substance use and dependence disorders
occurrence and severity of parkinsonism Furthermore, it
appears that the prevalence of smoking is somewhat lower among
More than 75% of all patients with dependence disorders have
patients treated with modern antipsychotics . Tobacco smoke
comorbid tobacco dependence . The health consequences of
increases the clearance of many antipsychotic drugs (see Section
tobacco and other drug use are synergistic and estimated to be 50%
Smoking and psychopharmacologic medication below), which
greater than the sum of each individually . Thus, smoking and
results in lower plasma levels and can reduce the severity of side
not alcohol is the leading cause of death in patients who have
effects (e.g. extrapyramidal motor symptoms, sedation) and hence
undergone alcohol withdrawal treatment and is responsible for
increase the tendency for patients to smoke more .
more than 50% of all deaths in this patient group
Besides biological and physiological factors, behavioural
Recognising the importance of this small field of research, the
aspects are relevant for the high level of tobacco dependence
Cochrane Collaboration has recently published a study protocol
among schizophrenia patients, e.g. strategies for coping with
aiming to address tobacco cessation interventions specifically in
boredom and the lack of a smoke-free hospital environment
alcohol and drug abuse populations . Alcohol-dependent
Last but not least, in the USA, internal documents of the
patients report greater problems in quitting smoking than non-
tobacco industry were released showing that the industry made a
alcohol-dependent smokers and a higher degree of
multitude of direct and indirect efforts to slow down the reduction
dependence than smokers without a comorbid dependence
of smoking prevalence among people with schizophrenia .
disorder Addressing heavy-drinking in smokers results in
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
better smoking cessation rates . In a 24-year study of long-
ICD-10 defined diagnosis, therapeutic intervention should be paid
term drug abusers, the death rate among cigarette smokers was
for by the healthcare system. However, in many European
found to be four times that of non-smokers .
countries the health insurance companies reimburse smoking
Provision of smoking cessation treatment in conjunction with
cessation treatment (although rarely for any pharmacological
substance use treatment is currently not standard practice due, in
intervention) since they recognise how cost-effective it is. In the
part, to unfounded concern that combining smoking cessation
UK the NHS provides smoking cessation programmes at an
treatment with substance use treatment could lead to poorer
estimated cost of 209 GBPs per patient . Although the cost
outcomes. Treatment of tobacco dependence does not jeopardize
for psychiatric patients is not available, it is likely to be lower as
alcohol abstinence in fact, it is associated with enhanced
these patients have frequent appointments for the management of
sobriety from alcohol and other drugs .
their illness that could simultaneously address the smoking
Both ethanol and nicotine appear to interact with the
dopaminergic reward system whereby the rewarding effect
of alcohol is intensified by nicotine and vice versa . On
the molecular level there are indications that both nicotine and
alcohol have similar effects on the cholinergic, glutamatergic and
4.1. Guidance development process
opioid systems . The prevalence of smoking is also much
higher in patients with opiate or cannabis dependence or cocaine
The EPA developed the European Guidance Project (EGP) in
consumption than in the general population
order to provide a series of guidance papers on a range of topics
within mental healthcare, centered on evidence-based medicine
3. Patient setting
For this guidance document, the EGP's Steering Group
appointed Pr. H.J. Mo¨ller as the lead author, who as such was
3.1. Smoke-free psychiatric wards
responsible for recruiting further experts to develop the document
conceptually and methodologically. It was then written and, before
A few years ago, smoking was banned in hospital buildings and
publication, jointly edited by all co-authors. The final version of
in some hospital grounds in most American states and in many
this position statement was reviewed and endorsed by the EGP
European countries. This ban aims to reduce the dangers of passive
coordinator [Pr. W. Gaebel].
smoking among patients, employees and visitors and to encourage
people to quit smoking. However, generally psychiatry depart-
4.2. Systematic literature search
ments were excluded from this ban because mentally ill patients
were thought to need to smoke in order to manage their
We performed a systematic literature search based on the
psychiatric symptoms. Furthermore, a smoking ban is generally
methods previously published by the EPA as outlined in
presumed to be extremely difficult to enforce in these patients.
Practical experience from smoke-free psychiatric wards has
A total of 4241 potentially relevant citations were identified in
shown, however, that this assumption is unjustified The
PubMed using the Medical Subject Headings (MeSH) ‘‘Mental
changeover to a smoke-free ward proves to be less difficult than
Disorders'' AND ‘‘Tobacco Use Cessation'' as the strategy. Articles
expected, with studies finding no increases in aggression,
were excluded if they did not fulfill the following criteria: (1) listed
disruption, discharges against medical advice, use of medications
as a Meta-Analysis, Randomized Controlled Trial OR systematic
or restraints or admission refusal, even in acute or closed
review under publication type, (2) published in English OR German
psychiatric settings . Prochaska reported a high interest
language and (3) published between January 2008 and March
and uptake (79%) of tobacco cessation treatment in inpatient
psychiatry patients .
Additionally, we screened The Cochrane Tobacco Addiction
In a study of 322 smokers suffering from depression, no
Group's specialized register (currently stands at 82 reviews). This
detriment to mental health was found among individuals who quit
register contains reports of trials on tobacco addiction interven-
smoking as compared to those who continued to smoke after
tions identified from The Cochrane Central Register of Controlled
inpatient smoking cessation . Furthermore, on psychiatric
Trials (CENTRAL), MEDLINE, EMBASE and PsycInfo. One author
wards that have voluntarily banned smoking, changes have been
(T. Ru¨ther) screened the remaining 405 abstracts and all of the
seen in the patients' attitude to smoking: their desire to quit
smoking and their confidence in being successful were positively
abstracts for relevance. Of these, 427 citations were excluded as
influenced by the smoke-free environment .
irrelevant for this statement (for example study protocols,
adolescent or pregnant populations, duplicate studies). Further
3.2. Inpatient vs. outpatient treatment
articles were identified by cross searching reference lists of highly
relevant papers.
Smoking cessation treatment should be offered in both the
inpatient and outpatient setting. The evidence-based treatment
advice laid out in this document can be implemented in either
5. Guidelines for screening and monitoring smoking cessation
Although most studies into smoking cessation in patients with
The available guidelines on smoking cessation in general,
mental illness were carried out in an outpatient setting, Prochaska
prepared by national and international groups
presents a convincing ‘‘10-reason'' report supporting inpatient
present good evidence-based and practice-oriented information
cessation treatment . Most recently, Prochaska et al. con-
for smoking cessation and also consider the treatment of patients
ducted the first randomized controlled trial evaluating the efficacy
with psychiatric comorbidity. However, the need for research in
of inpatient treatment and reported a decreased re-hospitalization
this patient group is made clear by the fact that the guidelines
include hardly any concrete instructions or programmes for such
There is a huge difference in how European countries approach
patients. The most detailed consideration of the treatment of
tobacco control and treatment. Since nicotine dependence is an
smoking in psychiatric patients can be found in the guidelines on
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
Fig. 1. A flow scheme of the literature search performed for this statement paper.
smoking cessation from the American Psychiatric Association
edition (DSM-IV) classify addiction to smoking as a mental
(APA) although the APA notes that most of its recommenda-
disorder. DSM-IV uses the term ‘nicotine dependence' and thus
tions are derived from experience in smokers without psychiatric
emphasises nicotine as the substance causing the dependence.
comorbidity because few useful studies have been performed in
ICD-10, on the other hand, justifies using ‘tobacco dependence' by
patients with mental illness.
saying that dependence on nicotine is not possible without
consuming tobacco and that it has not yet been clearly demon-
6. Assessment of tobacco dependency
strated that nicotine is the only substance in tobacco smoke that
causes dependence
6.1. Tobacco/nicotine dependence as classified in ICD-10 und DSM-IV
The classification systems specify very similar definitions and
criteria for dependence on smoking. At least 3 of 6 (ICD-10) or 7
The two main diagnostic classification systems, the Interna-
(DSM-IV) criteria have to have occurred within the previous
tional Classification of Diseases, tenth revision (ICD-10) and
12 months to allow a diagnosis of dependence. The diagnostic
the Diagnostic and Statistical Manual of Mental Disorders, fourth
criteria of the two systems are shown in .
Diagnostic criteria for tobacco/nicotine dependence according to ICD-10 and DSM-IV.
ICD-10 – Tobacco dependence syndrome
DSM-IV -Nicotine dependence
Definition: A cluster of physiological, behavioural, and cognitive phenomena in which the
Definition: A maladaptive pattern of substance use, leading to
use of tobacco takes on a much higher priority for a given individual than other behaviours
clinically significant impairment or distress
that once had greater value. A central descriptive characteristic of the dependence syndrome
is the desire (often strong, sometimes overpowering) to take tobacco
A definite diagnosis of dependence should usually be made only if three or more of the
Three (or more) of the following criteria must have occurred at
following have been experienced or exhibited at some time during the previous year:
any time in the same 12-month period:
1. A strong desire or sense of compulsion to take tobacco
1. Nicotine is often taken in larger amounts or over a longer period
than was intended
2. Difficulties in controlling tobacco-taking behaviour in terms of its onset, termination,
2. There is a persistent desire or unsuccessful efforts to cut down or
control substance use
3. A physiological withdrawal state when tobacco use has ceased or been reduced, as evidenced
3. Withdrawal: (a) the characteristic withdrawal syndrome for
by: the characteristic withdrawal syndrome for tobacco; or use of the same (or a closely
nicotine or (b) nicotine is taken to relieve or avoid withdrawal
related) substance with the intention of relieving or avoiding withdrawal symptoms
4. Evidence of tolerance, such that increased doses of tobacco are required in order to achieve
4. Tolerance: (a) a need for a markedly increased amount of nicotine
effects originally produced by lower doses
to achieve intoxication or the desired effect or (b) markedly
diminished effect with continued use of the same amount
5. Progressive neglect of alternative pleasures or interests because of tobacco use, increased
5. Important social, occupational, or recreational activities are given
amount of time necessary to obtain or take the substance or to recover from its effects
up or reduced because of nicotine use
6. Persisting with tobacco use despite clear evidence of overtly harmful consequences, such as
6. Nicotine use is continued despite knowledge of having a persistent
depressive mood states consequent to periods of heavy substance use, or drug-related
or recurrent physical or psychological problem that is likely to have
impairment of cognitive functioning; efforts should be made to determine that the user was
been caused or exacerbated by nicotine
actually, or could be expected to be, aware of the nature and extent of the harm
7. A great deal of time is spent in activities necessary to obtain
nicotine, use nicotine or recover from its effects
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
Criteria relating to the amount of time spent obtaining, using or
These two questions alone can account for up to 6 of the total
recovering from use of the substance and the reduction of time
of 10 points.
spent on important activities because of using the substance are
As a measurement of the severity of physical dependence, the
not only important in the dependence of substances, such as
FTND correlates well with the carbon monoxide content of exhaled
heroin, they also have a role in tobacco dependence. However, the
air, the nicotine and cotinine plasma levels and physiological
criteria for withdrawal symptoms, continued use despite harmful
parameters during the first days of abstinence such as heart rate
consequences and reduced control of amount used are key for
and body and skin temperature The sum score of the FTND is
diagnosing the disorder.
one way of assessing the probability of becoming abstinent as a
result of a smoking cessation programme. The FTND score allow a
6.2. Tobacco dependence according to the Fagerstro¨m Test for
prognosis to be made about the likelihood of a smoker who wants
Nicotine Dependence
to quit actually becoming abstinent as a result of drug-supported
and behavioural-therapy oriented withdrawal treatment. The type
Both ICD-10 and DSM-IV have separate categories for depen-
and dose of pharmacological therapy in particular is determined by
dent and non-dependent smokers. Such an all-or-nothing
the severity of the tobacco dependence . In summary, in the
approach is unsatisfactory and of little use in everyday clinical
international literature the FTND is deemed to be the gold standard
care because it does not allow treatment plans to be tailored to an
for assessing tobacco dependence.
individual's needs . For this reason, the ‘Fagerstro¨m Test for
Nicotine Dependence' (FTND) has become the internationally
6.3. Nicotine and cotinine levels and carbon monoxide (CO)
accepted and proven approach to describing tobacco dependence
. This test measures the dependence as a dimensional
parameter and represents the severity of the dependence on a
Nicotine and cotinine levels can be measured in blood, saliva
continuum. The FTND assesses the severity of a smoker's physical
and urine. Nicotine levels reflect smoking over the last few hours,
dependence on the basis of six questions, with different answer
whereas cotinine, a metabolite of nicotine, is sensitive to smoking
formats, that are intended to record the construct tobacco
in the past 7 days and thus offers a better measure of total daily
dependence one dimensionally ().
nicotine exposure Carbon monoxide levels can be measured
The FTND is analysed by calculating a sum score, which ranges
in exhaled air with a half-life of 4.5 hours. In practical terms, a cut-
from 0 to 10 points and corresponds to dependence severity, as
off level of 12 ppm can be used to distinguish between recent
follows: very low or no dependence (0 to 2 points); low
smokers and those that have refrained for the past 8 hours
dependence (3 or 4 points); medium dependence (5 points);
The advantages of assessing carbon monoxide are that it can be
and high dependence ( 6 points) The average score in
measured easily and quickly and can be used to verify that a
smokers in the general population is between 2.8 and 5.6 points
patient has quit smoking also when the patient has chosen a
. Smokers who sign up for tobacco withdrawal programmes
nicotine preparation as the concomitant drug therapy. It has also
have significantly higher average FTND scores than average
been suggested that the measurement of carbon monoxide can
consumers: various studies have found that smokers who want
reinforce abstinence by making the success of abstinence visible
to quit smoking have scores between 5.2 and 6.6 points .
The reliability and predictive validity of the FTND has been
proven in several studies . The questions about the
7. Withdrawal symptoms
time of smoking the first cigarette in the morning and the number
of cigarettes smoked per day are considered to be the most stable
Withdrawal symptoms are reported by about half of all smokers
predictors of the severity of dependence and have proven
who try to quit smoking . It is difficult to predict who will
themselves in clinical practice as indicators of high dependence
experience withdrawal symptoms and who will not. If withdrawal
Items and scale values of the Fagerstro¨m Test for Nicotine Dependence (FTND)
American Psychiatric Association (DSM-IV-TR) and World Health Organization
(ICD-10) criteria for nicotine or tobacco withdrawal syndrome .
DSM-IV-TR nicotine
ICD-10 DCR tobacco
1. How soon after you wake up do
you smoke your first cigarette?
Difficulty in concentrating
Dysphoric or depressed mood
Increased appetite or weight gain
Increased appetite
2. Do you find it difficult to refrain
from smoking in places where it is
Irritability, frustration or anger
Irritability or restlessness
forbidden e.g. in church, at the
library, in cinema, etc.?
Decreased heart rate
Craving for tobacco (or other
3. Which cigarette would you hate
The first one in the
Malaise or weakness
4. How many cigarettes/day do
a Also requires ‘‘daily use of nicotine for at least several weeks;'' that symptoms
‘‘cause clinically significant distress or impairment in social occupational, or other
important areas of functioning;'' and that ‘‘symptoms are not due to a general
5. Do you smoke more frequently
medical disorder and not better accounted for by another medical disorder'' .
during the first hours after waking
Also requires ‘‘clear evidence of recent cessation or reduction of tobacco use
than during the rest of the day?
after repeated, and usually prolonged and/or high dose, use of tobacco'' and
‘‘tobacco symptoms and signs are not accounted for by a medical disorder unrelated
6. Do you smoke if you are so ill that
to substance use, and not better accounted for by another mental or behavioural
you are in bed most of the day?
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
Smoking 7–12 cigarettes daily is sufficient for the maximum
Important psychotropic medications with smoking-induced metabolism (modified
induction of clozapine and olanzapine metabolism . There
are many reports of intoxications during clozapine or olanzapine
treatment after smoking cessation so it is advisable to
monitor blood levels of clozapine and reduce the dose when
patients quit smoking Therapeutic drug monitoring and
recording of both smoking status and history of previous or
planned attempts at quitting smoking should generally be an
essential part of treatment with the above-mentioned psycho-
9. Treatment of tobacco dependence
v: variable.
The primary objective of every tobacco withdrawal treatment is
long-term cessation of smoking. Initial goals include moving
smokers from not contemplating smoking cessation to contem-
symptoms occur they manifest themselves as physical symptoms,
plating cessation to initiating a quit attempt to stop smoking for a
such as palpitations or low blood pressure, and also in particular as
short period . Data on reduced smoking, i.e. a reduction in the
psychovegetative and psychological reactions such as anxiety,
number of cigarettes smoked daily, are inconsistent
concentration difficulties, sleep disorders, feelings of hunger,
Although it seems health benefits are unlikely (perhaps due to
irritability, restlessness, weight gain, negative affect and strong
compensatory smoking), it may have a valuable role as a step
craving for cigarettes . shows a
toward smoking cessation particularly in some psychiatric
comparison of the common withdrawal symptoms described in
diagnostic groups, e.g. in schizophrenia patients or patients with
the ICD-10 and DSM-IV. Withdrawal symptoms appear as early as a
a substance use disorder
few hours after stopping smoking and peak after 24 to 48 hours.
The first version of the US Department of Health and Human
Normally they markedly decrease or disappear within one week to
Services guideline on treating tobacco withdrawal recom-
10 days Craving and feelings of hunger or increased appetite
mended that psychiatric patients who smoke should receive the
have also been reported over a period of 6 months and longer, as
same treatment for tobacco dependence as smokers in the general
have depressed mood and clinically relevant depressions
population. At the time of completion of this guideline, hardly any
. Studies have found that the degree of withdrawal
studies had been performed on tobacco withdrawal in a
symptoms is independent of the number of cigarettes smoked
psychiatric setting so recommendations were derived and
daily before the withdrawal and that after partial withdrawal the
generalised from those for the general population . The
symptoms are often more severe than after complete cessation,
guideline was updated in 2008 and highlighted the value of
which may speak against a solely pharmacological process through
treating smokers with mental illness. However, even the updated
the substance nicotine. Withdrawal symptoms frequently occur as
version does not clarify whether or not interventions need to be
a result of triggering stimuli and can thus also be explained as the
tailored to particular disorders. The few studies performed in a
result of a conditioning process
psychiatric setting did find that treatments developed for the
Distinguishing between withdrawal symptoms, such as anxi-
general population produced higher abstinence rates than
ety, depression, increased REM sleep, insomnia, irritability, rest-
placebo or other control treatments, although the overall
lessness and weight gain, and symptoms arising from the
abstinence rates in both psychiatric and substance use disorder
psychiatric condition can be difficult. Withdrawal symptoms can
treatment populations were lower than in studies performed in
disguise, mimic or aggravate the symptoms of a psychiatric
participants from the general population. The available meta-
disorder and therefore can result in patients falsely
analyses on smoking cessation in depressive patients ,
attributing relief to effects on mental disorders. For example,
schizophrenic patients and patients with a substance use
nicotine replacement reduced agitation in smokers hospitalised for
disorder unanimously demand further research in this area.
schizophrenia by one third . In general, patients with SMI show
We eagerly await the imminent publication by The Cochrane
more frequent and severe withdrawal symptoms after quitting
Collaboration on interventions for tobacco use cessation in people
in treatment for or recovery from substance use disorder and
Momentum is gaining slowly in this field and the data indicate
8. Smoking and psychopharmacological medication
treatments that work in the general population work as effectively
for those with severe mental illness . The APA practice
Smoking has a strong influence on the rate of metabolism of
guideline specifies that smokers with a psychiatric disorder
many psychopharmaceuticals, in particular those metabolized by
require more intensive psychotherapeutic support than smokers
the liver microsomal system of the cytochrome isoform P450 1A2
in the general population and possibly also supportive medication
(). The induction of this enzyme means that serum levels
Prolonging the treatment period has been proposed in this
of many psychopharmaceuticals are lower in smokers than in
population . Nevertheless, treating tobacco dependence in
non-smokers . Stopping smoking may increase the blood
patients with stable psychiatric conditions does not worsen mental
levels of these drugs, which in turn can worsen side effects or
cause toxicity. This effect appears to be due not to nicotine but
The combination of psychotherapeutic techniques and con-
rather to the effects of benzopyrenes (tobacco carcinogens) and
comitant supportive medication is deemed to be the silver bullet in
related compounds on the P450 system . Such effects have
the treatment of tobacco dependence (The
been described as being particularly strong with the drug
objective of combination therapy is to treat possible withdrawal
clozapine: smoking patients need to be administered on average
symptoms after smoking cessation and simultaneously expand
50% higher daily doses than non-smoking patients .
skills for smoke-free behaviour.
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
Effectiveness of and estimated abstinence rates for the combination of counselling and medication alone: results of a meta-analysis (n = 18 studies)
Estimated odds ratio (95% CI)
Estimated abstinence rate (95% CI)
Medication and counselling
27.6 (25.0–30.3)
9.1. Psychopharmacological treatment
sublingual tablets, inhaler, nasal spray, mouth spray) has proven to
be particularly effective. Longer use (for at least 8 weeks) is
Current clinical practice guidelines from the US department of
recommended Most nicotine preparations available in
health on the treatment of tobacco dependence list the following
Europe have been sold for decades as over-the-counter products
drugs, in combination with concomitant counselling, as first-line
(i.e., without a prescription) and have an extremely good safety
treatment: short- or long-acting nicotine replacement therapy
profile. Although the nicotine nasal spray and the inhaler release
(NRT), sustained release bupropion (bupropion SR) and vareni-
nicotine somewhat more quickly than the other routes of
cline. These recommendations were made on the basis of extensive
administration, nicotine absorption is significantly slower with
meta-analyses in which the effectiveness of the drugs 6 months
all routes of administration than with cigarettes and the peak
after smoking cessation was investigated in adults without
nicotine concentration is lower. This phenomenon is probably the
psychiatric comorbidity . The estimated odds ratios 6 months
reason why hardly any cases of dependence on nicotine prepara-
after smoking cessation were 2.2 to 3.8 (95% confidence interval).
tions have been reported . The efficacy of NRT in the
Despite the very good and robust database on the safety and
treatment of smoking in patients with depression is comparable to
efficacy of drug treatment of tobacco dependence, only a few
the general smoking population . In a placebo-controlled,
studies have examined their use in mentally ill patients. These
randomised study, smokers with current depression had a 3-
studies are listed in for reference. To date, research
month cessation rate of 29.5% in those treated with nicotine
supports the hypothesis that smoking cessation interventions used
chewing gum plus counselling compared with 12.5% in those who
in the general smoking population would be also beneficial in
received placebo chewing gum plus counselling . In a follow-
smokers with mental illness.
up study by the same group, the cessation rates at 12 months were
15% in the NRT treatment group and 5.7% in the placebo gum group
9.1.1. NRT (Nicotine replacement therapy)
NRT can be used as first-line therapy for all smokers .
The efficacy of NRT has also been shown in schizophrenia
Currently, seven preparations are available—patch, chewing gum,
lozenge, sublingual tablets, inhaler/inhalator, nasal spray and
mouth spray—although the last two dosage forms are only
Further trials with longer follow-up periods are needed to
available in a few European countries. A pill that could reliably
determine whether extended treatment leads to higher long-term
produce high enough nicotine levels in the central nervous system
cessation rates since one recent study suggests that people
would risk causing adverse gastrointestinal effects. To avoid this
who quit smoking relapse at equivalent rates, regardless of NRT
problem, nicotine replacement products are formulated for
use . This controversial study goes against the general consensus
absorption through the oral or nasal mucosa (chewing gum,
and received plenty of criticism due to its methods
lozenges, sublingual tablets, inhaler/inhalator, nasal and mouth
spray) or skin (transdermal patches)
All routes of administration reduce withdrawal symptoms
effectively and improve the cessation rate among both male and
9.1.2. Bupropion SR
female smokers A combination of a long-acting route of
The sustained release formulation of the antidepressant
administration (patch) with a short-acting one (gum, lozenges,
bupropion (bupropion SR) can also be considered a first-line drug
treatment in patients who smoke. Its efficacy and tolerability
appear to be similar to those of NRT. Treatment with bupropion SR
should commence 7 days before quit day and the dose should be
Overview of studies investigating drug treatment of tobacco dependence in
gradually increased. Primary side effects are headache, jitteriness,
mentally ill patients.
insomnia and gastrointestinal symptoms. Special care needs to be
taken when treating patients who suffer from epileptic seizures of
Evidence available
any kind because epileptic seizures have been observed during
treatment with bupropion.
A few small studies into bupropion use in schizophrenia have
been published (The best indication of its efficacy and
safety comes from a recently updated Cochrane meta-analysis,
which found increased abstinence rates both at the end of
treatment (7 trials, n = 340; risk ratio 3.03; 95% confidence interval
Affective disorders
1.69–5.42) and after 6 months (5 trials, n = 214, risk ratio 2.78; 95%
confidence interval 1.02–7.58). Treatment did not jeopardise
mental state. Bupropion may also reduce the number of cigarettes
these patients smoke
Bupropion is efficacious for smoking cessation in patients with
Substance use disorders
a history of depression or alcoholism . The feasibility of
bupropion has been also indicated in a very small pilot study of
bipolar smokers and in a double-blind, placebo-controlled
trial of opioid-dependent smokers In combination with NRT
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
and counselling, bupropion slightly improves cessation rates in
. In a review, Purvis et al. conclude that for patients with
patients with a history of depression (36% vs. 31% for place-
mental illness, varenicline should be considered safe but that
bo + NRT + counselling) or alcoholism (11% vs. 6% for
attention should be given to treatment initiation, patient educa-
placebo + NRT + counselling) , although not significantly so.
tion and the development of any mood or behavior changes
To date, two double-blind, placebo-controlled trials have been
In a recent study of varenicline, having a history of psychiatric
published on the outcome of patients with schizophrenia on
diagnosis was not associated with worse outcome or side effects
combination therapy. Evins et al. found that patients taking
bupropion + NRT had a significant increase in smoking reduction at
There is now quite a lot of support for the efficacy of varenicline
3 and 6 months (60% vs. 31%; P = 0.036), and a greater continuous
abstinence rate at week 8, (52% vs. 19%; P = 0.014) over patients
as well as case series and case reports
taking placebo + NRT. However, relapse rates were very high
The strongest support comes from two recent randomized, double-
during and after NRT taper and abstinence rates did not differ
blind studies . They both indicate it is both a safe
significantly at 3 months (36% vs. 19%), 6 months (20% vs. 8%) or
treatment for this patient group and also highly effective. Williams
12 months (12% vs. 8%) The other trial of combination therapy
et al. report that at the end of treatment (12 weeks), 16/84
found a significant improvement in smoking abstinence for
varenicline-treated patients (19.0%) met smoking cessation
bupropion + NRT (27.6%) compared with placebo + NRT (3.4%) at
criteria vs. only 2/43 (4.7%) for placebo and this difference was
6-month post quit date .
still significant at 24 weeks: 10/84 (11.9%) vs. 1/43 (2.3%). Adverse
event rates were similar between groups, as were schizophrenia
9.1.3. Varenicline
symptoms, mood and anxiety ratings A systematic review by
Varenicline is a nicotinic acetylcholine partial agonist at the
Cerimele et al. also found that varenicline treatment is not
a4ß2 receptor and full agonist at the a
It was specifically
associated with any exacerbation of psychiatric symptoms in
developed for smoking cessation, aimed at reducing both with-
stable, closely monitored patients with schizophrenia .
drawal symptoms and the rewarding properties of nicotine. In
Less evidence is available on the efficacy of varenicline in
registration studies and the first meta-analyses, varenicline
patients with affective or substance use disorders. In a feasibility
showed few side effects and good long-term abstinence rates.
study, varenicline treatment in three bipolar patients was well
The Cochrane Collaboration conducted a systematic review of
tolerated and associated with reductions in smoking
nicotinic receptor partial agonists for smoking cessation . Their
McClure et al. found in the COMPASS trial that smokers with a
meta-analysis of long-term abstinence data shows that varenicline
history of depression were more likely to report common side
increases the chances of successful long-term cessation over 2-fold
effects associated with varenicline and/or nicotine withdrawal.
and is superior to bupropion (the pooled risk ratios [95% CI] were
However, cessation rates were similar to those published in the
2.27 [14 trials, 6166 people] versus placebo, 1.52 [3 trials, 1622
clinical efficacy trials for varenicline regardless of history of
people] versus bupropion SR and 1.13 [2 trials, 778 people] versus
depression and similar mood and overall side effects were reported
Since varenicline was introduced to the market, there have been
A double-blind, placebo-controlled smoking cessation study in
some reports of exacerbations of symptoms of existing psychiatric
heavy-drinkers found that varenicline produced a sustained
disorders during treatment and some reports of
decrease in alcohol consumption in addition to a significant
psychiatric side effects in patients without a diagnosis of mental
decrease in the number of cigarettes smoked . An open-label,
illness On July 1st, 2009, following alerts and public
pilot study suggests that varenicline may be an effective treatment
health advisories issued by the US FDA, the product labelling and
for tobacco dependence in recovering alcohol-dependent smokers
the prescribing and Medication Guide for varenicline were revised.
. Another pilot study of cocaine using smokers maintained on
Based on the continued review of post-marketing adverse reports,
methadone reported that treatment with varenicline was asso-
they now include a boxed warning highlighting the risk of serious
ciated with a reduction in smoking, even though subjects received
neuropsychiatric symptoms. These symptoms include changes in
only a brief education for smoking cessation . Although no
behaviour, hostility, agitation, depressed mood, suicidal thoughts
adverse events related to medication were reported during these
and behaviour, and attempted suicide. Some of these cases may
studies, large, randomised, placebo-controlled, double-blind clin-
have been confounded by symptoms typically seen in people who
ical studies are needed to assess the use of varenicline in these
have stopped smoking and are experiencing nicotine withdrawal
It should be noted that in one recent study, varenicline use was
A meta-analysis of the available placebo-controlled, rando-
associated with an increased risk of serious adverse cardiovascular
mised, double-blind studies found no increase in psychiatric side
events compared with placebo (odds ratio 1.72, 95% confidence
effects, apart from sleep disorders in patients without an existing
interval) . However, the study received plenty of criticism due
mental illness Indeed the recent Cochrane review concludes
to its limitations . Furthermore, most agree that any
that there is ‘‘little evidence from controlled studies of any link
possible risk is greatly outweighed by the benefits of smoking
between varenicline and psychiatric adverse events'' .
cessation The Cochrane review states that the incidence of
The clinical trials during drug development excluded patients
cardiovascular adverse events remains inconclusive
with active psychiatric illnesses and to date, only a few controlled,
In summary, three effective first-line pharmacological agents,
randomised studies have been published on varenicline use in
which have also been used successfully in some studies in patients
patients with mental illness. In a retrospective comparison of
with psychiatric comorbidity, are available for smoking cessation.
varenicline and NRT for smoking cessation performed at a routine
clinic for tobacco dependence in the UK, varenicline was found to
9.1.4. Adolescent population
be effective in patients with mental illness. Varenicline showed
Only a few trials have looked at smoking cessation in
better efficacy than NRT 4 weeks after quit day. Furthermore, the
adolescents and none specifically in those with mental illness.
side effect profile of varenicline was comparable in patients with
Most tobacco control programmes focus on the prevention of
and without mental illness. In the group treated with varenicline,
uptake as those who do not smoke before the age of 20 are less
no exacerbation of psychiatric symptoms over the 4 weeks of
likely to ever start. Grimshaw and Stanton's Cochrane review
treatment was reported in the patients with existing mental illness
reports that approaches combining behavioural therapies seem
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
most promising . They reviewed three pharmacological trials
available data in this patient group (as discussed in this paper),
(NRT and bupropion) carried out in in adolescent smokers, and
we recommend all patients with schizophrenia, affective disorder
conclude they did not demonstrate effectiveness for long-term
or substance abuse disorder that are in a stable phase of their
abstinence. One of these trials recruited 120 adolescent smokers
condition be treated according to the guidelines for the general
who met criteria for substantial nicotine dependence Three-
population. As always, a psychiatrist must be consulted if the
quarters of these participants had one or more psychiatric
clinician is unsure as to the mental condition of the patient.
diagnoses, reflecting the high rate of co-occurring disorders that
Clinicians should not be afraid to ask patients with mental illness if
characterises the adolescent population of heavy smokers.
they want to stop smoking and if so implement the recommenda-
More high quality trials are needed to identify effective
tions listed below in Section .
intervention, although this remains difficult as, for example, in
A three-phase orientation, as outlined below, is common to all
the UK, NRT is the only smoking cessation medication licensed for
recommendations the preparation of smoking cessation, the
adolescents . To date, there are no published trials of
cessation itself and the stabilisation of smoke-free behaviour. For
varenicline for smoking cessation in adolescents.
all three phases of smoking cessation, specific intervention
Since the Cochrane review, one study found bupropion plus
techniques are available as part of a multi-modal procedure. The
behavioural counselling efficacious, however abstinence rates
programme components such as motivation analysis, skills
were lower than those reported in adults and again, relapse tended
training and relapse prevention should be considered and
to occur soon after the medication was discontinued .
operationalised Just like behaviour-therapy treatments in
the stricter sense, the programme must comply with the treatment
9.2. Psychotherapeutic treatment - Counselling
phases of relationship-shaping, definition of the treatment goal
and the actual training phase.
9.2.1. Short-term treatments
Merely the simple recommendation by a physician to quit
9.2.2.1. Preparation phase. As tobacco dependence is a chronic
smoking significantly increases the long-term cessation rate in
relapsing disorder and most smokers require 5 to 7 attempts before
tobacco-dependent people (
they finally quit for good a therapeutic alliance is required so
The most recent US Department of Health and Human Services
that even after unsuccessful cessation attempts the patient
guideline on treating tobacco withdrawal states: ‘‘All physicians
remains in contact with the treating psychiatrist and continues
should strongly advise every patient who smokes to quit because
treatment. The clarification perspective is also important; the
evidence shows that physician advice to quit smoking increases
patient should hereby become aware of abstinence as the
abstinence rates. (Strength of Evidence = A)'' (p. 82). However,
treatment goal and of his or her own motivational state. The
future studies still have to show whether this finding is
smoker's ambivalence can be expressed and strengthened by
transferable to psychiatric patients. Considering the large number
listing the advantages of smoking and not smoking. First,
of contacts these patients have with a physician, however, this
arguments in favour of smoking are collected, then arguments
simple procedure doubtless has a large effect on public health.
in favour of not smoking. Getting the participant to consciously
Besides this brief intervention, meta-analyses show a direct
decide on the goal of abstinence and collect arguments supporting
relationship between the length of the physician intervention
this decision should resolve any resulting unpleasant cognitive
and the probability of cessation. Even minimal counselling of less
than 3 minutes increases the cessation rate significantly compared
Psychoeducational elements serve to transfer knowledge so
with no-counselling (e.g. self-help manual only) (odds ratio 1.3
that the patient can gradually develop an illness model of his or her
[1.01–1.6]). The cessation rate was further increased by low-
tobacco dependence. A further component of the preparation
intensity counselling of 3 to 10 minutes or intensive counselling of
phase is the diagnostics of the tobacco dependence and smoking
more than 10 minutes (odds ratio 1.6 [1.2–2.0] and odds ratio 2.3
behaviour. The diagnosis of tobacco dependence is confirmed by
[2.0–2.7], respectively). Therefore to improve cessation success,
the FTND; the sum score allows conclusions to be drawn about the
several counselling sessions should be conducted
patient's physical tobacco dependence. Self-observation proce-
The APA recommends that psychiatrists routinely assess a
dures can be used for the diagnostics of smoking behaviour. These
patient's smoking status (e.g., current smoker, ex-smoker, never
procedures include the completion of registration cards for a week
smoked, number of cigarettes per day). A procedure analogous to
and keeping a simple running tally. The aim in every case is that the
the so-called ‘4 A Intervention' is recommended for short-term
smoker observes his or her own smoking behaviour, interrupts the
interventions by physicians: (1) Ask; (2) Advise; (3) Assist; (4)
mechanism of automatic smoking and smokes consciously again.
Arrange. The psychiatrist should thus: (1) ask about the patient's
smoking habits; (2) clearly advise the patient to quit smoking; (3)
9.2.2.2. Smoking cessation. The aim of the second phase is to cease
offer the patient psychological support during smoking cessation
smoking and achieve abstinence. The necessary preparations have
and explain pharmacological aids; and (4) arrange follow-up visits
to be made for the day when the participant ceases to smoke. In the
to check that the patient is still abstinent
abrupt cessation method, a so-called ‘quit day' is set and smoking
behaviour is changed from one day to the next. The participant
9.2.2. Specific treatments
stops smoking on quit day, regardless of the number of cigarettes
The current recommendations in international guidelines on
previously smoked per day. The patient is carefully prepared for
smoking cessation are based mainly on studies that excluded
quit day, and the actual quit day is planned in detail. Differentiated
patients with psychiatric comorbidity. However, given the
skills training should give the participant sufficient competency
Effectiveness of and estimated abstinence rates for advice to quit by physician: results of a meta-analysis (n = 7 studies) .
Estimated odds ratio (95% CI)
Estimated abstinence rate (95% CI)
No advice to quit (reference group)
Physician advice to quit
10.2 (8.5–12.0)
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
and confidence in his or her ability to quit. To achieve this, the cues
contingency management intervention for reducing smoking in
and situations associated with smoking are identified and analysed
schizophrenia and substance use disorder patients
and the patient is advised to avoid possible critical situations on
A meta-analysis on the easy-to-learn, psychotherapeutic
this day; the patient is taught suitable alternative strategies for
technique of ‘motivational interviewing' showed that
dealing with such cues and situations if they cannot be avoided.
shorter, even one-time interventions with this technique, e.g. by
The ‘quit day' approach is the standard way to try to stop
general practitioners, result in higher cessation rates than standard
smoking. However, if this method is unsuccessful, patients may
advice or self-help Further studies are needed to
also gradually reduce the number of cigarettes smoked a day over a
evaluate whether motivational interviewing is similarly effective
longer time period A recent meta-analysis found a
for nicotine withdrawal in psychiatric patients.
comparable abstinence effect between quitting abruptly and
After successful smoking cessation in psychiatric patients,
reducing the number of cigarettes smoked a day before the quit
particular attention should be paid in the further course of
day . Thus, both methods can be recommended. For special
treatment to additional cardiovascular risk factors (e.g. weight,
patient groups, e.g. schizophrenia patients, the reduction of
blood fats, development of diabetes) and respective steps taken if
cigarette consumption may be useful at first as an intermediate
necessary . For example, there are indications that this
goal – see Section .
patient group has an increased short-term risk for developing
Smokers who are unable or unwilling to set a fixed quit date
diabetes mellitus, which is probably due to uncontrolled weight
may accept a flexible approach. Allowing smokers to start
treatment without setting a fixed quit date and to choose the
Therapeutic drug monitoring should be performed and the dose
day to quit (between day 8 and 35) was shown to be equally
of psychopharmacological treatment adjusted if necessary (e.g.
effective This approach may make quitting more
appealing to some patients.
9.2.2.3. Stabilisation. The aim of the third phase is to maintain
10. Practical recommendations for interventions in tobacco
stable abstinence and prevent relapses. One component of relapse
dependence in mentally ill patients
prevention is how to deal with lapses and relapses .
According to the relapse model, the most constructive way for
The general interventions described below are based on the
someone to deal with a lapse is to identify the conditions and
currently available guidelines , whereby not all recom-
situations that make it more difficult to remain abstinent
mendations are fully validated for mentally ill patients.
. An important strategy in relapse prevention is firstly
The EPA recommends the following interventions for all
to change the dichotomous thinking about lapses so that they do
patients with mental illness who smoke.
not become complete relapses into earlier consumption patterns.
Lapses can represent a good opportunity to explore, understand
10.1. Record the smoking status
and learn from the mechanisms that result in a relapse. It is
important to avoid so-called relapse shock, which mainly consists
Smoking status should be evaluated and documented for every
of making a drama and catastrophe of a one-off smoking
psychiatric patient and the degree of dependence should be
occurrence, i.e. a lapse Additional important components
documented (preferentially with the FTND).
of psychotherapeutic relapse prevention include stimulus control
As described above, the FTND is widely used in treatment
(e.g. the removal of smoking tools and the avoidance of typical
studies and can supply useful information about the degree of
activities that were otherwise associated with smoking), rehear-
dependence. It also allows patients to be identified who may
sing coping strategies (practising alternative behaviour and
benefit from high-dose NRT treatment If the clinical
identifying and addressing potential difficulties) as well as the
treatment setting makes it unfeasible to use this test, at least two of
use of operand learning in the form of reward and self-
its items (namely the time when the first cigarette is smoked in the
strengthening .
morning and the number of cigarettes smoked daily) should be
Evidence-based cessation programmes include the above-
recorded because these parameters also correlate with the degree
mentioned components. Many different formal smoking cessation
of nicotine dependence . The patient should also be asked
programmes exist and include individual counselling, telephone
about previous cessation attempts and possible drug treatment
counselling and group programmes, mostly in combination with
pharmacotherapy However, there is an urgent need
for research on further treatment programmes designed specifi-
10.2. Set the time of the intervention
cally for mental health patients or psychiatric diagnosis groups.
The establishment of smoke-free hospitals and wards is also part of
Is there an acute contraindication to cessation of tobacco use or
an integrated concept of nicotine withdrawal For example, a
are there psychiatric reasons why the cessation should be
five-session, behavioral, group-oriented smoking reduction inter-
vention can significantly reduce the number of cigarettes smoked
The best time for cessation would be when the patient is in a
in hospitalized chronic clients with schizophrenia . Programs
stable phase, with no recent or planned changes in medications
for smokers with schizophrenia should focus on teaching coping
and no urgent problems take precedence . Because little is
skills for negative affect, boredom, and specific ‘‘high risk
known so far about the treatment of patients with acute mental
situations'' for smoking alongside education and pharmacological
illness, the following questions, as specified in the APA treatment
therapy. Addressing low self-efficacy for quitting, rather than
guidelines, should be considered before deciding on treatment
readiness for change alone, benefits people with schizophrenia
(p. 73–74): ‘‘Are there any psychiatric reasons for concern about
whether this is the best time for cessation? Is the patient about to
In a randomised trial, NRT combined with hypnosis signifi-
undergo a new therapy? Is the patient presently in crisis? Is there a
cantly improved long-term abstinence compared to NRT with
problem that is so pressing that time is better spent on this problem
behavioural therapy. Hypnosis combined with NRT was particu-
than on cessation of tobacco use? What is the likelihood that cessation
larly beneficial for participants with a history of depression . A
would worsen the non-nicotine-related psychiatric disorder? Are there
few small studies have supported the efficacy and feasibility of
any signs or symptoms of other undiagnosed psychiatric or substance
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
use disorders that might interfere with efforts to quit tobacco use?'' It
10.6. Perform follow-up visits
is important that the consequences of tobacco dependence are
clearly explained and that the information on the treatment
Almost all studies show that follow-up visits after quit day
process is given in detail, allowing the patient to actively
increase the quit rate; these follow-ups can also be conducted by
participate .
telephone . A patient's mental status should also be
Cessation of tobacco use is recommended in substance-
monitored. Therapeutic drug monitoring should be performed
dependent patients who are admitted to hospital for withdrawal
and the dose of psychopharmacological treatment adjusted if
from a different substance, e.g. alcohol In any case, the
necessary (e.g. clozapine) . Because psychiatric patients
diagnosis of tobacco dependence should be among the documen-
generally have a higher risk for weight gain and diabetes, weight
ted treatment goals being strived for, so that withdrawal treatment
and additional cardiovascular risk factors should be checked at
can be performed at least at a later date.
follow-up visits and respective measures taken if necessary
10.3. Give counselling
10.7. Relapse prevention and management
At least a minimum amount of counselling should be performed
The patient should be made aware that lapses and relapses are
(psychoeducation, formation of a therapeutic alliance, clinician
not catastrophes, and a new attempt with different procedures
advice, setting a quit day, additional help).
(e.g. psychotherapy, medication) should be discussed with the
As mentioned above, a procedure analogous to the so-called ‘4 A
Intervention' is recommended for the short-term intervention by
Because tobacco dependence is a chronic disorder, lapses and
physicians. Many patients do not realise that tobacco dependence
relapses are rather the rules than the exceptions on the path to
is a chronic disorder that usually requires several cessation
becoming smoke free. It is important to differentiate between a
attempts before complete abstinence is achieved . Previous
‘lapse' and ‘relapse' . Lapses are important experiences
cessation attempts should therefore be discussed in this context,
that can supply valuable information about further relapse risk and
the patient should realise that relapses are not a catastrophe and a
should be discussed with the patient.
therapeutic alliance should be formed
Physicians should bear in mind that failed quit attempts have
It is particularly important to prepare patients for what can be
been associated with an increase in depression, anxiety or suicide
expected in terms of withdrawal as patients with SMI show more
ideation and that persisting with a quit attempt while unable to
frequent and severe withdrawal symptoms after quitting smoking
achieve abstinence may be associated with mood deterioration
It is also important to explain that smoking actually
Incorporating expectancies into cognitive-behavioral treat-
increases anxiety and tension. The feeling of relaxation is
ments for smoking cessation may be useful for smokers with a
temporary and soon gives way to withdrawal symptoms and
history of depression
increased cravings, which are similar to the feelings of anxiety
. Furthermore, discussing alternative ways to cope with
11. Summary and conclusion
stressful situations and anxious feelings that may arise could
improve outcome in these patients.
Tobacco dependence is more prevalent in mentally ill patients
Clinician advice to discontinue smoking is best given in a non-
than in patients without a mental illness, as many psychiatric
judgmental, empathic and supportive manner A quit day
disorders are risk factors for tobacco dependence and tobacco
should be set or gradual reduction of tobacco consumption could
dependence is a potential risk factor for some psychiatric
be proposed as an alternative approach , especially as this
disorders. Indeed, the level of dependence seems to be more
method was recently found to have a comparable abstinence effect
severe in schizophrenia, other types of addiction or depressive
to quitting abruptly Thus, both methods can be recom-
disorder. Nevertheless, mentally ill patients also have motivation
to quit smoking, and interventions can be performed in this patient
To increase the quit rate, established programmes (individual
group. Since tobacco dependence is a dependence disorder,
therapy, group therapy, telephone coaching) should be employed
psychiatrists are the experts in performing interventions in this
wherever available
area. It is their duty to do so in view of the major impact of tobacco
dependence on, for example, the metabolism of psychotropic
10.4. Offer drug treatment with a first-line product
treatments, morbidity (such as lung cancer) and mortality.
Because of the high prevalence of tobacco dependence among
Drug treatment with a first-line product (NRT, varenicline,
mentally ill patients and the enormous individual suffering it
bupropion) should be given for even a mild degree of tobacco
causes, and also because of the high socioeconomic impact of this
dependence. Attention must hereby be paid to the severity of
disorder, it should be ensured that the therapeutic interventions
tobacco dependence and possible psychiatric side effects and
and drug treatment are paid for by the healthcare system.
interactions as well as contraindications. Patients should be
Psychiatrists and primary care physicians should be given
informed about side effects and the correct use of the drug.
training in tobacco dependence, and the treatment of tobacco
dependence should be incorporated into the catalogue of disorders
10.5. Contact within first days after quit day
to be studied during specialist training in psychiatry.
The introduction of smoking bans in psychiatric hospitals
Because the risk of relapse is highest within the first days after
results in much better protection of staff and fellow patients
stopping smoking, renewed contact (either in person or by
against the dangers of second-hand smoke. Smoking bans have
telephone) is recommended . Withdrawal symptoms
been shown to be an effective step towards quitting smoking also
and drug side effects should be discussed and the drug dose
for staff and patients on psychiatric wards and in hospitals
adjusted, if necessary. Any change in the psychopathological
Further education and training on this topic are
picture since smoking cessation should be recorded. Therapeutic
required to dispel uncertainties on the part of hospital staff and to
drug monitoring is recommended because of the altered enzymatic
increase their confidence and certainty when addressing patients
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
In addition to the education of physicians and medical
personnel, structured tobacco withdrawal programmes that are
better tailored to the special characteristics of patients with mental
illness need to be developed and implemented through future
research. In this context, the approach of harm reduction or ‘reduce
to quit' approaches should be considered.
Psychiatrists have access to the infrastructure and staff that
enable them to offer their smoking patients a way out of their
deadly tobacco dependence. However, this requires that the high
relevance of this issue and its position in everyday clinical practice
are recognised and that respective action is taken.
Disclosure of interest
This position statement was written without financial support
from pharmaceutical companies.
Dr. Ru¨ther has been a consultant for, received grant/research
support and honoraria from and been a speaker for or on the
advisory board of Astra Zeneca, Johnson & Johnson, Janssen-Cilag,
Lundbeck and Pfizer.
Pr. Dr. Bobes has received grants/research support or is a
consultant for and a member of the speakership bureaus of
Adamed, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoS-
mithKline, Janssen, Lundbeck, Pfizer, Reckitt-Benckiser, Sanofi-
Aventis, Shering-Plough, D&A Pharma, Otsuka, Roche, Shire and
Pr. Dr. Anil Batra has received research grants from McNeil,
Pfizer, Novartis, Johnson & Johnson, GlaxoSmithKline, Alkermes
and Sanofi-Aventis, and advisory board honoraria or grants for
speakership from Astra Zeneca, Merck, GlaxoSmithKline and
Pr. Dr. De Hert has been a consultant for, received grant/
research support and honoraria from and been a speaker for or on
the advisory board of Astra Zeneca, Bristol-Myers Squibb, Eli Lilly,
Janssen-Cilag, Lundbeck JA, Pfizer, Takeda and Sanofi-Aventis.
Pr. Dr. Gorwood has received grants or is a consultant for and a
member of the speakership bureaus of Astra Zeneca, Bristol-Myers
Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Servier and Wyeth.
Pr. Dr. Mann received research grants from Alkermes, Lundbeck,
McNeil, MundiPharma and Merck Sharp & Dohme. He was a
consultant to Alkermes and Desitin and is still consulting Lundbeck
and Pfizer.
Pr. Dr. Svensson has received grants/research support from
AstraZeneca, Schering-Plough, Merck Sharp and Dome, Lundbeck,
Astellas, and honoraria or consultation fees from AstraZeneca,
Janssen-Cilag, Lundbeck, Otsuka, Merck Sharp and Dome, Pfizer
and Carnegie Health Care Funds (Sweden).
Pr. Dr. Mo¨ller has received grants or is a consultant for and a
member of the speakership bureaus of Astra Zeneca, Bristol-Myers
Squibb, Eisai, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck,
Merck, Novartis, Organon, Pfizer, Sanofi-Aventis, Sepracor, Servier
We thank J. Klesing, ELS and Dr J. Keverne, for their editing
assistance, both were sponsored by research grants.
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
[263] Stapleton JA. Cost effectiveness of NHS smoking cessation services.
[239] Prochaska JJ, Hall SE, Delucchi K, Hall SM. Efficacy of initiating tobacco
dependence treatment in inpatient psychiatry: a randomized controlled
trial. Am J Public Health 2013;e1–5
[Published online ahead of print August 15].
[272] The Tobacco Atlas. 3rd ed. Geneva, Honkong: World Health Organisation; 2010.
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
Source: http://www.europsy.net/wp-content/uploads/2013/11/EPA-Guidance-on-Tobacco-Dependence-and-Strategies-for-Smoking-Cessation-in-People-with-Mental-Illness.pdf
Molecular Phylogenetics and Evolution 34 (2005) 106–117 Phylogenetic analysis of the genus Thymallus (grayling) based on mtDNA control region and ATPase 6 genes, with inferences on control region constraints and broad-scale Eurasian phylogeography E. Froufea,b, I. Knizhinc, S. Weissd,¤ a CIBIO/UP, Campus Agrário de Vairão, 4480-661, Vairão, Portugal
Original Article · Originalarbeit Forsch Komplementmed 2014;21:239–245 Published online: August 5, 2014 Evidence for the Efficacy of a Bioresonance Method in Smoking Cessation: A Pilot Study Aylin Pihtilia Michael Galleb Caglar Cuhadarogluc Zeki Kilicaslana Halim Isseverd Feyza Erkana Tulin Cagataya Ziya Gulbarana a Department of Pulmonary Diseases, Faculty of Medicine, University of Istanbul, Turkeyb Institute for Biophysical Medicine, Idar-Oberstein, Germanyc Department of Pulmonary Diseases, Faculty of Medicine, Acibadem University, Istanbul, Turkeyd Department of Community Health, Faculty of Medicine, University of Istanbul, Turkey