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Supplements Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depre
Implications of an SSRI Generic Step Therapy Pharmacy Benefit Design: An Economic Model in Anxiety Disorders
Patt Ellen Panzer, MD, MPH; Timothy S. Regan, BPharm, RPh, CPh; Evelyn Chiao, PharmD; and Matthew W. Sarnes, PharmD
Adherence to Paroxetine CR Compared With Paroxetine IR in a Medicare-eligible Population With Anxiety Disorders
Matthew S. Keene, MD; Michael T. Eaddy, PharmD, PhD; Winnie W. Nelson, PharmD, MS; and Matthew W. Sarnes, PharmD
Differences in Total Medical Costs Across the SSRIs for the Treatment of Depression and Anxiety
David V. Sheehan, MD, MBA; Michael T. Eaddy, PharmD, PhD; Manan B. Shah, PharmD, PhD; and Robert P. Mauch, Jr, PharmD, PhD
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Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depression
C. Lindsay DeVane, PharmD; Evelyn Chiao, PharmD; Meg Franklin, PharmD; and Eric J. Kruep, PharmD, MS

Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depression

C. Lindsay DeVane, PharmD; Evelyn Chiao, PharmD; Meg Franklin, PharmD; and Eric J. Kruep, PharmD, MS

Anxiety disorders are highly prevalent in adults and often coexist with depression. Patients with anxiety commonly present to their primary care doctors, or in other medical settings, reflecting a high utilization of medical services. Furthermore, some patients initially complain of only somatic symptoms before they are ultimately diagnosed with a primary anxiety disorder. Approaches to management include both nondrug and drug treatments, and pharmacotherapy has substantial evidence-based support for efficacy. Of the drugs available for use, an antidepressant, and in particular a selective serotonin reuptake inhibitor, is the preferred initial treatment for most patients. This choice is based on the drug's proven efficacy, favorable adverse event profile, relative safety in overdose, and better management of comorbid depression. The treatment of anxiety disorders has multiple potential benefits in systems of managed care. These include the ability to maintain remission or prevent relapse, a decrease in comorbid depression, promotion of adherence with improvement in quality of life, and reduction in claims for medical care. This overview of the anxiety disorders sets the stage for subsequent discussions of managed care datasets highlighting the opportunities for making informed decisions about access to care and treatment that can lead to economic benefits, especially in light of the Medicare Modernization Act.

(Am J Manag Care. 2005;11:S344-S353)

This article describes the current burden of anxiety disorders and provides a synthesis of relevant findings in recent scientific literature to assist managed care decision makers in better understanding the importance and impact of anxiety disorders. The authors provide an overview of anxiety disorders with a focus on evidence-based medication management principles in the general population. These comments should help provide insight into special challenges and opportunities in managed care populations. In light of the Medicare Modernization Act (MMA), special attention is focused on unique treatment considerations in the elderly. The remainder of this supplement presents important results from retrospective database studies conducted in large managed care settings. These studies were designed to provide decision makers and clinicians with real-world data to support anxiety and depression treatment decisions and offer a glimpse of what benefits may accrue in comparable treatment settings.



The lifetime prevalence of anxiety disorders is approximately 28.8% in the United States, with more than 1 of every 4 adults experiencing at least 1 anxiety disorder in their lifetime.1 Accordingly, anxiety disorders place a significant economic impact on the US healthcare system. The total annual cost of anxiety disorders has been estimated to be between $42.3 billion and $46.6 billion, of which more than 75% can be attributed to morbidity, mortality, lost productivity, and other indirect costs.2,3 In comparison, the total economic burden of coronary artery disease may be as high as $133.2 billion, whereas that of asthma may be as high as $16.1 billion.4 Even more compelling is that the total cost estimate for anxiety disorders comprises more than 30% of the total expenditures for mental illnesses; the cost of anxiety drug therapy accounts for 53% of the drug expenditures for mental illnesses.3,5

Of special significance to managed care organizations, a majority of frequent users of medical resources have symptoms of anxiety and/or depression. Schmitz and Kruse found that patients with a single anxiety disorder were 56% more likely to be a frequent user of medical services compared with patients with no anxiety disorder, and patients with comorbid anxiety and other psychiatric disorders were more than 3 times more likely to be a frequent user.6 Remarkably, only 10% of frequent users with anxiety account for almost 30% of office visits, more than 50% of outpatient specialist visits, and 48% of days spent in a hospital.7 Given the high resource consumption by this patient population and the significant economic impact they have on the healthcare system, further investigation is warranted into the most clinically appropriate yet cost-effective therapy for patients with significant anxiety and anxiety disorders.

Clinical Presentation of Anxiety Disorders

The clinical manifestation of anxiety can vary widely from nonspecific somatic symptoms to severely debilitating illness. The diagnosis of chronic anxiety disorders can be difficult, because nonspecific or vague symptoms can be masked by other comorbid conditions or may be inadequately described or expressed by the patient. Physical symptoms, such as chest pain, fatigue, headache, insomnia, shortness of breath, dizziness, nausea, palpitations, and numbness, are often nonspecific and may mimic the patient's existing comorbid conditions,5 further complicating the differential diagnosis of an anxiety disorder. Anxiety can also be triggered by underlying medical conditions, such as hypoparathyroidism, pheochromocytoma, or even coronary artery disease.8 Another common precipitant of symptoms of anxiety is the initiation or withdrawal of various drugs, including antipsychotics, corticosteroids, thyroid hormones, and stimulants.5 Comorbidity with psychiatric disorders is common, especially major depressive disorder, but others include multiple anxiety disorders (panic disorder, social anxiety disorder [SAD], post-traumatic stress disorder [PTSD], generalized anxiety disorder [GAD]), and dementia.9 It is important to differentiate chronic anxiety disorders from acute anxiety triggered by life events or stressors or anxiety from other psychiatric conditions.

The majority of patients with anxiety disorder (83%) present to their physician with somatic symptoms, although studies have shown that physicians are less likely to recognize psychiatric illness if presented with physical symptoms alone.5,8 However, the number of physical symptoms reported by the patient may be an indication of an anxiety disorder, with a higher number of symptoms being associated with a higher likelihood of an anxiety disorder.5 Other clues may also help distinguish anxiety disorders from underlying medical conditions. For instance, patients suddenly developing new-onset anxiety symptoms after the age of 35 who have otherwise been in good physical health with no previous symptoms of anxiety should be evaluated for underlying medical conditions. Generally, adult patients experiencing an anxiety disorder are likely to have had an anxious childhood or adolescence.8 Diagnosis of anxiety disorders can be further complicated if patients do not report symptoms associated with anxiety to their physician. This situation can occur when a patient feels there is a negative stigma associated with a mental disorder diagnosis.

Because of the difficulty in recognizing and properly diagnosing anxiety disorders, epidemiological prevalence rates may underestimate the true number of people experiencing an anxiety disorder, which is particularly true in the elderly. For example, Mulsant et al conducted a retrospective cohort study and found that one third to one half of elderly inpatient subjects had severe anxiety symptoms, whereas only 8% had a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-diagnosed anxiety disorder.10,11

Classification of Anxiety Disorders

The term "anxiety disorder" encompasses 5 major disorders defined by the National Institutes of Mental Health. These are GAD, obsessive-compulsive disorder (OCD), panic disorder, phobias, including SAD, and PTSD.12 Additional subtypes are identified by the DSM-IV.13 The most common anxiety disorders are SAD (lifetime prevalence 12.1%), PTSD (6.8%), and GAD (5.7%).1,14 A brief description of the 5 major anxiety disorders is provided in Table 1.


Comorbid Anxiety and Depression

Comorbid anxiety disorders and major depressive disorder (depression) are frequently encountered concurrently; an estimated 85% of patients with depression have symptoms of anxiety, and 58% have a diagnosis for an anxiety disorder during their lifetime.11 The prevalence of comorbid GAD and depression, the most common combination, has been reported in as high as 60% to 90% of patients with GAD in community populations.9 Comorbid anxiety and depression is especially common in the elderly18 and has been associated with significantly greater severity of somatic symptoms and significantly poorer social functioning compared with elderly patients with depression alone.11 These patients also tend to have lower Global Assessment Scale scores and more severe symptoms of depression.11 Additionally, patients with comorbid conditions are more frequent users of medical resources, as demonstrated by Sheehan et al in this supplement and others.6,19


Drug and Nondrug Treatment

In general, 2 types of treatment are available for anxiety disorders–psychotherapy and pharmacotherapy. One or both approaches can be effective depending on the specific anxiety disorder being treated. Psychotherapy, which includes cognitive behavioral therapy (CBT) and collaborative care, has been effective for specific phobias, whereas pharmacotherapy alone or in combination with psychotherapy is generally considered the treatment standard for most anxiety disorders. CBT involves training patients to recognize internal or external stimuli that are associated with feelings of anxiety, altering maladaptive patterns of response to such stimuli, thus allowing patients to reduce their anxiety. Collaborative care, a method of disease management that involves close collaboration between the patient, primary care provider, and behavioral care specialist, has been shown to improve the quality of care and clinical outcomes in certain anxiety disorders, such as panic disorder, although studies are conflicting.20,21

Pharmacotherapy treatment algorithms for anxiety disorders vary based on the specific diagnosis. Anxiolytic agents, of which benzodiazepines and buspirone are the principal members, may be used for acute anxiety relief for a limited period,8 but, in general, patients should begin treatment for chronic anxiety disorder with an antidepressant (either a selective serotonin reuptake inhibitor [SSRI] or a mixed-mechanism antidepressant). A summary of the most recent consensus treatment guidelines is found in Table 2.


Anxiolytics. Anxiolytics have historically been the mainstay of treatment for anxiety disorders. Given their relatively high side effect burden and inconsistent results in reducing symptoms or inducing remission, these agents are no longer recommended as first-line treatment.

Benzodiazepines have been the most widely studied and utilized class of drugs for anxiety disorders and were the treatment of choice for many years.15,16 Their efficacy in reducing somatic symptoms has been documented, but they produce little improvement in the psychic symptoms of anxiety and have questionable efficacy in long-term treatment; studies have shown a reduction in Hamilton Anxiety Scale scores similar to placebo.23 Additionally, benzodiazepines are associated with a higher burden of central nervous system side effects, such as cognitive impairment, psychomotor impairment, and daytime sedation, than other therapeutic options,11 as well as a risk of dependence and producing a discontinuation syndrome.22,24

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