Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 48, Num. 4, 2002, pp. 317-321

Journal of Postgraduate Medicine, Vol. 48, Issue 4, 2002 pp. 317-321

Evaluating and Treating Anxiety Disorders in Medical Settings

Ball S, Goddard A, Shekhar A

Department of Psychiatry, Indiana University School of Medicine, 1710 N. Capitol Ave., C-200, Indianapolis, IN 46202, USA.
Address for Correspondence: Anantha Shekhar, M.D., Department of Psychiatry, 1111 W. 10^th Street, 313, Indianapolis, IN 46205, USA E-mail: ashekhar@iupui.edu

Code Number: jp02106

Abstract:

Anxiety disorders and medical illness present to the primary care physician as a common comorbidity. This article aims to review the literature on the prevalence of anxiety disorders in patients presenting to primary care physicians; to address the key issues in assessing the comorbid condition; and to discuss psychological and pharmacological treatment options for patients with a comorbid anxiety disorder and medical illness. Anxiety disorders are highly prevalent within the primary care population, and these disorders significantly impact the patient's course and outcome. Fortunately, primary care physicians have a variety of effective cognitive, behavioral and pharmacological interventions available for managing these patients with comorbid anxiety and medical illnesses. (J Postgrad Med 2002;48:317-321)

Key Words: Anxiety disorders; medical comorbidity; treatment of anxiety

Anxiety as a symptom and as a disorder often presents first in the primary care medical setting. In this report, we review the literature regarding the prevalence of anxiety disorders within the population presenting to primary care physicians; consider the interplay between anxiety and medical symptoms in assessment and evaluation; and discuss psychological and pharmacological treatment strategies, using case examples, for comorbid anxiety and medical conditions.

Prevalence of Anxiety and Medical Comorbidity

Recent studies examining mental health issues within primary care patients have demonstrated significant prevalence of major anxiety disorders. In the RAND Health study,¹ panic disorder, generalised anxiety disorder (GAD), and phobias were assessed within primary care patients who had coronary heart disease, hypertension, diabetes, or depression, either clinical or sub-threshold. In the 2494 subjects, the prevalence of any anxiety disorder ranged from 14.6% among patients with hypertension to 66.3% among patients being treated for depression. Generalised anxiety disorder was found in approximately 10-12% of patients with heart disease, hypertension, or diabetes. Lifetime prevalence rates for anxiety disorders ranged from 28% for heart disease patients to 74.3% for depressed patients. Despite this degree of Comorbidity, the majority of the patients felt that their primary care physician was not addressing their anxiety.

Studies examining specific medical conditions have also demonstrated significant Comorbidity rates.² Among cardiac patients, prevalence rates were cited that 83% of patients with cardiomyopathy meet the criteria for panic disorder whereas 16% of post-myocardial infarction patients have a panic disorder. Panic and respiratory illness often overlap as 24% of patients with chronic obstructive pulmonary disease also have panic disorder.² Similarly, in another study, 54 patients with peripheral vestibular disorder were followed-up for a 3-5 year period. Twenty-five percent of these patients reported psychiatric symptoms prior to the onset of vestibular symptoms. ³ Fifty percent of the patients met the criteria for a psychiatric disorder following the onset of their vestibular symptoms, either panic disorder, major depression, or dysthymia.

The comorbidity between anxiety disorders and medical illness is not only a diagnostic issue, but also has implications for the course of the disease and its outcome. In one study, 222 patients were followed for 12 months post-myocardial infarction.⁴ Major depression, depressive symptoms, anxiety symptoms and history of depression significantly predicted further cardiac complications. A person who recently had a myocardial infarction (MI) and was also anxious was 3.3 times more likely to have further cardiac events (primarily acute coronary syndrome) than a post-MI subject without anxiety. In the Medical Outcomes Study, 875 primary care patients were followed for two years.⁵ Patients with comorbid anxiety and a medical condition had significantly poorer physical and emotional functioning. For example, hypertensive and diabetic patients with anxiety illness functioned similarly as patients with heart disease or depression. In the National Medical Expenditure study, 4% of the 20,000 persons surveyed reported anxiety associated with a medical condition.⁶ The presence of anxiety independently contributed 3.8 additional bed days, even after accounting for demographic characteristics and severity of the medical condition.

Assessment of Anxiety Within Medical Conditions

Given the implications of Comorbidity between anxiety and medical illness, the question that comes up is whether there is a shared relationship underlying the conditions. Anxiety symptoms may result as a physical or as a psychological consequence of a medical illness. Physiological causes of anxiety should be particularly suspected when the timing of the anxiety symptoms occurs in the immediate context of the medical illness. As shown in Table 1, several medical conditions may underlie anxiety symptoms and must be differentially diagnosed.^7,8 Factors that are useful to consider in the differential diagnoses include whether the symptoms are acute or chronic; age of presentation; a previous lack of psychiatric history in the context of similar stressors; and presence of family psychiatric history. Primary anxiety disorders typically present in early adulthood, their onset occurs in the context of psychosocial stressors; they may have exacerbations but are chronic if untreated, and they are often associated with a family history of anxiety or affective disorder or substance abuse.

If anxiety symptoms were due to the underlying medical conditions, then one would expect that treatment of the illness should result in alleviation of the anxiety symptoms. However, the development of a medical illness can also be a vulnerability factor for the subsequent onset of an anxiety disorder. Several risk factors may predispose persons to develop problems with anxiety following a medical illness. These factors include the type of medical condition, pre-morbid adjustment, the person's support system, and psychological somatic sensitivity. Given that anxiety occurs as a response to perceived threat, the presence of a medical condition could result in a person feeling increasingly vulnerable due to fear of loss of physical functioning, loss of autonomy, or possible death. Medical illnesses where the diagnosis is uncertain or the prognosis is ambiguous are likely to exacerbate these fears, resulting in the onset of anxiety disorders.

Personality variables such as somatic amplification⁹ and anxiety sensitivity¹⁰ are additional processes that can interplay with medical conditions to develop anxiety. Somatic amplification occurs in which a person has a hypervigilance or heightened attentional focus on bodily symptoms. Weak or infrequent sensations become amplified through cognitive and affective reactions, such as a perception that these symptoms herald a recurrence or exacerbation of the medical illness. Anxiety sensitivity refers to the propensity to interpret anxiety symptoms as dangerous. Compared to normal controls, patients with anxiety disorders report more fearfulness of anxiety symptoms, such as heart pounding.¹¹ As an example of how these processes can influence each other, consider the case of a cardiac patient. Many cardiac patients report a greater self-awareness of their heartbeat.¹² As they focus on their cardiac symptoms, normal physiological variability can be misinterpreted catastrophically, resulting in the onset of anxiety-related cardiac symptoms, which then further perpetuate the bodily sensations, resulting in a reactive "fear of cardiac" cycle of symptoms.

Comorbid Anxiety and Medical Illness: Psychological Interventions

Cognitive-behavioural treatment strategies have been demonstrated to be highly effective for anxiety disorders, and these interventions can be modified to further address the comorbid relationship between the anxiety illness and medical condition. In this treatment approach, anxiety is viewed as an emotional signal or an "alarm reaction" to indicate that the person perceives something negative as occurring either externally in the environment or internally within his or her body. When anxiety disorders occur in the context of medical illness, the treatment program needs to include specific interventions aimed at "taking away the danger" from their medical illness. A primary intervention is education so that patients may develop a framework for making decisions regarding their symptoms within both a medical and anxiety illness context. Patients may often misunderstand and believe that they are supposed to dismiss their symptoms as "part of my anxiety". Instead, patients need to be empowered so that they are active participants in the medical decision making for understanding the likely source of their symptoms using physician input, environmental factors, predictability, and self-monitoring.

As a case example to illustrate these issues, we treated a 58-year-old female who had a history of two myocardial infarctions. A cardiac defibrillator was implanted to control for arrhythmias, and it had activated on two occasions. Due to the fear of triggering the defibrillator, the patient had become housebound except for doctor's appointments. Within home, she maintained a hypervigilant state over her cardiac condition, e.g., watching her fingertips for colour change. Key elements of the psychological treatment for this patient was exploring the nature of her cardiac symptoms and using her own experience to help differentiate between cardiac-onset versus anxiety-onset symptoms. Further, the defibrillator was reframed from an agent of harm (unpredictable, aversive event) to an agent of protection (facilitating and protecting normal cardiac rhythm). Guidelines that were prudent for monitoring herself were developed within the context of cardiac symptom management, but care was made to not utilise hypervigilance that reinforced her somatic fears. Following the course of treatment, the patient gained greater mobility and resumed social activities.

In the above case, increasing the understanding of the medical illness was a primary intervention for the patient. In other cases, the focus may need to be on decreasing fear of the medical symptom. We treated a 48-year-old female who presented with prominent, persistent dizziness following a mild head concussion. The unresolved dizziness resulted in the onset of panic attacks and avoidance to the extent that the patient was on leave from her work. The patient was treated with a symptom exposure program to habituate her fear of dizziness. Using exercises, such as walking in circles, the patient was able to learn that she retained bodily control and function, e.g., dizziness that increased and then diminished indicated adequate functioning of her vestibular organs. Further, the patient was instructed to reduce reassurance seeking from multiple medical specialists as this behaviour reinforced her fears and did not further alleviate the medical problem.

Comorbid of Anxiety and Medical Illness: Pharmacological Treatments

Anxiety patients with medical comorbidity can be effectively treated with most classes of anxiolytic agents with prescribing modifications taking into account their medical status and its treatment. Cases, in which medication treatment is absolutely contraindicated due to comorbidity are the exception. The indication for anxiolytic pharmacotherapy is often a partial or non-response to an adequate course of cognitive-behavioural treatment. In this context, anxiolytic medication can generally be combined successfully with CBT to enhance treatment effects. Currently, selective serotonin reuptake inhibitors (SSRIs) are considered the first-choice medications for most anxiety disorders due to convincing positive efficacy data across a range of anxiety syndromes including panic disorder, social anxiety disorder, post- traumatic stress disorder, generalised anxiety disorder (GAD), and obsessive compulsive disorder.¹³

Although there is no evidence of differential anxiolytic benefit within the SSRI class, subtle intra-class differences in pharmacokinetic profile can guide prescribing choices in the comorbid patient. For example, some of the SSRIs (e.g. fluoxetine, paroxetine, and fluvoxamine) may inhibit some P450 drug-metabolising liver enzymes, creating the potential for drug-drug interactions in the medically comorbid patient on multiple medications.¹⁴ Sertraline and citalopram appear less likely to affect P450 isoenzymes, and may therefore be more useful for the anxious patient on multiple medications. The SSRIs have no direct effect on cardiac function in routine dose or in overdose, and in this respect are an important advance over the tricyclics, and MAOIs, and thus, are generally safe for anxiety patients with ongoing cardiac disease.

Beyond the SSRIs, several newer psychotropic agents that modify serotonin (5-HT) and norepinephrine (NE) function also have substantial anxiolytic properties. For instance, the 5-HT/NE-reuptake blocker, venlafaxine, is now an important option for patients with GAD, and has the capacity to produce a remission state in this traditionally somewhat treatment-resistant group.¹⁵ Although venlafaxine's safety and side-effect profile are comparable to the SSRIs, one caveat is its tendency to produce mild hypertensive effects (e.g. 10-15 mmHg increments in systolic BP) in some patients. Accordingly, its use in anxious patients with difficult-to-control hypertension and cardiac output limitations as a comorbid condition may be problematic. The 5-HT₂ receptor antagonist, nefazodone, while not yet intensively tested in a variety of anxiety disorders, may be a useful alternative in patients that gain excessive weight during chronic antidepressant treatment. Weight control may become a critical issue for the patient with comorbid diabetes mellitus or coronary artery disease. However, nefazodone should be used cautiously in patients with comorbid liver disease, as cases of severe hepatitis have been associated with its use. Another agent, the 5-HT_1A partial agonist, buspirone has efficacy for GAD, and can be readily used in the comorbid patient. There is little evidence of medically serious side effects or adverse reactions with buspirone, although there is concern that it is a weaker anxiolytic than most of the agents mentioned above.

The major disadvantage of the above 5-HT/NE anxiolytics is delayed onset of therapeutic action (usually 2-4 weeks). In patients with severe anxiety (e.g. the patient with acute panic disorder), this limitation poses a management problem, and the use of benzodiazepine medications may become clinically necessary. Typical anxiolytics include the low-potency benzodiazepines, such as diazepam and lorazepam, as well as the higher potency benzodiazepines, such as alprazolam and clonazepam. Among the benzodiazepines, pharmacokinetic issues, particularly half-life rates and metabolites, are important in selecting an agent for clinical use.¹⁶ Longer-acting high potency agents such as clonazepam, are typically recommended with the thought that the longer metabolic half-life will give more stable therapeutic effects and facilitate tapering at the time of discontinuation. Early, regular co-administration of clonazepam with an SSRI, followed by early taper, permits rapid anxiety symptom stabilisation, but avoids the complication of physiological dependence that accompanies longer-term benzodiazepine treatment.¹⁷

Generally, the benzodiazepines are metabolized in the liver and excreted in the urine. The benzodiazepines that have simpler metabolisms, such as lorazepam or oxazepam, are to be preferred in patients with liver or renal impairment as well as in the elderly. Conversely, low potency benzodiazepines, such as diazepam and chlordiazepoxide, have more active metabolites that can accumulate and result in excessive daytime sedation, cognitive impairment, and balance incoordination or falls, especially within the elderly. Benzodiazepines should also be used sparingly in the anxious patient with severe respiratory disease (e.g. COPD or asthma), those with sleep apnoea, and those with certain neuromuscular diseases such as myasthenia gravis, in whom the sedative and muscle-relaxant properties of the benzodiazepines could contribute to worsening of the medical symptoms. Some GABA-ergic anti-convulsants, such as sodium valproate and gabapentin, appear to control the severe symptoms of panic and social anxiety disorder, and have gained popularity as treatment options for these conditions, based on several pilot clinical trials.¹⁸ Definitive large-scale trials are attempting to assess the potential of these new class of anxiolytic agents.

Conclusions

The ubiquity of anxiety in the presentation of patients with medical illness warrants additional and close attention to these types of symptoms. In this paper, we have reviewed guidelines for the assessment and treatment of comorbid medical and anxiety illnesses. The complexity of the comorbid condition requires not only consideration of each individual illness, but also their psychological and physiological interactive and synergistic effects. As patients struggle to understand their symptoms and cope with their fears, the primary care physician becomes their best ally in educating them that anxiety is a treatable illness rather than simply a "weakness in character".

References

1. Sherbourne CD, Jackson CA, Meredith LS, Camp P, Wells KB. Prevalence of comorbid anxiety disorders in primary care outpatients. Arch of Fam Med 1996;5:27-34.
2. Cassem EH. Depression and anxiety secondary to medical illness. Psychiatr Clin of North Am 1990;13:597-612.
3. Eagger S, Luxom LM, Davies RA, Coelho A, Ron MA. Psychiatric morbidity in patients with peripheral vestibular disorder: A clinical and neuro-otological study. J Neurol Neurosurg Psychiatry 1992; 55:383-7.
4. Frasure-Smith N, Lesperance F, Talajic M. The impact of negative emotions on prognosis following myocardial infarction: Is it more than depression? Health Psychology 1995;14:388-98.
5. Sherbourne CD, Wells KB, Meredith LS, Jackson CA, Camp P. Comorbid anxiety disorder and the functioning and well-being of chronically ill patients of general medical providers. Arch Gen Psychiatry 1996;53:889-95.
6. Marcus SC, Olfson M, Pincus HA, Shear MK, Zarin DA. Self-reported anxiety, general medical conditions, and disability bed days. Am J Psychiatry1997;154:1766-8.
7. Wise MG, Rieck SO. Diagnostic considerations and treatment approaches to underlying anxiety in the medically ill. J Clin Psychiatry 1993;54:22-6.
8. Marsh CM. Psychiatric presentations of medical illness. Psychiatr Clin of North Am 1997;20:181-204.
9. Reiss, S. Expectancy model of fear, anxiety, and panic. Clin Psychol Rev 1991;11:141-53.
10. Cox, BJ, Parker, JDA, Swinson, RP. Anxiety sensitivity: confirmatory evidence for a multidimensional construct. Behav Res Ther 1996; 34:591-8.
11. Barsky AJ, Ahern DK, Brener J, Surman OS, Ring C, Dec GW. Palpitations and cardiac awareness after heart transplantation. Psychosom Med 1998;60:557-62.
12. Gorman JM, Kent JM. SSRIs and NSRIs: Broad spectrum of efficacy beyond major depression. J Clin Psychiatry 1999;60(Suppl 4):33-8.
13. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 1997;32(Suppl 1):1-21.
14. Sheehan DV. Attaining remission in generalized anxiety disorder: Venlafaxine extended release comparative data. J Clin Psychiatry 2001;62(Suppl 19):26-31.
15. Shader RI, Greenblatt DJ. Use of benzodiazepines in anxiety disorders [see comments]. N Engl J Med 1993;328:1398-405.
16. Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D. Early co-administration of clonazepam with sertraline for panic disorder. Arch Gen Psychiatry 2001;58:681-6.
17. Pande AC, Pollack MH, Crockatt J, Greiner M, Chouinard G, Lydiard RB, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol 2000; 20:467-71.

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