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Abstract

Objective: To present an overview of the relationship between depression and cigarette smoking and to provide recommendations for clinicians who wish to help patients with a history of depression to stop smoking.

Method: English language journal articles published in the last 15 years on clinical material related to depression history, smoking cessation and related health issues were collected via MEDLINE, PsycINFO and Cochrane Library database searches.

Results: Nicotine dependence is associated with increased rates of depression prior to and after taking up smoking as well as increased rates of suicidal ideation. Depression history is associated with increased rates of nicotine dependence, problems with smoking cessation and depression after cessation. While nicotine replacement and counselling are effective for smoking cessation, standard smoking cessation strategies may not pay sufficient attention to the needs of smokers with a depression history. Some antidepressants (bupropion and nortriptyline) are particularly effective for those with a lifetime depression history as they appear to assist with dysphoria during withdrawal and prevent relapse. Psychological and lifestyle strategies, such as motivational interviewing, relaxation exercises and mood charts, assist in mood regulation over and above the standard smoking cessation treatments for smokers with a depression history, who require more attention to relapse of depression and smoking after quitting.

Conclusions: There is a complex and circular relationship between depression, smoking and medical illness that complicates smoking cessation in those who have a history of depression. Depression-history smokers require a multimodal approach to assist with mood regulation and nicotine withdrawal. Further research is required to identify effective strategies to reduce smoking in this context.

Keywords

depression major depression nicotine dependence smoking cessation tobacco

It is now well recognized that the cigarette is an efficient delivery system for nicotine, and that nicotine is highly addictive, with a number of psychoactive effects [1], [2]. A recent review [2] notes that many factors are thought to contribute to the addictive potential of nicotine. These include the early onset of drug use with subsequent neuroadaptation, rapid onset of action, capability to produce subtle relaxation or stimulation, ability for self-titration, short and frequent dosing interval, oral gratification, appetite suppression and weight loss. Due to the legal status of cigarettes, there are also multiple everyday cues for smokers. These include the promotion of effects on self-image and, until recently, widespread community acceptance. Nicotine has many physiological effects, including increases to heart rate and blood pressure and restriction of blood flow to cardiac muscle. It promotes the release of a cascade of neurotransmitters, including epinephrine and endorphin, leading to increased alertness and a short-term sense of wellbeing [1].

Tobacco dependence has many of the features of a chronic disease and clinicians are becoming increasingly aware that the majority of smokers cycle through periods of relapse and remission over many years [3]. There are well-recognized guidelines for smoking cessation [3–6] which are successful for many smokers. The majority of Australians are now non-smokers with smoking rates around 25% for men and 21% for women [7]. Those who continue to smoke despite its widely publicised adverse effects are likely to be heavy nicotine-dependent smokers with a history of unsuccessful quit attempts [2], [8]. In the UK, these ‘hard core smokers’ [9] comprise about 16% of all smokers and, as well as having higher rates of nicotine dependence, also have higher rates of socioeconomic deprivation, increasing age and a denial that smoking has affected their health, or will affect it in the future. This nicotine-dependent group is also more likely to have smoking-related health problems such as cardiovascular disease, cerebrovascular disease and emphysema, increasing both the risk of depression and the complexity of their medical and psychiatric management [2], [3].

These ‘treatment-resistant’ smokers are often made to feel that they are ‘not trying hard enough’ to quit, but many doctors are unaware of the difficulties they experience. The history of depression in these ‘hard core smokers’ is of particular salience for psychiatrists and is becoming increasingly prominent as other smokers successfully quit. This paper considers issues relating to the management for those nicotine-dependent smokers who have a lifetime depression history (DHS) and who wish to cease smoking. Previous reviews have examined depression and smoking-related factors, generally in the American literature [3],[10–12]. The present review is unique in that it integrates a series of issues, demonstrating their complex interrelationships. It is intended to provide a clinically-orientated overview of the relevant research, with recommendations for the Australasian context that take recent clinical advances into account.

Interactions between tobacco smoking and depression

The first report of the influence of depression on smoking cessation was not until the late 1980s [13]. Since then, a number of large cross-sectional and followup studies have reported that people with a history of depression are more likely to smoke [14], to smoke more heavily, and to be more nicotine dependent [15–17], than those without such a history. The relationship between depression and smoking is strongest in those with heavy smoking and nicotine dependence [18]. Smokers are more likely to start, restart or increase their smoking during periods of distress [19], and those with recurrent episodes of depression have the highest rates of smoking [20], [21]. Depression reported in adolescence appears to predict heavy smoking in adulthood [14], and the early onset of smoking is a strong predictor of a range of highrisk adolescent behaviours [22]. The National Survey of Mental Health and Wellbeing reported rates for current major depression of 3.2% [23]. A wide range of social and lifestyle factors were examined for association with current major depression, with the strongest correlates being unemployment, smoking, and having a medical condition, followed by being in mid-life, previously married and female. Groups considered at risk for taking up smoking when depressed or at risk of more severe withdrawal problems when quitting are outlined in Table 1.

Table 1.

Groups considered at risk for problems related to smoking and depression

Likewise, higher rates of depression among smokers have been observed. In the Australian national study [23], current smokers had nearly twice the risk of an episode of major depression in the past month compared to non-smokers (OR = 1.78, 95% CI = 1.18 − 2.68), with previous smokers having an intermediate rate (OR = 1.52, 95% CI = 1.05 − 2.20). Smokers report more depressive symptoms than non-smokers [24], have more frequent and more severe episodes of depression [20], are more likely to experience suicidal ideation when depressed [20],[25–27] and have higher rates of suicide [26], [27] (see Table 2). Some studies suggest that the association between smoking and suicide may be dose-related: the heavier the smoking, the greater the risk of suicide and depression [25], [28]. There are also links between smoking and neuroticism, which is a risk factor for depression for both sexes [29]. Smokers of both sexes with high neuroticism scores are more vulnerable to repeated episodes of depression and have higher rates of smoking with higher smoking relapse rates. High neuroticism has also been proposed to mediate the association between panic disorder and smoking [30].

Table 2.

Recent studies reporting rates of depression-related problems for current nicotine-dependent smokers compared to non-smokers

Research at the neurophysiological level indicates that smoking has complex effects. Smoking causes pleasure directly and immediately through the release of postsynaptic neurotransmitters [1]. This is most apparent after a break from smoking, such as the first cigarette of the morning. Dependent smokers tend not to gain so much ‘pleasure’ from subsequent cigarettes, which simply alleviate the withdrawal symptoms that start 20–30 minutes after the last cigarette [1]. In the longer term, sustained nicotine use leads to down-regulation of the dopamine and serotonin receptors due to excessive stimulation of post-synaptic receptors [2]. Other as yet unidentified compounds in tobacco smoke decrease monoamine oxidase activity and lower platelet MAO-B and MAO-A activity, with the potential to display some antidepressant effects [31].

The finding that post-mortem brains of long-term smokers have significantly fewer α-2 adrenoceptors and significantly less tyrosine hydroxylase (involved in brain noradrenaline and dopamine synthesis) has promoted speculation that nicotine acts in a similar fashion to antidepressant drugs [32]. The association between smoking and suicidal behaviour is thought to be due to lower concentrations of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampal region, lower 5-HIAA in the median raphe and higher serotonin receptor density [1].

In summary, several hypotheses concerning the direction of association between smoking and depression have been proposed. Compelling evidence for the selfmedication hypothesis (that depressed people smoke as a means of reducing dysphoria) [33] has been found from a 40-year follow-up study. People who are vulnerable to depression are likely to take more risks in general, including smoking, and make less use of health care services [34], [35]. Other proposals include common genetic vulnerability factors predisposing to both smoking and depression [18], [36], [37], or smoking acting as an antecedent factor associated with the development of depression [32], as suggested by studies reporting a dose-relationship between smoking and suicide and depression [25], [28]. The underlying mechanisms are still not entirely clear [37], and there may be more than one mechanism operating via nicotine and the myriad of other components of cigarette smoke [31].

Other physical health-related interactions related to tobacco smoking and depression add to the complexity. For example, patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of major depression, with depression onset acting as a precipitant of relapse of COPD [38]. A similar relationship exists between cardiovascular disease and depression, where depression appears to lead to increased cardiac events and poorer prognosis [39]. Smoking is also a risk factor for vascular disease and indirectly to later onset ‘vascular depression’ [40], [41]. Further, comorbidity exists between nicotine dependence and other substance dependence including alcohol, and some psychiatric disorders including mixed and generalized anxiety disorders, with the severity of nicotine dependence found to be directly correlated with the number of comorbid disorders [42].

Overall, regular smokers with a history of depression (DHS) have higher rates of nicotine use, dependence and poorer abstinence, than regular smokers without a depression history [21], [43]. The most important elements of ‘depression history’ that predict depressive symptoms during quitting and risk of relapse include early onset of first depressive episode, baseline depressive symptoms and history of recurrent depression [44]. There seems to be a complex and circular relationship between depression, smoking and medical illness, with factors related both to inhalation of cigarette smoke and the effects of nicotine. Thus, smoking cessation ‘has numerous benefits, including improved metabolic efficiency and stress test performance, increased tissue perfusion, reduced cortisol, reduced immunosuppression and possibly, reduced self-perceived stress and injury death rates’ [45].

Management of dependent smokers with a depression history

There are a number of clinical management strategies for those willing to quit smoking [3], [4], [6], [46], including material from Australia [5] and New Zealand [47]. Recent US guidelines [3] were based on 50 meta-analyses of 6000 articles published in peer-reviewed journals from 1975 to 1999, using placebo/comparison evaluated assessment or treatment for randomised patients and follow-up of at least 5 months from quit date. The Australian, US and New Zealand guidelines for best clinical practice all include some information for smokers with a history of depression. These guidelines recommend the use of pharmacological aids in conjunction with behavioural therapy for all smokers trying to quit smoking [3], [46], with a multimodal approach being particularly important for those with a depression history. It is recommended that psychiatrists inform patients with a depression history about the problems with commencing or resuming smoking. Follow-up is essential for the DHS group, in which relapse prevention for both smoking and depression needs to be monitored.

A recent review considered the effectiveness of antidepressant medications (bupropion, doxepin, fluoxetine, imipramine, moclobemide, nortriptyline, selegiline, sertraline, tryptophan and venlafaxine) and anxiolytics (diazepam, meprobamate, metoprolol, oxprenolol and buspirone) in aiding long-term smoking cessation [10]. There are now studies linking both buproprion and nortriptyline to increased rates of cessation, although no evidence has been found for anxiolytics. The authors of a randomised controlled study [48] confirmed their earlier reports about the effectiveness of nortriptyline when they found that both nortriptyline and bupropion were efficacious in producing abstinence in cigarette smokers. They stated in an earlier study [49] that ‘(buproprion and nortriptyline) have similar effects on smoking cessation: both have effects on noradrenergic transmission, although effects on other neurotransmitter systems may differ between the two drugs. Independent of diagnosis, nortriptyline seems to have alleviated the increases in poor mood that occurred in the first few days after smoking cessation’. The later RCT [48] was the first to account for the problem in DHS of developing an onset of depression after ceasing antidepressants given for smoking cessation, by providing the option of continuing antidepressants after the conclusion of the study. The additional antidepressant properties are doubly useful for those with a previous depression history, in which an antidepressant coupled with higher dosage of nicotine replacement is often required [50]. Another recent review of bupropion [51] stated that there appear to be no significant differences in outcomes between bupropion and nortriptyline for smoking cessation. Doxepin has also been shown, in an open study, to assist with cessation-associated insomnia and withdrawal symptoms [52]. Other antidepressants, including the selective serotonin reuptake inhibitors (SSRIs), assist smokers who are depressed prior to nicotine withdrawal with maintenance of mood, but do not appear to have specific anticraving properties [50], [53], [54].

As stated earlier, dependent smokers with a depression history are more likely to have a number of health problems (including respiratory, cardiovascular and other vascular diseases) that impact on the choice of antidepressant (see Table 2). One study [38] examined the effect of nicotine-replacement therapy and counselling versus an antidepressant (bupropion or nortriptyline) with counselling, to combat the physiological as well as the psychological aspects of smoking cessation in patients with chronic obstructive airways disease, a group who have a higher than expected rate of depression [38]. They found that compared to the placebo, both bupropion and nortriptyline (with counselling) were ‘particularly effective smoking cessation aids in this patient group’, with relative risk for nortriptyline at 2.7 (95% CI = 1.3 − 5.3) and for bupropion at 1.5 (95% CI = 1.1 − 2.6).

In Australia, bupropion was widely introduced as a smoking cessation aid in late 2000 [55]. It was first used as an antidepressant, and along with nortriptyline, was later found to have specific properties affecting dopamine-mediated addiction mechanisms [3], [10], [21]. A recent review of the role of bupropion for smoking cessation found that bupropion doubled abstinence rates at 6 and 12 months compared to placebo [51]. Approximately 35% of smokers who received bupropion in addition to NRT were non-smokers after 12 months, compared to 16% of smokers who received NRT alone [56]. Bupropion and nortriptyline do appear to be helpful in those who fail on nicotine replacement therapy alone [10], which is often the case in those with comorbid depression and medical problems. There has been a resurgence of interest in nortriptyline, which has gained a specific indication as a second line agent for smoking cessation in New Zealand [47] and the US [3].

Given the relationship between smoking cessation and depressed mood in smokers with a history of depression, a number of psychological and lifestyle strategies have been combined with standard cessation treatments in order to increase success. While one study found that the addition of five group sessions of mood management intervention to an antidepressant drug treatment did not appear to improve smoking cessation outcome [48], this was contrary to earlier findings by the same author [49], [57]. These studies found that cognitive behavioural mood management combined with standard smoking cessation techniques significantly increased smoking abstinence among those with a history of major depression, but not for smokers without past major depression. Nevertheless, in the later study which found contrasting results [48], the psychosocial intervention did produce better abstinence rates than medical management alone, and the potentially small numbers of past history depression subjects allocated to each of six treatment conditions may have limited the statistical power for detection of treatment effects among this subpopulation.

Brown et al. [58] investigated the effect of cognitivebehavioural therapy for depression (CBT-D) on smoking cessation outcome in a sample of smokers with a history of major depression. CBT-D combined with standard smoking cessation treatment led to better outcomes than standard smoking cessation treatment alone (with equal session times) for heavier smokers and for smokers with recurrent, but not single, episodes of major depression. The authors proposed that CBT-D provides specific benefits for some, but not all, smokers with a history of depression. The group of particular benefit appear to be the ‘hard-core’ smoking group, which may explain the disparate results mentioned above.

Another concern for psychiatrists is the marked cooccurrence of psychotic disorders and other mental disorders with smoking. When compared to the general population, those with schizophrenia and bipolar disorder have been found to smoke at higher rates (around 80% of sufferers) and with greater daily consumption [43]. Smoking is known to enhance the metabolism of some antipsychotics (including olanzapine and clozapine), but not others (e.g. rispiridone). Smoking is also known to decrease rates of parkinsonian side-effects, but to increase rates of akathisia and tardive dyskinisia [59]. In addition, bupropion can potentiate psychosis and lower seizure threshold [60], [61]. SANE Australia has collaborated with the Australian and New Zealand College of Psychiatry to produce guidelines for smoking cessation in this group [62].

The concurrent use of cannabis is becoming increasingly relevant to smoking cessation treatment strategies. The number of cannabis smokers, particularly in young people, is increasing [63], [64], and in some countries cannabis smoking is becoming more common than tobacco smoking [65]. In terms of health risk, cannabis use is linked to depression [66–69] and suicidal ideation [67], with similar health effects to smoking tobacco, but appearing at a younger age [70]. Cannabis smoking may increase the difficulty of tobacco cessation [71], [72] although the impact of cannabis on tobacco use is still not entirely clear [73–76]. Some evidence exists for the worsening of mood of those administered bupropion during marijuana abstinence, with reports of higher irritability, restlessness, depression and lack of motivation compared to the placebo group [77]. The routine assessment of cannabis use is an important part of the evaluation of DHS and smoking cessation.

Discussion

The description of the relationship between smoking and depression as ‘complex, pernicious, and potentially life-long’ [54] is alarming, but serves to convey the difficulties in dealing with an important clinical issue. There are still many unanswered questions. A review of the literature [11] concluded that lifetime history of depression was not an independent factor in its own right. Rather, the difficulties with smoking cessation were likely to be due to ‘an enduring trait vulnerability, reflected by a history of recurrent depression and a vulnerable state, reflected by elevated depressive symptomatology prior to treatment’. The same review concluded that there is little information about the management of people who are currently depressed (as they are excluded from most studies), and a paucity of information that discriminates ‘lifetime history’ in terms of types and frequency of depressive episodes.

It is advisable to identify people who have a history of depression (especially repeated episodes) and longstanding personality traits likely to lead to depression, and to be able to inform them about the issues discussed in this paper. An early onset of nicotine dependence may point to issues related to family history of depression or dependence syndromes and childhood abuse [78], [79], psychological factors such as poor self-esteem and social skills and the presence of anxiety disorders [80], [81]. Psychiatrists have been found to offer smoking cessation counselling to certain high-risk subgroups, such as those over 50 with medical diagnoses, and tend to only counsel in their first visit [82]. They may be missing important opportunities to offer counselling to other high-risk groups (see Table 3), and on follow-up patient visits [82].

Table 3.

Smoking cessation strategies for smokers with a depression history

We are assuming that psychiatrists are familiar with the current evidence-based treatment guidelines for depression [83] and these guidelines have not been discussed. There are also smoking cessation guidelines [5], [84], with Level 1 evidence (based on National Health and Medical Research Council grading) for smoking cessation strategies including NRT, bupropion and nortriptyline for the general population. Psychiatrists are not necessarily familiar with smoking cessation guidelines, although the importance of issues related to the general health of patients with serious mental health problems is bringing this issue into focus. There are no clear evidence-based guidelines for smokers with a depression history as the research is still being undertaken, but this paper presents material that can provide a background to the clinical management of nicotine dependence and depression, which often occur with other physical and mental health problems.

A commonly voiced concern is whether it is appropriate to expect depressed patients to stop smoking. In this respect, regular smoking seems to worsen suicidal ideation and lead to new onsets of depression, but does not appear to worsen current depression. Given the complexity of the clinical situation, it is not advisable to stop smoking precipitously, but rather to have a planned approach with education and collaborative treatment that may involve the gradual implementation of an antidepressant prior to the quit date. In Table 2, we have summarized some management strategies that may be useful in addition to the principles in the clinical practice guidelines. Motivational interviewing [85] is extremely helpful in assisting clinicians to explore likely barriers and is a useful part of a psychiatrist's skill set.

Currently in Australia, bupropion has a time-limited indication for smoking cessation but no indication as an antidepressant. For those with a depression history, an antidepressant may be required for a longer course than indicated for smoking cessation. While nortriptyline is generally used as a second-line treatment [3], [47], it appears to have very similar properties and effectiveness to bupropion in smoking cessation [10]. There are situations where it may be worth prescribing nortriptyline to those with a depression history, such as when the patient requires ongoing antidepressant medication after the smoking cessation period, has already failed with bupropion or has contraindications to it, or where there are financial considerations.

Following successful smoking cessation, relapse prevention of both depression and smoking can be tackled simultaneously. This involves encouragement of activities promoting mood stability and maximizing health, and also identifying situations (psychological, interpersonal and medical) that have previously been associated with relapse [49], [86]. It appears that structured psychological approaches add benefits, particularly for heavily dependent smokers and those with repeated episodes of depression, over and above those of antidepressants and NRT [11], [48]. These have also been shown to enhance motivation and decrease vulnerability to depression [11]. Approaches include problem solving, coping skills and social support training, substitution therapy [85], [87] (see Table 3), stress management strategies such as physical activity and meditation [88], as well as other cognitive behavioural strategies.

Issues surrounding depression-history smokers are likely to grow in importance in terms of clinical and medicolegal issues, particularly with the advent of restrictions such as smoke-free environments. These smokers face numerous barriers to smoking cessation. A multimodal approach is recommended to increase effectiveness, which combines an antidepressant, NRT and psychological interventions to provide mood stability and prevent depression relapse. Successful smoking cessation is likely to reduce episodes of major depression, panic and suicidal ideation, and improve general fitness (including increased cardiovascular fitness) and lifestyle opportunities.

Footnotes

Acknowledgements

The NSW Institute of Psychiatry provided support for Karen Arnold; Heather Niven is supported by the NHMRC Program Grant 222708 and the Black Dog Institute also receives support from a NSW Centre for Mental Health Infrastructure Grant. Thanks to Andrea Millar for secretarial assistance.

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Grey Lungs and Blue Moods: Smoking Cessation in the Context of Lifetime Depression History

Abstract

Keywords

Interactions between tobacco smoking and depression

Management of dependent smokers with a depression history

Discussion

Footnotes

Acknowledgements

References