Antidepressants in the treatment of patients with COPD: possible associations between smoking cigarettes, COPD and depression
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* E J WAGENA
* M J H HUIBERS
* C P VAN SCHAYCK

The antidepressants bupropion and nortriptyline are effective agents in stimulating smoking cessation.1-4 The mechanism by which bupropion and nortriptyline act as smoking cessation aids is unknown, as is its exact mechanism of antidepressant activity. What we do know is that the effects on smoking cessation are not produced through the treatment of depression itself.1-4 Bupropion and nortriptyline are thought to produce their therapeutic antidepressant effects via inhibition of the neuronal uptake of noradrenaline and/or dopamine. Furthermore, the effects of nicotine are supposed to occur through the stimulation of dopaminergic pathways. Because (1) smoking cigarettes is the major risk factor for chronic obstructive pulmonary disease (COPD), (2) smoking cessation is the main preventive measure in reducing the decline in lung function in patients at all stages of COPD, and (3) patients with COPD can be characterised as a population of chronically ill patients with a higher than normal prevalence of psychiatric disorders, the use of antidepressants in the treatment of these patients needs further attention.

Smoking cigarettes is the main cause of COPD in 80–90% of cases (fig1, arrow 1). It is the single most important way of affecting outcome in patients at all stages of COPD,5 and is the only evidence based treatment (as confirmed in the Lung Health Study6) which has been proved to slow down the development of the disease by preventing further deterioration in lung function. It is the only intervention at this time to affect long term decline in forced expiratory volume in one second (FEV1). However, for most people stopping smoking is difficult, especially when the attempt to stop is being hampered by the co-existence of a psychiatric disorder. The effectiveness of smoking cessation programmes can be influenced by the co-existence of depression or other psychiatric disorders. Both depression and depressive symptoms are independently associated with failure to quit smoking and relapse.

![Figure 1](http://thorax.bmj.com/https://thorax.bmj.com/content/thoraxjnl/56/8/587.2/F1.medium.gif)

[Figure 1](http://thorax.bmj.com/content/56/8/587.2/F1)

Figure 1 
Association between smoking cigarettes, COPD, and depression.

Patients with COPD have repeatedly been characterised as a population of chronically ill patients with a higher than normal prevalence of psychiatric disorders such as depression.7 ,8 Psychiatric disorders complicating COPD may be overlooked.9 Many clinicians remain uncertain about the exact status of depressive moods and associated symptoms in patients with chronic diseases.10 The physical illness itself is often considered reason enough for patients to be depressed.9This could lead to an underestimation of the prevalence of psychiatric disorders in the physically ill because symptoms of a psychiatric disorder such as severe fatigue or insomnia may be attributed to physical illness when they are, in fact, caused by psychological illness, and these increased scores may be related to an understandable and expected emotional reaction to the physical illness itself.7 ,10 However, distinguishing depression from COPD can be difficult because several of the same emotional and physical signs and symptoms are associated with both disorders.9 ,11 ,12 Until now it has not been clear whether depression is more prevalent in patients with COPD than in those without COPD or those with other chronic illnesses. We hypothesise that COPD, as a chronic disease, causes patients to suffer from depressive symptoms which may lead to the development of depression (fig 1, arrow 2).

Furthermore, although a positive association between psychiatric disorders and cigarette smoking has been well established,5 ,6 the association between smoking cigarettes, COPD, and depression is not yet clear. Several explanations for the association between psychiatric disorders and cigarette smoking have been proposed. According to the notion of self-medication, smokers use nicotine to medicate their depressed mood.13Alternative explanations include a causal influence of smoking on major depression based on the possible effects of long term nicotine exposure on neurobiological systems implicated in the aetiology of depression,14 and the effects of shared environmental or genetic factors that predispose to both smoking and major depression.14 The observed influences from depression to subsequent daily smoking (fig 1, arrow 3a) and smoking to depression (fig 1, arrow 3b) support the plausibility of shared aetiologies (or at least their close interrelationship).13 However, separate causal mechanisms in each direction might also operate, including self-medication of depressed mood as a factor in smoking progression and neuropharmacological effects of nicotine on neurotransmitter systems linked to depression.13 The association between smoking cigarettes and depression is certainly present but is not yet understood.

In daily practice it is quite common to treat the symptoms of COPD as separate disease entities. However, for continuity of the effect of individual treatments in patients with COPD, we recommend a holistic approach in which the possible co-existence of multiple problems is being integrated. For example, the attempt to quit smoking and maintain abstinence from smoking might be hampered by the co-existence of depression. The use of antidepressants such as bupropion or nortriptyline is therefore of particular interest in the treatment of patients with COPD.

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