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Anxiety and related disorders are the most prevalent mental disorders in the general population. There is a strong bidirectional association between anxiety and related disorders and co-occurring general medical conditions. The co-occurrence of anxiety and related disorders and general medical conditions is associated with significant impairment, morbidity and economic costs. At the same time, recognition of anxiety and related disorders in people with medical illness may be challenging when comorbid with physical illness due in part to overlap in symptomatology. Furthermore, there is a relatively limited evidence base of randomized controlled trials in this population. Additional work is needed to improve screening for anxiety and related disorders in medical illness, to enhance diagnosis and assessment, and to optimize treatment.

Anxiety disorders, obsessive-compulsive and related disorders, and trauma- and stressor-related disorders are the most prevalent psychiatric disorders in the general population [1,2], with generalized anxiety disorder the most common anxiety disorder in primary care populations [3]. Indeed, these anxiety and related disorders occur frequently with a range of general medical disorders [4,5], including gastrointestinal disease [6], pulmonary disease [7,8], cardiovascular disease [9], endocrine disorders [10], dermatological disorders [11] and cancer [12], as well as neuropsychiatric disorders such as chronic pain [13,14], migraines [15], dementia [16] and Parkinson's disease [17]. In this chapter we review the epidemiology of comorbid anxiety and related disorders and physical illness, the growing evidence of a bidirectional relationship between these sets of conditions [18] and relevant randomized controlled trials in this area.

Anxiety and related disorders are the most common psychiatric disorders worldwide, with a 12-month prevalence worldwide of between 4 and 20% [2]. The onset of anxiety and related disorders usually happens in childhood or adolescence, with many individuals first presenting with physical symptoms in primary care settings [4]. Anxiety and related disorders are prevalent throughout life [19,20,21,22]. Furthermore, while the prevalence of comorbid anxiety and related disorders in those with chronic medical illness is not as well studied as depression in medical conditions, studies which have been done indicate it is as common [22,23,24,25]. A large cross-sectional study demonstrated that generalized anxiety disorder was the most prevalent anxiety disorder in primary care settings [3].

Systematic reviews have established that anxiety disorders are particularly prevalent in gastrointestinal disorders, pulmonary disease, cardiovascular disease, endocrine disease and cancer, as well as neuropsychiatric disorders such as chronic pain and migraines. In irritable bowel syndrome, up to 95% of patients have generalized anxiety disorder or panic disorder [26]. Similarly, panic disorder and generalized anxiety disorder were more prevalent in those with peptic ulcer disease [27]. In asthma, anxiety disorders occur in at least 25% of patients [28,29]. In multiple studies of adolescents and adults with asthma, the prevalence of panic disorder and agoraphobia is almost three times that of the general population [30,31]. Another anxiety disorder that co-occurs with respiratory illness is generalized anxiety disorder [31]. Table 1 outlines medical conditions associated with anxiety symptoms and disorders.

Table 1

Common medical conditions associated with anxiety

Common medical conditions associated with anxiety
Common medical conditions associated with anxiety

The co-occurrence of anxiety and general medical conditions is associated with significant impairment, morbidity and economic costs [36,40,41,42]. For example, in a study of almost 500 medically ill persons diagnosed with anxiety disorders, those with posttraumatic stress disorder, panic disorder and social anxiety disorder were found more likely to be frequent consumers of healthcare, and to remain unable to maintain their roles and responsibilities, including work [43]. Medical comorbidities with anxiety disorders have also been shown to elevate suicide risk [44]. Adequate management of anxiety symptoms can improve outcomes of physical ill-health, and reduce the use of healthcare resources [4,45]. In addition, some work suggests that quality of life and functional ability may be improved with optimal treatment of comorbid general medical and anxiety disorders [46,47,48].

There is a growing body of evidence for a strong bidirectional association between anxiety and related disorders and co-occurring general medical conditions [14,29,49]. On the one hand, medical disorders may lead to fears about diagnosis, hospitalization, painful procedures and a foreshortened lifespan, while certain medical disorders may be linked physiologically to the development of anxiety and related disorders [50]. On the other hand, anxiety and related disorders may lead to vulnerability for various medical conditions. There may also be underlying factors that contribute to susceptibility for both anxiety disorders and physical conditions [51].

There is ongoing work to determine the precise nature of the relationships between anxiety disorders and physical illness in a number of areas. Thus, in irritable bowel syndrome, it has been suggested that infection or inflammation of the gastrointestinal tract lead to anxiety [29], while in asthma it has been postulated that increased partial pressure of carbon dioxide is responsible for panic attacks [52]. On the other hand, neurotransmitter disturbances and hypothalamic-pituitary-adrenal axis dysfunction have been postulated to play a key role in explaining how anxiety symptoms and disorders lead to medical illnesses [53].

The common underlying factors that may contribute to both anxiety disorders and comorbid physical illness have also received ongoing study. Genetic factors may, for example, predispose to both general medical conditions and anxiety disorders [54,55]. In the World Mental Health Surveys, there were strong relationships between early adversity and subsequent onset of both anxiety disorders and various physical disorders, including chronic spinal pain, chronic headache, heart disease, asthma, diabetes and hypertension [56,57].

Recognition of anxiety disorders in people with medical illness can be challenging for several reasons. Firstly, anxiety symptoms are an understandable response to the diagnosis of medical conditions. A medical condition can be sufficient enough to be a stressor for an individual to develop an adjustment disorder, and in some cases even posttraumatic stress disorder. Secondly, anxiety symptoms may overlap with symptoms of an underlying medical disorder; thus, since patients with cancer may have insomnia and fatigue, conditions such as generalized anxiety disorder are overlooked. Similarly, medications used in the treatment of physical disorders may lead to anxiety symptoms [20,49,58].

In a patient with anxiety symptoms, a range of different diagnoses can be considered. Table 2 tabulates the main features of key anxiety and related disorders. Posttraumatic stress disorder is the anxiety and related disorder that is most commonly associated with gastrointestinal, cardiac, endocrine, chronic pain, migraines and Parkinson's disease [14,22]. Symptoms of generalized anxiety disorder arguably most closely resemble those of many general medical conditions, particularly in the older population [20]. Panic disorder may, however, mimic a number of physical illnesses. Indeed, a broad range of different anxiety and related disorders have been associated with various physical illnesses.

Table 2

Anxiety and related disorders commonly seen in medically ill adult patients [14, 59]

Anxiety and related disorders commonly seen in medically ill adult patients [14, 59]
Anxiety and related disorders commonly seen in medically ill adult patients [14, 59]

Early identification of anxiety symptoms and disorders in individuals with chronic illness is important in determining better outcomes for individuals with both sets of disorders [60,61,62]. The therapeutic alliance and collaboration between medical professionals may contribute to successful management of symptoms [50]. There is, however, a paucity of robust evidence in the treatment of chronically ill patients with comorbid anxiety and related disorders [51].

Cognitive behavioral therapy has been undertaken in a number of studies of individuals with medical illness and anxiety and related disorders. A systematic review of 32 psychotherapy trials in patients with irritable bowel syndrome and anxiety disorders indicates the efficacy of cognitive behavioral therapy in reducing somatic distress [63,64,65]. A systematic review of 20 studies of cognitive-behavioral interventions in nearly 3,000 participants found that they may be effective in the management of HIV-/AIDS-associated anxiety [66]. Cognitive behavioral therapy has also been shown to reduce anxiety symptoms and distress in patients with cardiac disease and anxiety in one randomized controlled trial [67].

Behavioral strategies in anxiety disorders and comorbid medical illnesses include biofeedback, relaxation training and meditation [68,69]. Two randomized controlled trials examining the effects of biofeedback in the management of asthma [69], and another two randomized controlled trials looking at relaxation therapy showed a reduction in the use of bronchodilator agents and improved quality of life [70].

Hypnotherapy and interpersonal therapy are other treatment modalities showing promise in the management of pain related to procedures for cancer therapies [71,72], but rigorous studies are lacking in this area [14,64].

In patients with physical illness and anxiety and related disorders, there are relatively few randomized controlled trials to guide treatment choices. Thus, medications should be selected based on studies of efficacy in anxiety disorders, and on minimizing adverse events and drug-drug interactions. The selective serotonin reuptake inhibitors sertraline, citalopram and escitalopram have relatively few adverse events and are safe in interaction with other agents [73]. The serotonin-noradrenaline reuptake inhibitors venlafaxine and duloxetine have the potential advantage of being beneficial for pain symptoms, but venlafaxine has the disadvantage of requiring blood pressure monitoring [74]. Drugs such as mirtazapine and the tricyclic antidepressants may be efficacious in the treatment of some anxiety disorders, but carry a significant side-effect profile and may have worrisome drug-drug interactions [74]. Benzodiazepines and sedative-hypnotic agents may be helpful for anxiety symptoms, but should be used cautiously due to concerns of dependence [6]. The second-generation antipsychotic quetiapine is anxiolytic at low doses, and is efficacious in the treatment of some anxiety and related disorders [50], but its metabolic, cardiac and autonomic side-effect burden should be taken into consideration.

Anxiety and related disorders are frequently comorbid with chronic medical conditions. There is growing understanding of the bidirectional relationships between these sets of disorders. Recognition can be delayed due to the similarity of primary anxiety symptoms and anxiety secondary to general medical conditions. Pharmacotherapy management can be effective, but clinicians need to be aware of the side-effect burden of psychotropics in medical conditions as well as potential drug-drug interactions. There is a growing database of studies of cognitive-behavioral therapy showing efficacy in individuals with anxiety disorders and comorbid medical illness. Further work is needed to improve screening for anxiety and related disorders in medical illness, to enhance diagnosis and assessment, and to optimize treatment.

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