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
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 22.214.171.124. 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) 126.96.36.199. 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.
188.8.131.52. 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  Stapleton JA. Cost effectiveness of NHS smoking cessation services.  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].
 The Tobacco Atlas. 3rd ed. Geneva, Honkong: World Health Organisation; 2010.
T. Ru¨ther et al. / European Psychiatry 29 (2014) 65–82
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