Skip to Main Content
Skip Nav Destination
Open Access License / Drug Dosage / Disclaimer
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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.

1.
Kessler RC, Aguilar-Gaxiola S, Alonso J, et al: The global burden of mental disorders: an update from the WHO World Mental Health (WMH) Surveys. Epidemiol Psichiatr Soc 2009;18:23-33.
2.
Kessler RC, Berglund P, Demler O, et al: Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593-602.
3.
Fava GA, Porcelli P, Rafanelli C, et al: The spectrum of anxiety disorder in the medically ill. J Clin Psychiatry 2010;71:910-914.
4.
Mago R, Gomez JP, Gupta N, et al: Anxiety in medically ill patients. Curr Psychiatry Rep 2006;8:228-233.
5.
Skodol AE: Anxiety in the medically ill: nosology and principles of differential diagnosis. Semin Clin Neuropsychiatry 1999;4:64-71.
6.
Lydiard RB: Irritable bowel syndrome, anxiety and depression: what are the links? J Clin Psychiatry 2001;62:38-45.
7.
Brenes GA: Anxiety and chronic obstructive pulmonary disease: prevalence, impact, and treatment. Psychosom Med 2003;65:963-970.
8.
Cruz I, Marciel KK, Quittner AL, et al: Anxiety and depression in cystic fibrosis. Semin Respir Crit Care Med 2009;30:569-578.
9.
Fan AZ, Strine TW, Jiles R, et al: Depression and anxiety associated with cardiovascular disease among persons aged 45 years and older in 38 states of the United States, 2006. Prev Med 2008;46:445-450.
10.
Simon NM, Blacker D, Korbly NB, et al: Hypothyroidism and hyperthyroidism in anxiety disorders revisited: new data and literature review. J Affect Disord 2002;69:209-217.
11.
Hayes J, Koo J: Psoriasis: depression, anxiety, smoking, and drinking habits. Dermatol Ther 2010;23:174-180.
12.
Mitchell AJ, Chan M, Bhatti H, et al: Prevalence of depression, anxiety, and adjustment disorder in oncological, haematological, and palliative-care settings: a meta-analysis of 94 interview-based studies. Lancet Oncol 2011;12:160-174.
13.
Williams LJ, Pasco JA, Jacka FN, et al: Pain and the relationship with mood and anxiety disorders and psychological symptoms. J Psychosom Res 2012;72:452-456.
14.
Jordan KD, Okifuji A: Anxiety disorders: differential diagnosis and their relationship to chronic pain. J Pain Palliat Care Psychother 2011;25:231-245.
15.
Culpepper L: Generalized anxiety disorder and medical illness. J Clin Psychiatry 2009;70:20-24.
16.
Wragg RE, Jeste DV: Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989;146:577-587.
17.
Stein MB, Heuser IJ, Juncos JL, et al: Anxiety disorders in patients with Parkinson's disease. Am J Psychiatry 1990;147:217-220.
18.
Sanna L, Stuart AL, Pasco JA, et al: Physical comorbidities in men with mood and anxiety disorders: a population-based study. BMC Med 2013;11:110.
19.
Hirsch JK, Walker KL, Chang EC, et al: Illness burden and symptoms of anxiety in older adults: optimism and pessimism as moderators. Int Psychogeriatr 2012;24:1614-1621.
20.
Wetherell JL, Ayers CR, Nuovo R, et al: Medical conditions and depressive, anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder. Aging Ment Health 2010;14:764-768.
21.
Pao M, Bosk A: Anxiety in medically ill children/adolescents. Depress Anxiety 2011;28:40-49.
22.
Scott KM, Bruffaerts R, Tsang A, et al: Depression-anxiety relationships with chronic physical conditions: results from the World Mental Health Surveys. J Affect Disord 2007;103:113-120.
23.
Chou SP, Huang B, Goldstein R, et al: Temporal associations between physical illness and mental disorders - results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Compr Psychiatry 2013;54:627-638.
24.
Scott KM, McGee MA, Wells JE, et al: Obesity and mental disorders in the adult general population. J Psychosom Res 2008;64:97-105.
25.
Beitman BD, Kushner MG, Basha I: Follow-up status of patients with angiographically normal coronary arteries and panic disorder. JAMA 1991;265:1545-1549.
26.
Whitehead WE, Palsson O, Jones KR: Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology 2002;122:1140-1156.
27.
Harter MC, Conway KP, Merikangas KR: Associations between anxiety disorders and physical illness. Eur Arch Psychiatry Clin Neurosci 2003;253:313-320.
28.
Katon WJ: Panic Disorder in the Medical Setting. Publication No. 94-3482. Washington, National Institutes of Health, 1994.
29.
Katon W, Lin EH, Kroenke K: The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen Hosp Psychiatry 2007;29:147-155.
30.
Goodwin RD, Jacobi F, Thefeld W, et al: Mental disorders and asthma in the community. Arch Gen Psychiatry 2003;60:1125-1130.
31.
Smoller JW, Simon NM, Pollack MH, et al: Anxiety in patients with pulmonary disease: comorbidities and treatment. Semin Clin Neuropsychiatry 1999;4:84-97.
32.
Lin EH, Korff MV, Alonso J, et al: Mental disorders among persons with diabetes - results from the World Mental Health Surveys. J Psychosom Res 2008;65:571-580.
33.
Smith DF, Gerdes LU, et al: Meta-analysis on anxiety and depression in adult celiac disease. Acta Psychiatr Scand 2012;125:189-193.
34.
Arnold LM: Antidepressants for fibromyalgia: latest word on the link to depression and anxiety. Curr Psychiatry 2002;1:49-54.
35.
Smedstad LM, Vaglum P, Kvien TK, et al: The relationship between self-reported pain and sociodemographic variables, anxiety and depressive symptoms in rheumatoid arthritis. J Rheumatol 1995;22:514-520.
36.
Zaubler T, Katon W: Panic disorder in the general medical setting. J Psychosom Res 1998;44:25-42.
37.
Yanovski SZ, Nelson JE, Dubbert BK, et al: Association of binge eating disorder and psychiatric co-morbidity in obese subjects. Am J Psychiatry 1993;150:1472-1479.
38.
Vieweg WV, Julius DA, Benesek J, et al: Posttraumatic stress disorder and body mass index in military veterans. Preliminary findings. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1150-1154.
39.
Van den Heuvel L, Chisinga N, Kinyanda E: Frequency and correlates of anxiety and mood disorders among TB- and HIV-infected Zambians. AIDS Care 2013;25:1527-1535.
40.
Cully JA, Graham DP, Stanley MA, et al: Quality of life in patients with chronic obstructive pulmonary disease and comorbid anxiety and depression. Psychosomatics 2006;47:312-319.
41.
Brenes GA: Anxiety, depression and quality of life in primary care patients. Prim Care Companion J Clin Psychiatry 2007;9:437-443.
42.
Sareen J, Jacobi F, Cox BJ, et al: Disability and poor quality of life associated with comorbid anxiety disorder and physical conditions. Arch Intern Med 2006;166:2109-2116.
43.
Stein MB, Roy-Byrne PP, Craske MG, et al: Functional impact and health utility of anxiety disorders in primary care outpatients. Med Care 2005;43:1164-1170.
44.
Torres AR, Ramos-Cerqueira AT, Ferrao YA, et al: Suicidality in obsessive-compulsive disorder: prevalence and relation to symptom dimensions and comorbid conditions. J Clin Psychiatry 2011;72:17-26.
45.
Roy-Byrne PP, Davidson KW, Kessler RC, et al: Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry 2008;30:208-225.
46.
Hofmeijer-Sevink MK, Batelaan NM, van Megen HJ, et al: Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands study of depression and anxiety (NESDA). J Affec Disord 2012;137:106-112.
47.
Ginzburg K, Ein-Dor T, Solomon Z: Comorbidity of posttraumatic stress disorder, anxiety and depression: a 20-year longitudinal study of war veterans. J Affect Disord 2010;123:249-257.
48.
O'Neil KA, Podell JL, Benjamin CL, et al: Comorbid depressive disorders in anxiety-disordered youth: demographic, clinical, and family characteristics. Child Psychiatry Hum Dev 2010;41:330-341.
49.
Muller JE, Koen L, Stein DJ: Anxiety and medical disorders. Curr Psychiatry Rep 2005;7:245-251.
50.
Hicks DW, Raza H: Facilitating treatment of anxiety disorders in patients with comorbid medical illness. Curr Psychiatry Rep 2005;7:228-235.
51.
Clarke DM, Currie KC: Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med J Aust 2009;190:54-60.
52.
Klein DF: False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 1993;50:306-317.
53.
Crowe RR, Noyes R, Pauls DL, et al: A family study of panic disorder. Arch Gen Psychiatry 1983;40:1065-1069.
54.
Torgerson S: Genetic factors in anxiety disorders. Arch Gen Psychiatry 1983;40: 1085-1092.
55.
Crowe RR, Goedken R, Samuelson S, et al: Genomewide survey of panic disorder. Am J Med Genet 2001;105:105-109.
56.
Stein DJ, Scott K, Haro Abad JM, et al: Early childhood adversity and later hypertension: data from the World Mental Health Survey. Ann Clin Psychiatry 2010;22:19-28.
57.
Scott KM, Von Korff M, Angermeyer MC: The association of childhood adversities and early onset mental disorders with adult onset chronic physical conditions. Arch Gen Psychiatry 2011;68:838-844.
58.
Kroenke K, Jackson JL, Chamberlain J: Depression and anxiety disorders in patients presenting with physical complaints: clinical predictors and outcome. Am J Med 1997;103:339-347.
59.
Diagnostic and Statistical Manual of Mental Disorders, ed 5. Arlington, American Psychiatric Association, 2013.
60.
Bruce S, Machan J, Dyck I, et al: Infrequency of ‘pure' GAD: impact of psychiatric comorbidity on clinical course. Depress Anxiety 2001;14:219-225.
61.
Andresscu C, Lenze EJ, Dew MA, et al: Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study. Br J Psychiatry 2007;190:344-349.
62.
Goes FS, McCusker MG, Bienvenu OJ, et al: Co-morbid anxiety disorders in bipolar disorder and major depression: familial aggregation and clinical characteristics of co-morbid panic disorder, social phobia, specific phobia and obsessive-compulsive disorder. Psychol Med 2012;42:1449-1459.
63.
Levy RL, Olden KW, Naliboff BD, et al: Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 2006;130:1447-1458.
64.
Drossman DA, Toner BB, Whitehead WE, et al: Cognitive-behavioral therapy versus education versus desipiramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 2003;125:19-31.
65.
Lachner JM, Morley S, Dowzer C, et al: Psychological treatments for irritable bowel syndrome: a systematic review and meta-analysis. J Consult Clin Psychology 2004;72:1100-1113.
66.
Spies G, Asmal L, Seedat S: Cognitive-behavioural interventions for mood and anxiety disorders in HIV: a systematic review. J Affect Disord 2013;150:171-180.
67.
Wulsin LR: Is depression a major risk factor for coronary disease? A systematic review of the epidemiologic evidence. Harv Rev Psychiatry 2004;12:79-93.
68.
McDonald-Haile J, Bradley LA, Bailey MA, et al: Relaxation training reduces symptom reports and acid exposure in patients with gastroesophageal reflux disease. Gastroenterology 1994;107:619-620.
69.
Acosta F: Biofeedback and progressive relaxation in weaning the anxious patient from the ventilator. Heart Lung 1988;17:299-301.
70.
Yorke J, Fleming SL, Shuldham CM: Psychological interventions for adults with asthma. Cochrane Database Syst Rev 2006;1:CD002982.
71.
Kellerman J, Zeltzer L, et al: Adolescents with cancer: hypnosis for the reduction of the acute pain and anxiety associated with medical procedures. J Adolesc Health Care 1983;4:85-90.
72.
Richardson J, Smith JE, McCall G, et al: Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions. J Pain Symptom Manage 2006;31:70-84.
73.
Creed F, Fernandes L, Guthrie E, et al; North of England IBS Research Group: The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology 2003;124:303-317.
74.
Saarto T, Wiffen PJ: Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2005;4:CD005454.

Send Email

Recipient(s) will receive an email with a link to 'Comorbidity of Mental and Physical Disorders > 81 - 87: Anxiety and Related Disorders and Physical Illness' and will not need an account to access the content.

Subject: Comorbidity of Mental and Physical Disorders > 81 - 87: Anxiety and Related Disorders and Physical Illness

(Optional message may have a maximum of 1000 characters.)

×
Close Modal

or Create an Account

Close Modal
Close Modal