Clearing the air: Chronic respiratory illnesses and smoking cessation in the adult psychiatric population
Objective: To review current practice guidelines in the treatment of asthma and chronic obstructive pulmonary disease (COPD), review therapeutic options for smoking cessation, and apply current evidence to management of these conditions in the psychiatric population.
Background: Chronic respiratory illnesses and nicotine dependence are frequently encountered conditions in the psychiatric population. Psychiatric illness itself may contribute to or be affected by these conditions; medication therapy may additionally be linked to alterations in mental status. However, it is well established that when left untreated or improperly managed, chronic respiratory illness and tobacco use can negatively affect patients' quality of life and lead to increased healthcare utilization.
Methods: Current practice guidelines, literature reviews, and primary data pertaining to management of patients with asthma, COPD, and nicotine dependence were examined. Additional data regarding patients with psychiatric illness was reviewed and commented upon.
Conclusions: Management of this particular population can pose significant clinical challenges. Regardless of what factors may contribute to the disease states and their treatment, it is important for clinicians to identify and take steps to manage both respiratory and psychiatric concerns as they are able. Identification, evidence-based treatment with appropriate medication therapy, and continuing patient education should be used together to help improve patient outcomes.
INTRODUCTION
Respiratory illnesses such as asthma and chronic obstructive pulmonary disease (COPD) are frequently noted comorbidities in patients with mental illness; rates in these patients exceed the general population.12 Smoking is an additional risk factor in this population, as it is also seen in higher rates and can contribute to a number of medical conditions including respiratory disease.3–8
The relationship between and impact of both psychiatric and respiratory illnesses has been described in some available data. Asthma is reportedly diagnosed in patients with anxiety disorders approximately 33% of the time.1 Furthermore, respiratory symptoms may be reported at higher rates in individuals with anxiety and depressive disorders despite similar measurements of pulmonary function in patients with no psychiatric comorbidity.3 Nicotine dependence, anxiety, and depression have also been associated with COPD.3910 Correlations between anxiety and depression with COPD-related outcomes such as hospitalizations, increasing illness severity, and mortality have been frequently described in the literature.3910 Psychiatric illness may decrease exercise tolerance and medication adherence; these factors make treatment more challenging.3 Several studies also report a higher rate of chronic diseases, including COPD, in individuals with schizophrenia compared to those in the general population.111–13
Smoking poses another significant risk for development of respiratory illness and is also more commonly seen in patients with psychiatric comorbidities.346–8 Smoking continues to be the leading preventable cause of death as reported by the Centers for Disease Control and Prevention.5 Unfortunately, smoking rates are higher in patients with diagnosed mental illness compared to patients with no mental illness. Individuals with a history of mental illness report a lifetime smoking rate of 55.3%, compared with 39.1% of individuals without a history of mental illness. This rate increases to 59% in patients who have experienced mental illness in the previous month, with these patients accounting for approximately 44.3% of total cigarette consumption in the U.S.12
Adults with severe mental illness have higher rates of healthcare utilization and are more likely to experience potentially preventable and lengthier hospitalizations as well as increased rates of emergency medical care.13 One commonly cited reason for increased healthcare utilization is as a result of COPD exacerbations.13–14 An examination of the association between tobacco use and mortality in patients 35 years of age or older with depression, schizophrenia, or bipolar disorder found that tobacco use was implicated in 48–53% of all recorded deaths.15
The objective of this review is to provide a summary of guideline information and recommendations regarding the background and management approach to asthma, COPD, and smoking cessation. Current evidence related to the management of these conditions in the psychiatric population will also be reviewed.
ASTHMA
Definitions and pathophysiology
Asthma is a chronic inflammatory condition within the airways.16 Inflammation creates an environment of airway hyperresponsiveness, airflow limitation, and subsequent respiratory symptoms including shortness of breath, wheezing, coughing, and chest tightness.16 Airflow limitation is generally considered reversible with treatment or may resolve spontaneously; however, chronic inflammation due to many different types of cells and cellular processes can lead to airway remodeling and incomplete reversibility.1617 Patients with susceptible genetics and environmental exposures are at greatest risk for the ultimate clinical expression of asthma.1618
Diagnosis and management
The diagnosis of asthma is made by history, symptoms, and presence of intermittent symptoms of airflow obstruction that are at least partially reversible per spirometry measurement.16 The ultimate goal of therapy is to achieve asthma control as evidenced by preventing chronic and bothersome symptoms, infrequent need for rescue medication (two or fewer days per week), maintaining pulmonary function and normal activities, and preventing exacerbations.16
Pharmacotherapy should always include a rescue medication and follow a step-wise approach based on assessment of the patient to provide a maintenance regimen (Table 1).16 Long-term control medications such as inhaled corticosteroids (ICS) and potentially the addition of a long-acting beta agonist (LABA), are taken on a regular basis to achieve and maintain minimal asthma symptoms. LABAs should never be used as monotherapy in the treatment of asthma as they have been associated with an increased risk of severe asthma exacerbations and asthma-related death.161920
Additionally, rescue medications, such as short-acting beta agonists (SABA), are intended to provide rapid bronchodilation to relieve acute symptoms.16 Other maintenance medications may include: a leukotriene receptor antagonist or modifier, mast-cell stabilizer, methylxanthine, or the immune modulator, omalizumab.16 For more information regarding specific agents see Table 2. Patient education is central to appropriate self-monitoring and medication use; providers should always ensure proper inhaler technique. Minimizing triggers such as exposure to tobacco smoke and respiratory irritants can help to maximize control of symptoms and reduce exacerbations.16 Per guideline recommendations, comorbid conditions including chronic stress, depression, and others must be monitored and treated to help improve asthma management.16
Asthma and mental illness
The correlation between symptoms of panic, anxiety, and depression with asthma symptomatology has been well described in the literature, in both youth and adult populations.21–24 Patients with asthma are 1.6 times more likely to have depression and 1.5 times more likely to have anxiety than those without asthma.25 A patient who experiences panic, for example, may have an exacerbation of asthma symptoms from the body's autonomic response to stress. Conversely, the unpleasant sensations associated with symptoms of asthma may trigger fear and panic symptoms.22 Psychiatric symptoms may also occur after exposure to medications used to treat asthma. Psychiatric effects of these medications are discussed later in the article.
There is a lack of current evidence directly examining the effects of treating depression and anxiety on asthma control. The potential correlation between poor control and adherence to asthma therapy with psychiatric illness is a compelling reason to target and treat both psychiatric and respiratory symptoms.26 Psychiatric conditions including anxiety in patients with asthma may also be associated with increased emergency department visits.23 Further studies are necessary to examine the effects of antidepressants on concomitant mood and asthma symptoms. The clinician should be familiar with the relationship between these illnesses and take care to ensure both conditions are being addressed.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Definitions and pathophysiology
COPD is among the leading causes of morbidity and mortality globally, making it a vital public health concern.27 Guidelines define COPD by airflow limitation that is persistent and generally progressive in nature.28 It is associated with a chronic inflammatory response in the entire respiratory system, often related to noxious particles or gas exposure.28 COPD guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), updated in 2014, recommend an individualized patient assessment accounting for a patient's health status and risk of having a future serious health event.28
Diagnosis and assessment
Guideline recommendations include consideration of a clinical diagnosis of COPD for any patient who has dyspnea, chronic cough or sputum production, and a history of exposure to risk factors for the disease.28 Tobacco smoke, in addition to other environmental exposures, is a modifiable and important risk factor.6–828 Clinical diagnosis should always be confirmed with spirometry.28 A combined assessment that considers airflow limitation severity, exacerbation history, and symptoms per validated questionnaires should be performed in order to properly stage patients.28 Initial treatment recommendations are based on this combined classification (Table 3).
Treatment and goals
Guideline-recommended pharmacologic therapy is based on patient classification. Patients with less severe disease may only require rescue medication with a short-acting bronchodilator. As patients progress, therapy includes a long-acting bronchodilator (anticholinergic or beta agonist) with or without an ICS.28 Alternatively, for patients with more severe disease, associated with chronic bronchitis, a phosphodiesterase-4 inhibitor may be considered (Table 3).2829 The general goals of treatment for patients with COPD include relieving symptoms, improving exercise tolerance and health status, preventing disease progression, exacerbations, and reducing mortality.28
Recently Approved Agents
A number of new agents for treatment of COPD have been approved within the past few years. Aclidinium and indacaterol, a long-acting anticholinergic and LABA respectively, were approved for use as long-term maintenance treatments of bronchospasm associated with COPD.3031 Three new combination products have also been introduced: a re-formulation of the short-acting anticholinergic and SABA combination, ipratropium/ albuterol, a new combination of an ICS and a novel LABA, fluticasone/vilanterol, and the same novel LABA paired with a new long-acting anticholinergic, umeclidinium/vilanterol. The long-acting combinations are approved for long-term, once-daily, maintenance treatment of COPD.3233 Finally, roflumilast, a selective phosphodiesterase-4 inhibitor, was approved in 2011.29 For more information regarding specific agents, see Table 1.
Considerations in the psychiatric population
Although a relationship between asthma/COPD and psychiatric illnesses such as depression and anxiety has been noted, any true causal relationship is not fully understood.3435 Socioeconomic and lifestyle factors play a role in development of chronic respiratory illness, but it appears that the relationship may go beyond these risk factors.36 Recent theories describe a relationship between cytokines and inflammation found in respiratory illness with increased symptoms of psychiatric illness manifested by depressive, anxiety, and cognitive symptoms.37
Limited data is available that specifically examines management of asthma and COPD in the psychiatric population. Management of psychiatric symptoms with cognitive behavioral therapy (CBT) including methods to improve feelings of uncertainty and coping may help improve outcomes related to respiratory illness.38–40 A randomized controlled study, currently being conducted, aims to evaluate a specific disease management approach for individuals with asthma/COPD with comorbid depression and anxiety. The study is designed to compare standard care in this population with a stepwise approach that includes CBT and psychotropic medication as indicated. Endpoints to be studied include the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, and measurement scales for COPD and asthma symptoms.41 These results may add to the existing body of knowledge and elucidate the best treatment approach in this population, which is currently limited by small sample sizes and few studies with published results. Currently there are no large randomized-controlled studies specifically examining effects of pharmacologic agents for anxiety and depression on respiratory outcomes. This may be a subject of future studies.42
Several of the medications used to manage asthma and/or COPD are associated with the potential to cause or exacerbate psychiatric symptoms. For example, use of montelukast has been associated with neuropsychiatric events.43 Effects such as agitation, aggressive behavior, hostility, anxiousness, depression, hallucinations, and suicidality have been reported in post-marketing data.43 Tremor, nervousness, and tachycardia have been cited as side effects to albuterol, a SABA.44 Systemic corticosteroids have the potential to cause psychiatric adverse effects such as mania, depression, and may have variable effects on mood.45 Neuropsychiatric effects of glucocorticoids are considered to be largely dose and time-dependent, with higher doses and longer courses carrying greater risk, but can occur during courses as short as five days.46 Although guidelines only recommend short-term therapy with systemic corticosteroids, adverse psychiatric effects may still occur.2845 Effects such as euphoria and hypomania have been noted to occur with short-term therapy.45 Practitioners must consider the tolerability, risks and benefits, and closely monitor patients for signs or symptoms of adverse reactions. The aforementioned effects may potentiate symptoms of previously existing psychiatric illness. Therefore, clinicians should evaluate patients for appropriateness of therapy and/or communicate with primary care and pulmonary providers to help determine the need for continued therapy in these instances.
SMOKING CESSATION
Smoking can contribute to risk of cancer, cardiovascular disease, developmental effects, and pulmonary disease.47 Major injurious pulmonary effects of smoking are exerted through hastened decline in lung function, which over time can lead to symptomatic respiratory disease.6–848 Smoking can have an additive deleterious effect on existing asthma symptoms.4 Additionally, smoking cessation has been shown to slow the loss of pulmonary function and decrease mortality in COPD.457848 Recommending, assisting, and supporting patients during attempts to quit is one of the single most meaningful interventions a healthcare professional can make for patients with respiratory disease.
Treatment in the psychiatric population
Treatment options for smoking cessation include nicotine replacement therapy (NRT) and non-NRT, used individually or in combination (Table 4). Second line agents, nortriptyline and clonidine, lack Food and Drug Administration (FDA) approval and are generally not used clinically without other compelling indications.49 Monotherapy with NRT alone may be inadequate for controlling symptoms of withdrawal in many patients, especially in those who are heavy smokers.49 Combination therapy, particularly with bupropion and NRT, may offer the benefit of multiple mechanisms of action, improving patient ability to abstain for longer periods of time.49 The combination of transdermal NRT with bupropion sustained release (SR) is approved by the FDA and has been studied in patients with schizophrenia with some success.49 Combinations of varenicline and bupropion or varenicline and NRT are less well-studied.49–55
Psychiatric providers may express concerns regarding exacerbation of psychiatric symptoms and inherent difficulties related to smoking cessation in mental illness. Studies examining the impact of smoking cessation on patients with schizophrenia and major depression have found little support for increased psychiatric symptoms during and after smoking cessation interventions.49–55 Systematic reviews have found no significant change in the mental status of patients with schizophrenia who abstained from smoking; data regarding risk in depression is mixed with some studies reporting improvement in depressive symptoms with abstinence and one study suggesting an increase in risk of depression.5051
In a recent Cochrane review of smoking cessation, reduction, and relapse prevention trials in patients with schizophrenia, authors describe the effects of various interventions.51 Best supported is the utilization of bupropion for smoking cessation; less evidence is available for other therapies. Other therapies reviewed include NRT, varenicline, and financial incentives. Results of the review describe that NRT may not have a robust benefit in this population and that offering financial incentives to patients for smoking cessation may be beneficial in the short term, but lacks available long-term outcomes.51 Varenicline has had more published data since the Cochrane review and is discussed in further detail below. Another study of interest supporting success of smoking cessation therapy in psychiatric patients includes a 12-month open-label study of smoking cessation programming for individuals with schizophrenia. This study included adult outpatient smokers who underwent weekly group CBT sessions in addition to pharmacologic therapy with bupropion SR and transdermal nicotine patches and gum or lozenge for a total of three months.56 Continued CBT sessions were provided at less frequent intervals for a total duration of 15 months.56 Of the relatively small sample of 41 subjects, 23.5% demonstrated continued abstinence from smoking, with biochemical confirmation, by the end of the study period.56 With the exception of a single patient, significant psychiatric symptom exacerbations were not noted during the study period. The patient who reported symptom increase was successfully managed on an outpatient basis.56 In general, data are limited to patients who are considered psychiatrically stable and able to be managed on an outpatient basis during smoking cessation treatment. Acutely hospitalized patients may not have the same response to therapy and use currently lacks substantial evidence supporting efficacy in this population.
Varenicline, a nicotinic receptor partial agonist, gained approval for smoking cessation by the FDA in 2006. Since its approval, a black box warning has been added to its labeling for serious neuropsychiatric events, including agitation, hostility, depression, and behavioral changes. 52 With these possible effects, practitioners may be hesitant to prescribe this agent to patients with underlying psychiatric conditions. Studies utilizing varenicline in the psychiatric population provide evidence that supports the safety and efficacy of treatment. A 12-week study examined the effects of varenicline in smoking cessation for patients with schizophrenia. A total of 112 stable outpatients were prescribed open-label varenicline in combination with CBT. Results from this trial suggest safety and efficacy of varenicline in this population.53 Data from a double-blind, placebo-controlled relapse prevention study further support efficacy and tolerability of varenicline in patients with mental illness. Patients with diagnosed bipolar disorder, schizoaffective disorder, or schizophrenia, who remained abstinent from smoking after the 12 weeks of open-label treatment with varenicline were then randomized to receive varenicline plus a tapered CBT schedule or matched placebo and CBT for up to 52 weeks total treatment. Results found significantly higher rates of abstinence at 52 weeks compared with placebo (60% versus 19%, respectively, p<0.001) and no significant difference in psychiatric adverse events.54 Gibbons and colleagues collected and analyzed data from randomized controlled trials and observational data from a total of 8,027 subjects to examine psychiatric effects of pharmacologic interventions for smoking cessation on patients with and without mental illness.55 Psychiatric outcomes of suicidal events, depression, and agitation/aggression were not significantly different between patients with and without mental illness or between pharmacologic treatment and placebo.55 Practitioners should note that these data have limitations as they reflect treatment of psychiatrically stable patients and include observational data. Treatment of acutely ill patients with varenicline lacks sufficient data to support this approach. Clinical judgment and close monitoring should be practiced when initiating treatment.
A combination of NRT, non-NRT, and psychosocial interventions will likely provide the best opportunity for patients with mental illness to successfully quit smoking. Individual patient preferences, comorbidities, and previous quit attempts should be evaluated when designing an appropriate therapeutic plan for smoking cessation. Therapies have moderate evidence in this population, specifically in those who are psychiatrically stable. Attempts to encourage abstinence from tobacco should be made whenever appropriate.
CONCLUSION
The treatment of chronic respiratory disease and management of smoking cessation may present significant clinical challenges to the psychiatric practitioner. Literature highlights relationships between asthma/COPD and the physiological effects of respiratory illness on psychological health, as well as anxiogenic and mood altering effects of medications used to treat respiratory illness. Other factors may include the impact of mental illness itself on access to care, adherence to therapy, and ability to successfully abstain from smoking tobacco products.
Psychiatric providers should be cognizant of the association between mental illness and respiratory disease, and maintain a basic understanding of the management of these conditions. The integration of primary care and mental health services is an appealing model that may become a more common practice in the future.57 Inconsistent access to appropriate primary care and subsequent lack of identification of physical illnesses are barriers that impact patients' health and quality of life.58 Fragmentation of services, difficulties in communication of symptoms, and fear of stigma from primary care providers may limit patients' satisfaction and trust in their care.57 Close scrutiny of contributing factors to common comorbidities, appropriate treatment, continuing patient education about these disease states, and medications may help improve patient outcomes.3