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James L. Levenson, MD

Primary Psychiatry. 2007;14(3):25-28

Dr. Levenson is professor in the Departments of Psychiatry, Medicine, and Surgery, chair of the Division of Consultation-Liaison Psychiatry, and vice chair for clinical affairs in the Department of Psychiatry at Virginia Commonwealth University School of Medicine in Richmond.

Disclosure: Dr. Levenson is on the depression advisory board for Eli Lilly.



Chronic pulmonary diseases are a global health problem and the number of patients being treated in primary care settings is increasing. The prevalence of a life-time diagnosis of asthma has increased in all age groups. Drug use for obstructive diseases of the airways have shown a sharp increase over the past decade. Acute exacerbations are a characteristic clinical expression of asthma and chronic obstructive pulmonary disease (COPD) and account for a significant amount of health care costs. This column reviews psychiatric issues in pulmonary disorders, including asthma, cystic fibrosis, COPD, and sarcoidosis, as well as psychopharmacology in patients with pulmonary disease. More comprehensive review of these and other lung diseases can be found elsewhere.1

Asthma

Comorbidity With Psychiatric Disorders

After hypertension, asthma is the most common chronic disease in the United States, affecting 5% to 7% of the population. Psychiatric disorders, especially anxiety disorders, are very common in patients with asthma. Both adults, children, and adolescents with asthma have a high prevalence of anxiety disorders. In children and adolescents with asthma, up to 33% may meet criteria for comorbid anxiety disorders. In adult populations with asthma, the estimated rate of panic disorder ranges from 6.5% to 24%.2 In a large population-based sample of adults, asthma was associated with a significantly increased likelihood of anxiety disorders (especially panic, generalized anxiety disorder, and phobias) and affective disorders.3 There are a number of reasons for this frequent comorbidity. Anxiety increases risk for asthma, and asthma increases risk for anxiety. Anxiety is increased by asthma attacks, chronic sensations of breathlessness, and anticipation of attacks in response to certain triggers. Respiratory distress causes a wide array of anxiety symptoms (eg, panic attacks, generalized and anticipatory anxiety, phobic avoidance), and audible wheezing aggravates social anxiety. Prospective epidemiologic studies indicate the primary risk factor for development of panic disorder in young adulthood is history of asthma as a child.4 A recent study even found a significant relationship between asthma and dental anxiety.5 An additional cause of frequent anxiety is that many drugs used to treat asthma have anxiety as a potential side effect.1

Asthma may sometimes be mistakenly diagnosed as an anxiety disorder, especially panic disorder, and some anxiety disorders (eg, panic, social anxiety) may be mislabeled as asthma. This differentiation can be difficult because shortness of breath, palpitations, sweating, chest pain, lightheadedness, fear of losing control, and even fear of dying can represent either asthma or panic anxiety. Of course, as noted above, patients can and often do have both asthma and an anxiety disorder.

Depressive symptoms are also very common in asthma. Severe asthma can be very demoralizing and lead to learned helplessness. Furthermore, higher dosage of oral or parenteral corticosteroids may cause secondary depression.

Psychological Factors in Asthma

Asthma was once regarded as a classic psychosomatic disorder, positing a central conflict revolving around unconscious dependency needs and fear of separation; however, this theory has had little empirical support. No particular personality type is more susceptible to development of asthma, but asthmatics have a tendency to hold catastrophic beliefs.6

Asthma is currently viewed as a primary respiratory disease with varying immunologic and autonomic pathophysiologic changes, but many physicians still believe that psychological factors play an important role in the precipitation and aggravation of asthma, particularly anxiety. Brittle asthmatic patients, like brittle diabetic patients, are more likely to have current or past psychiatric disorders than are other asthmatic individuals, but it is not clear whether the psychopathology is the cause or the result of more refractoy disease. Anxiety and depression are associated in asthmatic patients with more respiratory symptom complaints, but not with differences in objective measures of respiratory function.7 Asthma symptom severity increased in New York City following the terrorist attacks on September 11, 2001, and posttraumatic stress disorder was a significant predictor of the increase.8

In difficult asthmatics, there is a high prevalence of undiagnosed psychiatric morbidity, with depression being particularly prevalent. Asthma and depression have additive adverse effects on health-related quality of life. As with anxiety, depression is more strongly associated with increases in subjective measures of asthma severity than objective measures, but some investigators have found impaired pulmonary function (eg, first-second forced expiratory volume [FEV1]).9 It has been demonstrated that sadness and depression can produce respiratory effects consistent with asthma exacerbations.10 Depression is also associated with poorer adherence with asthma treatment.

In one study, psychological factors and psychosocial problems in hospitalized asthmatics were a more powerful predictor of which ones required intubation than any of the examined medical variables.11 Psychological morbidity is associated with high levels of denial and delays in seeking medical care, which may be life-threatening in severe asthma, as well as less medication adherence and consequently poorer control of asthma.12 Not surprisingly, psychopathology in severe asthmatics is associated with increased healthcare utilization, including hospitalizations as well as outpatient and emergency room visits, independent of asthma severity.13 Since psychiatric disorders are prevalent among asthmatics and are associated with worse asthma control and quality of life,14 mental health intervention deserves serious consideration as part of the regular armamentarium in asthma treatment.

Interventions with Asthma Patients

Adjuvant forms of treatment for asthma may involve psychological interventions such as biofeedback, education programs, hypnosis, stress management, symptom perception, and yoga.1 Recent small randomized, double-blind, controlled trials of progressive muscle relaxation have shown physical and psychological benefits in adolescent females15 and in pregnant women.16 There have also been several beneficial small trials of cognitive-behavioral therapy in asthma. The most systematic and up-to-date review of randomized controlled trials testing the efficacy of psychological interventions in adults with asthma found some promising results from meta-analysis but concluded that “due to heterogeneity and the low quality of included studies, this review was unable to draw firm conclusions for the role of psychological interventions in asthma.”17

Asthma in Children and Adolescents

Asthma is the most common pediatric chronic illness. More than 33% of asthmatic children have anxiety disorders.18 Comorbid psychiatric disorders may reduce adherence with treatment, impair daily functioning, and adversely affect pulmonary function. Moderate-to-severe asthma appear to be associated with a higher risk for anxiety disorders compared to mild disease. The presence of an anxiety or depressive disorder is highly associated with increased asthma symptom burden for young people with asthma.19

Posttraumatic stress symptoms are common in adolescents and their parents who have experienced a life-threatening asthma event.20 Asthma can increase family burden, and having depressed primary caretakers increases the risk of poorer treatment adherence. Despite frequent psychiatric comorbidity in asthma, rates of recognition of comorbid anxiety and depressive disorders are low in youths with asthma. Few youths with asthma and comorbid anxiety and depression receive adequate mental health treatment.21

Standard pharmacologic and psychological treatments for anxiety and depression in children are applicable to those with asthma. Family therapy may be a useful adjunct to medication to improve asthma management in children with this illness.22

Cystic Fibrosis

Cystic fibrosis affects approximately 30,000 children and adults in the US and is the most common hereditary disease in white children.18 With progress in treatment, lifespan in cystic fibrosis has significantly increased. Nearly 40% of those with cystic fibrosis are adults. Despite the severity of this disease, rates of psychiatric disorders among those with cystic fibrosis have been reported to be no greater than in the general population in children,23 adolescents,24 and adults,25 though this is probably not true in those with a severe form of the disease.26 Nevertheless, psychological factors are important in cystic fibrosis. Separation, autonomy, sexuality, and adherence are all important issues in cystic fibrosis. In adults, depression, but not FEV1, predicted whether a patient was employed.27 There are no apparent contraindications for standard treatment approaches for psychiatric disorders in those with cystic fibrosis.

Chronic Obstructive Pulmonary Disease

COPD results in progressive declines in arterial oxygen, with carbon dioxide increasing late in the course of the disease. Hypoxia causes confusion, disorientation, altered consciousness, muscle twitching, tremor, and seizures. Mild hypoxia may result in irritability, mental slowing, and impairment of memory and other cognitive functions. Prolonged hypoxia in COPD can cause permanent cognitive deficits and even dementia. Patients with hypercapnea may be lethargic and have auditory and visual hallucinations.1

Comorbidity With Psychiatric Disorders

Nicotine dependence is the most commonly associated psychiatric condition in COPD patients. Anxiety and depressive symptoms are common in patients with COPD, even when their disease is mild.28 Major depressive disorder (MDD) is very common in patients with COPD, partly due to an increased prevalence of depression in smokers. However, only a small fraction of COPD patients with MDD are treated with antidepressants. Anxiety is also common in COPD and is related to some of the same factors described for asthma including the psychological response to the experience of breathlessness as well as side effects of b-agonists. Sexual dysfunction is also common in COPD, as well as cognitive dysfunction, which is improved by supplemental oxygen.

Psychological Factors in COPD

Depression and anxiety in COPD patients have led to lower exercise tolerance, greater difficulty in stopping smoking, noncompliance with treatment, poorer health-related quality-of-life, and increased disability.1 Anxiety and depression predict a greater likelihood of relapse and rehospitalization.1,29 Depression in out-patients suffering from COPD appears to be an independent predictor of mortality.30 Chronic corticosteroid use may also exacerbate depression, emotional lability, or irritability.

Interventions with COPD Patients

Psychotherapeutic, psychopharmacologic, and rehabilitation intervention trials in COPD are reviewed in detail elsewhere.31 The first priority in the rehabilitation of patients with COPD is smoking cessation. The goals of rehabilitation treatment are to relieve symptoms, improve physical functioning, and improve patients’ coping skills.1 Patients with chronic dyspnea may avoid all activity and become home-bound and almost agoraphobic. A review of 25 published studies of psychological treatments for reduction of anxiety in patients with COPD found insufficient evidence to recommend a specific psychological treatment for anxiety in COPD,32 though relaxation techniques are useful in motivated patients.

Sarcoidosis

Sarcoidosis is characterized by noncaseating granulomas in lymph nodes, lungs, and other tissues. Onset of the illness is usually between 20 and 40 years of age. The most common symptoms are dry cough, shortness of breath, fatigue, and weight loss. The disease often follows a relapsing and remitting course, and many patients are asymptomatic. However, a minority of patients die of progressive respiratory impairment, infection, cardiac disease, or renal failure. Sarcoidosis may affect the central nervous system in approximately 5% of patients. Neurosarcoidosis can manifest as cranial or peripheral neuropathies, cognitive dysfunction, psychosis, and seizures. Most such symptoms rapidly remit with steroids. Pituitary or hypothalamic sarcoidosis may cause diabetes insipidus, the syndrome of inappropriate antidiuretic hormone secretion, hyperprolactinemia, menstrual cycle changes, or hypogonadism.1

Few studies examine psychological factors in sarcoidosis. Stress levels are high in patients with symptomatic sarcoidosis,33 and one small study found that increased life stress appeared to predict subsequent impairment of lung function.34

Psychopharmacology in Pulmonary Disease

Anxiety in pulmonary patients may be caused by breathlessness, bronchospasm, excessive secretions, or hypoxia, so the first step in treatment of anxiety is optimization of management of the patient’s respiratory illness. Many drugs used to treat pulmonary disease may cause anxiety. Theophylline can cause anxiety, nausea, tremor, and restlessness, especially at higher doses. b-adrenergic bronchodilators can cause anxiety, tachycardia, and tremor, particularly in patients who overuse their inhalers. Nonprescription asthma preparations contain nonselective sympathomimetics, which are even more likely to cause anxiety, tachycardia, and tremor, and can result in tachyphylaxis leading to very high doses, which can cause psychosis and seizures.

The respiratory depressant effects of benzodiazepines can significantly reduce the ventilatory response to hypoxia. This may precipitate respiratory failure in a patient with marginal respiratory reserve and contraindicates their use in patients with carbon dioxide retention. However, benzodiazepines are not contraindicated for use in all patients with COPD and asthma. Anxiety can often reduce respiratory efficiency, and benzodiazepines may actually improve respiratory status in some patients, especially in those with asthma or emphysema (“pink puffers”). Patients with severe bronchitis (“blue bloaters”), severe restrictive lung disease, and sleep apnea are the most vulnerable to the adverse effects of benzodiazepines. In elderly patients, shorter-acting benzodiazepines with no active metabolites, such as lorazepam and oxazepam, are preferred. While buspirone does not adversely affect pulmonary function, its limitations are its potency and delayed therapeutic effect. Antipsychotics are safer than benzodiazepines for treating acute anxiety in COPD, but rarely have caused laryngeal dystonia. Benzodiazepines should be avoided in obstructive sleep apnea. Zolpidem does not alter respiratory drive in COPD patients but may cause rebound insomnia. Selective serotonin reuptake inhibitors (SSRIs) may also be helpful in treating panic symptoms and do not have pulmonary side effects. b-blockers should not be used to treat anxiety in patients with reactive airway disease because of resulting bronchoconstriction.

When choosing an antidepressant, the side-effect profile and cytochrome P450 (CYP) interactions with pulmonary drugs should be considered. Antidepressants have little or no effect on respiratory function. Generally, SSRIs other than fluvoxamine have few drug interactions that are problematic in pulmonary patients. One exception is the antituberculosis drug rifampin. Rifampin is a CYP 3A4 substrate and may compete with many psychotropic drugs, including the antidepressants amitriptyline, imipramine, fluoxetine, sertraline, bupropion, venlafaxine, and trazodone. Rifampin may compete through the same site with anticonvulsants (eg, carbamazepine, tiagabine, and valproate) and with benzodiazepines, zolpidem, and haloperidol.

Most pulmonary medications do not affect lithium levels, but theophylline can lower lithium levels by 20% to 30%. Cholinesterase inhibitors should be prescribed cautiously in patients with asthma or COPD since acetylcholine is a potent mediator of bronchoconstriction. PP

References

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33. De Vries J, Drent M. Relationship between perceived stress and sarcoidosis in a Dutch patient population. Sarcoidosis Vasc Diffuse Lung Dis. 2004;21(1):57-63.

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