Anxiety,Health Risk Factors,and Chronic Disease

Abstract

Anxiety disorders are the most common mental health condition and frequently co-occur with a variety of health risk factors, such as physical inactivity, cigarette smoking, and alcohol consumption. As such, untreated anxiety and increased risk for engagement in these health risk habits can further increase risk for later-onset chronic disease and complications in disease management. Contemporary studies have identified unique temporal relationships between the onset of specific anxiety disorders with smoking and alcohol use disorders. Incorporating exercise with evidence-based treatments for anxiety is emerging and promising in enhancing treatments for anxiety-related conditions. Likewise, substance use treatment programs may benefit from the detection and management of anxiety. Collaborative care models for anxiety may provide the needed systems-based approach for treating anxiety more effectively in primary and specialty care medical settings. Based on a qualitative review of the literature, this article summarizes the current research on the associations between anxiety, health risk factors, and the risk for chronic diseases. The authors also offer suggestions for future research that would help in better understanding the complex relationships between the role anxiety plays in the vulnerability for and management of physical inactivity and substance use.

Keywords

anxiety physical inactivity smoking alcohol chronic disease

Although considerable research has investigated the impact of depression on physical health, the past 2 decades have witnessed increased attention to examining the complex associations between anxiety and modifiable health risk behaviors.

Introduction

Anxiety disorders are the most common mental health condition in the United States, with an estimated 28% of individuals meeting clinical criteria for a lifetime anxiety disorder diagnosis.^1,2 Anxiety disorders are costly conditions, with an estimated annual economic burden of $42 billion as a result of impairments in personal, social, and occupational domains.^3-5 Anxiety disorders also tend to have an early onset and chronic developmental course⁶ and are associated with an overall low quality of life.^7-9 In spite of anxiety disorders being among the most treatable mental health disorders, many individuals with clinical anxiety often do not seek care, experience long delays before engaging treatment, or obtain substandard or non–evidence-based care.¹⁰

The public health impact of anxiety disorders is also evident in research documenting consistent associations between anxiety, health risk factors, and chronic disease.^4,5 Relative to medical patients without anxiety, increased physical symptom burden, recurring medical visits, poor self-care and treatment compliance, high medical costs, and worsening mortality are among the many negative consequences of inadequately managed anxiety disorders in the context of chronic disease. However, chronic disease management can be improved through early detection and effective treatment of anxiety. Likewise, changes in specific health behaviors, such as exercise and discontinuing substance use, can be associated with improvement in anxiety-related symptoms and impairments.

This article will first summarize the empirical literature on the association between anxiety and specific health risk factors, such as physical inactivity, nicotine use, and alcohol consumption. Next, we will review the relationship between anxiety and chronic diseases, including cardiovascular disease (CVD), diabetes, and asthma. Finally, we will propose future implications for the detection and management of anxiety through the modification of specific lifestyle factors in primary care treatment settings.

Anxiety and Health Risk Factors

Anxiety and depression are unique, differential emotional states that commonly co-occur in the clinic setting. Anxiety is largely viewed as an upregulating emotion, characterized by sympathetic nervous system activation, heightened startle, hypervigilance, worry, and escape/avoidance action tendencies. Depression, conversely, can be conceptualized as a downregulating emotion, evidenced by fatigue, amotivation, anhedonia, perceived hopelessness and helplessness, and withdrawal/disengagement behavior. Although considerable research has investigated the impact of depression on physical health, the past 2 decades have witnessed increased attention to examining the complex associations between anxiety and modifiable health risk behaviors. Cardinal symptoms of anxiety may also be maintained and regulated by physical inactivity, cigarette smoking, and alcohol consumption. Cross-sectional and longitudinal studies have helped identify unique relationships between symptoms and disorders of anxiety and these health risk factors.

Physical Inactivity

Rates of physical inactivity and sedentary lifestyles are escalating in the general US population^11,12 and elevate the risk for a variety of adverse health outcomes.¹³ Physical inactivity is disproportionately higher in certain groups, especially among older, lower income, and ethnic minority populations.^14-16 Several population-based studies suggest that individuals with anxiety disorders are less physically active than their nonanxious counterparts.^17-19 For example, using a nationally representative sample, individuals diagnosed with current specific phobia, social phobia, panic attacks, agoraphobia, and generalized anxiety disorder (GAD) were significantly more likely to endorse engaging in no regular physical activity in comparison to regular physical activity.¹⁸ Adjusted regression models controlling for demographic factors, physical illnesses, and other comorbid psychiatric conditions continued to find lower rates of 12-month anxiety disorders among those who were classified as being regularly physically active, except for GAD. Furthermore, an inverse dose-dependent relationship was found between the frequency of engagement in physical activity and the likelihood of a current anxiety disorder.¹⁸ Likewise, other population-based surveys note that approximately 63% of those diagnosed with an anxiety disorder were classified as physically inactive.²⁰

Relative to the other anxiety disorders, panic disorder has received the most empirical attention regarding the impact of anxiety on physical activity and exercise.²¹ Another population-based study found that the adjusted odds of restricting physical activity was more than 2 times higher among those with panic attacks in comparison with those without panic attacks after controlling for relevant demographics.²² Furthermore, when directly comparing those with panic attacks with those meeting criteria for panic disorder, the panic disorder group was approximately twice as likely to restrict their physical activity. Additional investigations suggest that physical fitness levels may be compromised among those with panic disorder. Specifically, relative to nonanxious patients, those with panic disorder have been found to have lower VO_2max during standardized exercise testing.^23-25 Furthermore, early termination of submaximal fitness testing appears to be significantly more common among panic disorder patients relative to their nonclinical counterparts.^25,26

Anxiety sensitivity (AS), a cognitive risk factor for panic disorder, characterized by somatic hyperfocus and the tendency to interpret physical sensations as dangerous,²⁷ has received increased empirical attention in the study of anxiety and exercise.²⁸ AS may function as a means of amplifying the intensity of uncomfortable exertional symptoms both during and after periods of exercise. Thus, relative to those low in AS, individuals higher in AS would be expected to experience a greater number of physical symptoms during exercise, rate these symptoms as more uncomfortable or dangerous, terminate exercise interventions prematurely, and be more at risk for avoiding physical activity and exercise altogether. Indeed, initial studies have found that higher scores on measures of AS are inversely associated with levels of physical activity.^29,30 Furthermore, a recent study found that self-reported fear during exercise was predicted by an interaction between higher body mass index and higher AS.²⁸

Several studies have also investigated the impact of exercise on regulating symptoms and disorders of anxiety. A meta-analysis of randomized trials on the effect of anxiety reduction with exercise yielded a moderate effect size (d = 0.54), with longer exercise interventions being associated with larger effect sizes.³¹ Both aerobic and anaerobic exercise can be useful in reducing acute symptoms of anxiety,^31-34 although these effects may not be substantially greater than those achieved through other anxiety-management interventions, such as relaxation or meditation.³⁵ Preliminary research has noted that AS scores do decrease significantly across a 2-week exercise trial relative to waitlist control conditions,¹⁹ and higher intensity exercise interventions produce even greater changes in AS than lower intensity regimens.³⁶ Meta-analytic and cross-sectional findings generally suggest an “optimal dosing” for moderate levels of routine physical activity between 21 and 40 minutes per session to produce maximal change in self-reported anxiety.^17,31

In contrast to the extant literature on the mood-regulating effects of exercise on depression, substantially less research has been conducted with anxiety disorders.^37,38 The majority of available studies have largely been conducted with panic disorder. Given that graduated exposure to uncomfortable physical sensations is a standard component of cognitive-behavioral therapy (CBT) for panic disorder,³⁹ strategically delivered exercise interventions offer promise as an adjunctive treatment for panic disorder.²¹ A randomized 10-week trial compared clomipramine, exercise, and placebo response among patients with panic disorder with agoraphobia.⁴⁰ Both clomipramine and exercise yielded significantly greater symptom reduction than placebo, although clomipramine outperformed the exercise condition. Furthermore, there were reductions in self-reported anxiety following engagement in aerobic and anaerobic exercise programs lasting 8 weeks among patients with panic disorder, social anxiety disorder, and GAD.^24,41 A smaller study found that patients with residual symptoms of obsessive-compulsive disorder may also obtain further, sustained symptom reduction following CBT and pharmacotherapy when engaged in moderate-intensity exercise.⁴² The cross-sectional and prospective associations between physical activity and anxiety disorders have been best researched to date in a 4-year investigation with 2548 individuals between the ages of 14 and 24 years. Cross-sectional analyses indicated that routine physical exercise was associated with lower prevalence rates of anxiety disorders; similarly, prospective studies indicated that routine physical activity may offset the incidence of future anxiety disorder onset.⁴³

Neurotransmitter activity thought to underlie the anxiolytic effects of exercise in humans has been investigated in laboratory animal studies. For example, increased serotonin metabolism is evident among rats during and following exercise inductions.^44,45 Similarly, rats show downregulation of GABAa receptor activity in the corpus striatum after periods of exercise.⁴⁶ Although additional refined studies are needed in humans to isolate the neuropathways involved, some preliminary research suggests that exercise may attenuate anxiety specifically through the downregulation of 5-HT2C serotonin receptors.⁴⁷

The potential benefits of exercise as a means for reducing symptoms, improving well-being, serving as a component of graduated exposure, and protecting against future disorder onset are encouraging, but further research in these areas with improved methodologies are clearly indicated. The ability to address such questions could be clearly enhanced by using longitudinal research designs with samples meeting diagnostic criteria for specific anxiety disorders. Given that the longer term course of many anxiety disorders may be characterized by relapsing episodes, the relative protective effects of exercise in offsetting relapse rates could be assessed. Larger sample sizes could also allow for a more refined analysis by isolating the impact of specific forms of physical activity (aerobic, anaerobic), intensity, and duration on state-levels of anxiety and/or AS after controlling for other factors, such as demographics, baseline levels of physical activity and exercise, and psychiatric comorbidities.

Cigarette Smoking

Epidemiological studies suggest that current and lifetime psychiatric disorders are associated with disproportionately high rates of cigarette use.^48,49 Elevated cigarette smoking is consistently observed among those with clinically significant anxiety symptoms.⁵⁰ Findings from the National Comorbidity Survey indicate that lifetime smoking rates were substantially lower among those without a psychiatric disorder (39%) in comparison with those diagnosed with social phobia (54%), agoraphobia (59%), panic disorder (61%), posttraumatic stress disorder (PTSD; 63%), and GAD (68%).⁴⁸ Likewise, current smoking rates were approximately twice as common among those with PTSD and GAD in comparison with individuals without an anxiety disorder.⁴⁸ Other cross-sectional studies similarly yield rates of anxiety disorders that are 1.5 to 3 times higher among lifetime smokers relative to nonsmokers.^51,52

Nicotine dependence, a more severe marker of nicotine use, may be present in up to 22% of individuals with anxiety disorders.⁵³ Recent findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) noted that the odds of any current anxiety disorder with cigarette smoking nicotine dependence relative to those without nicotine dependence was 2.75 in models adjusting for quantity of cigarette use, and remained significant at 1.41 in the fully adjusted models after accounting for demographics and other comorbid substance, personality, anxiety, and mood disorders.⁵⁴ The prevalence of nicotine dependence has been found to be significantly elevated among patients with specific phobia^53-55 and PTSD.⁵⁶ However, a substantial body of cross-sectional and prospective research studies have revealed unique associations between nicotine dependence and panic disorder.^50,57,58

For example, the prevalence of panic disorder among patients who are nicotine-dependent smokers is approximately 2.5 times higher than among those without nicotine dependence.^59,60 Similarly, in a large-scale, nationally representative sample, current cigarette smokers with nicotine dependence had a nearly 5-fold increase in panic disorder prevalence relative to those who are not currently using tobacco products.⁵⁴ Rates of current cigarette smoking and heavy smoking (ie, 10 or more cigarettes per day) are also approximately twice as high among patients with panic disorder in comparison with those with other anxiety disorders.⁶¹ Furthermore, relative to nonsmoking panic patients, panic patients who currently smoke also tend to report more severe anxiety symptoms.^62,63

Prospective studies have also revealed that heavier levels of cigarette use are prospectively related to a greater risk for developing panic disorder, GAD, and PTSD.^49,64,65 For example, adolescent heavy cigarette use, operationalized as 20 or more cigarettes per day, has been found to significantly increase the risk for developing panic disorder in early adulthood.⁶⁴ Likewise, daily smoking and heavier smoking are associated with an increased risk for later onset panic attacks and panic disorder.^66-68 Premorbid cigarette smoking and later-onset panic psychopathology appears to be the dominant, directional association given that premorbid panic is not necessarily predictive of later cigarette smoking.⁴⁹ Other age-of-onset studies suggest that approximately 92% of specific phobia and 88% of social anxiety patients report that their anxiety disorder preceded nicotine dependence.⁶⁹ These findings underscore the importance of discriminating among specific anxiety disorders in the temporal sequencing of nicotine dependence onset.

In contrast to the extant literature examining cigarette smoking and anxiety disorders, relatively little research has been conducted with smokeless tobacco products. In the only population-based study, the rate of any current anxiety disorder was approximately 3 times higher among smokeless tobacco users who were nicotine dependent relative to smokeless tobacco users who were not nicotine dependent.⁴⁹ Furthermore, regression models continued to support an increased odds of any anxiety disorder and specific phobia among those who were nicotine-dependent smokeless tobacco users; however, no significant associations emerged between any anxiety disorder and smokeless tobacco users without a history of nicotine dependence.⁴⁹

AS also appears to serve an important role in mediating the anxiety–cigarette smoking relationship. As described earlier, AS is characterized as a cognitive vulnerability factor important in the pathogenesis of anxiety disorders in general and panic disorder in particular. The tendency for those high in AS to respond fearfully to sympathetic nervous system arousal may place an individual at risk for smoking, given the acute nervous system amelioration effects of nicotine.^58,70-72 Acute tobacco use and withdrawal may place an individual at risk for experiencing unusual or uncomfortable physical sensations; likewise, chronic cigarette use can lead to more pervasive physical problems and chronic health conditions that may further sensitize those high in AS to be caught in a vicious cycle of somatic hyperfocus and efforts to regulate these symptoms through ongoing cigarette smoking. Indeed, several researchers have noted strong associations between individuals high in AS and daily cigarette smoking.^58,70-72 Risk for experiencing more clinically relevant panic symptoms is higher among daily smokers high in AS relative to daily smokers low in AS.⁷³ Furthermore, high AS also appears to be predictive of individuals struggling with failed smoking cessation attempts.^74,75 Likewise, individuals high in AS may experience more intense withdrawal symptoms⁷⁶ and more perceived difficulties⁷⁷ during quit attempts.

In spite of the extant literature describing the link between anxiety symptoms, anxiety disorders, and nicotine use, no clinical trials currently exist examining the outcomes of smokers versus nonsmokers with anxiety in evidence-based CBT.⁴⁹ Preliminary work is available related to modifying somatic exposure interventions for smokers with panic disorder,⁶³ although additional randomized outcome trials are warranted given the disproportionate association between cigarette smoking and anxiety.

Alcohol Use

Alcohol use, abuse, and dependence represents a progression of increasingly frequent and intense use of alcohol that leads to compounding functional impairments. Alcohol dependence, deemed to be the most severe form of an alcohol use disorder, is characterized by physical and/or psychological cravings with associated risk for experiencing significant withdrawal symptoms. Previous studies have indicated that only approximately 10% of those with alcohol abuse progress to alcohol dependence.^78,79 Prevalence rates of alcohol abuse and dependence are also higher among men compared with women.⁸⁰ Some studies suggest that men with panic disorder are significantly more likely than women to have a comorbid lifetime alcohol use disorder, whereas women with panic disorder were more likely to have other comorbid anxiety disorders relative to men.⁸¹

Multiple lines of research routinely document significant associations between alcohol use disorders (alcohol abuse and dependence) and disorders of anxiety.^53,82-85 For example, data from the NESARC noted a 12-month prevalence of 13% of any alcohol use disorder with any anxiety disorder.⁵³ Furthermore, among respondents with an alcohol use disorder who had sought treatment within the last year, approximately 33% met criteria for at least 1 anxiety disorder.⁵³ After controlling for relevant demographic variables, significant odds ratios (ORs) emerge between 12-month alcohol use disorders and specific anxiety disorders such as panic disorder (OR = 2.3), GAD (OR = 2.1), specific phobia (OR = 1.8), and social anxiety disorder (OR = 1.6).⁸³ The strength of these associations with anxiety appeared to be fully accounted for in those meeting criteria for alcohol dependence (OR range = 2.3-3.6) as the ORs of any anxiety disorder were not significant with alcohol abuse.⁸³ Once demographic factors and other 12-month psychiatric disorders were controlled, only any anxiety disorder remained significant with alcohol use disorders (OR = 1.3) and alcohol dependence (OR = 1.5), underscoring the likelihood that various psychiatric disorders may share common mediating factors.⁸³

When considering the lifetime association between alcohol use and anxiety disorders after controlling for demographic characteristics in the NESARC study, the ORs were all significant, with panic disorder with agoraphobia yielding the highest OR of 2.5.⁸³ As observed in the 12-month data, the significant associations appear to be mostly driven by alcohol dependence, although specific phobia (OR = 1.2) and any anxiety disorder (OR = 1.2) retained a small, but significant relationship. Once controlling for sociodemographics and other lifetime psychiatric disorders, specific phobia, social anxiety disorder, and panic disorder with agoraphobia were significant with any alcohol use disorder, and specific phobia and panic disorder with agoraphobia were significant with alcohol dependence in the fully adjusted models.⁸³ Data from the National Comorbidity Survey-Revised (NCS-R) have also yielded significant associations between lifetime anxiety and alcohol use disorders.⁸⁶ However, in contrast to the NESARC, the observed ORs tended to be higher among alcohol abuse rather than alcohol dependence disorders. The ORs for lifetime alcohol dependence and abuse were strongest for PTSD at 3.8 and 4.6, respectively.⁸⁶ In the NCS-R data, ORs were also calculated among those meeting lifetime criteria for panic attacks without panic disorder. In this group, comparable ORs between panic attacks and alcohol dependence (OR = 2.7) and abuse (OR = 2.9) emerged. Differential patterns of findings between the NCS-R and NESARC analyses may be partially accounted for by the fact that the NCS-R did not control for sociodemographic factors or comorbid lifetime psychiatric conditions and also by the fact that the sample size used by the NESARC was substantially larger.

In a 10-year follow-up study to original NCS participants, alcohol use was significantly associated only with specific phobias and any anxiety disorder.⁸⁷ Although no anxiety disorders were longitudinally associated with a significant increased odds of alcohol abuse, several anxiety disorders (panic disorder, social anxiety disorder, PTSD, separation anxiety disorder, and any anxiety disorder) were all significantly associated with higher ORs of alcohol dependence later in life.⁸⁷ Data from the NCS highlight the importance of separating out alcohol abuse from alcohol dependence when examining specific relationships with anxiety disorders because anxiety disorders appear to be more specifically associated with alcohol dependence, the most severe manifestation of alcohol use disorders.

Prospective studies using age-of-onset data offer important insights into the temporal associations between alcohol use and anxiety disorders.⁸⁷ Some studies have found that premorbid anxiety disorders, but not depressive disorders, increase the risk of later-onset alcohol use disorders.⁸⁸ Other authors have observed temporal relationships in both directions, with preexisting alcohol use disorders increasing risk for anxiety disorder onset and vice versa.⁸⁹ Data from the NESARC have revealed more refined temporal associations between specific anxiety disorders with alcohol use disorders. For instance, alcohol dependence was significantly more likely to precede panic disorder and GAD onset, whereas specific phobia and social anxiety disorder are more likely to precede alcohol dependence onset.⁹⁰ Among those with lifetime alcohol abuse, the same pattern of onset associations emerged, although panic disorder with agoraphobia also appeared more likely to occur after the establishment of alcohol abuse.⁹⁰ Data from the NCS-R also support these unique temporal associations observed in the NESARC. For example, the vast majority of specific phobia (93%) and social anxiety disorder (90%) patients report that the onset of their anxiety preceded the onset of alcohol dependence; however, among patients with panic disorder, GAD, and PTSD only 40% to 50% of the time did these conditions precede the onset of alcohol dependence.⁶⁹ Taken together, these findings indicate that anxiety disorders known for an earlier developmental onset appear to serve as a directional, premorbid risk factor for later onset alcohol dependence.

In contrast to studies investigating exercise and nicotine, substantially less research has been conducted with regard to understanding the role played by AS in regulating alcohol use. In the only prospective study, individuals high in AS were significantly more likely to develop alcohol use disorders 2 years later.⁹¹ Smaller cross-sectional designs have suggested that the suppression of physiological responses by alcohol may be a particularly strong motive among anxious individuals high in AS.⁹² Support for this observation has been found in research noting reduced reactivity to experimentally induced hyperventilation among high AS individuals given acute administration of alcohol.⁹³ However, the intoxicating and unpleasant physiological sensations of alcohol could possibly lead those high in AS to avoid using such substances.

The presence of anxiety disorders among patients seeking treatment for alcohol problems can be considerable. The presence of untreated anxiety may be predictive of relapse and poor compliance with substance abuse treatment programs.⁹⁴ Conflicting results have been reported in the empirical literature regarding the presence of anxiety disorders on alcohol use treatment outcome. Some studies have found higher relapse rates for alcohol-dependent patients with an anxiety disorder in comparison with those without a comorbid anxiety disorder^95,96; however, a larger, more methodologically sound trial indicated that the relapse rates among alcohol-dependent patients following substance use treatment were not higher among anxious patients (social anxiety disorder and panic disorder with agoraphobia) relative to patients without anxiety comorbidity.⁹⁷ Similarly, other researchers have found that significant reductions in anxiety symptoms over the course of an alcohol dependency treatment program did not yield better outcomes.⁹⁸Additional research with prospective designs are needed to better understand the impact of treated versus untreated anxiety disorders among patients seeking treatment for alcohol use disorders.

Anxiety and Chronic Disease

Complex associations exist between anxiety, health risk behaviors, and chronic diseases. Several studies have noted that anxiety disorders are disproportionately higher among patients with chronic illnesses relative to their healthy counterparts and that medical patients with untreated anxiety disorders suffer worsening functional impairments, morbidity, and mortality.⁵ CVD, diabetes, and asthma are 3 such chronic medical conditions that share disproportionately high associations with anxiety disorders.

CVD has been the leading cause of death in the United States for more than a century. Psychiatric disorders have now been recognized as important risk factors to consider alongside other traditional risk factors, such as age, sex, body mass, hypertension, diabetes, physical inactivity, smoking, and familial history of CVD.⁹⁹ Symptoms and disorders of anxiety have been found to be related to risk for developing CVD. For example, anxiety disorders are associated with a 1.5- to 8-fold increase in incident CVD.¹⁰⁰ Within the range of anxiety disorders, phobic disorders, panic disorder, and PTSD appear to show the strongest relationship with CVD.^101-103 Cardiac disease with co-occurring anxiety also tends to predict poor prognosis and disease progression. For instance, anxiety symptoms, such as chronic worry, restlessness, hypervigilance, and panic attacks, are related to poor cardiac functioning, adverse cardiac events, compliance problems with medical treatment, and mortality.^104-106

Diabetes, an escalating public health concern, also appears to be correlated with anxiety disorders. Rates of anxiety disorders are approximately 2 times higher among type 1 and 2 diabetic patients relative to their nondiabetic counterparts.^107-109 The severity of and impairment from diabetic complications are also associated with more intense symptoms of anxiety.^110-112 In contrast to research documenting the significant association between depression and poor glycemic control, mixed results have been found on this dimension among patients with anxiety disorders.^107,113

Asthma is the most prevalent chronic health condition for patients younger than 18 years and can be associated with substantial impairments and adverse health outcomes. Higher rates of anxiety disorders have been found to be reliably associated with asthma prevalence, asthma severity, and poor asthma control. For example, relative to the general population, anxiety disorders are 3 times more common among asthma patients, with panic disorder, panic attacks, GAD, and specific phobias being the most frequently occurring conditions.^114-116 Furthermore, more severe asthmatic presentations are also found among patients with a co-occurring anxiety disorder.¹¹⁵ Other markers of poor asthma control, such as more frequent bronchodilator use, avoidance of physical activity, cigarette smoking, and more frequent emergency room visits and inpatient hospitalization days, also appear to be disproportionately elevated among anxious patients.^117-119

Effective management of CVD, diabetes, and asthma requires significant levels of daily self-care, motivation to assume changes in lifestyle habits, and a willingness to collaboratively engage health care providers. Clinical and subclinical anxiety produces excess sympathetic arousal, somatic hyperfocus, catastrophic styles of thinking, and behavioral avoidance, all of which can interfere with the ability and motivation to consistently assume appropriate levels of disease management. Given that patients with chronic illness frequently present in primary care, have high rates of anxiety-related conditions, and assume greater cost with worse functional outcomes when anxiety goes untreated, opportunities exist in improving the detection and management of anxiety in the applied medical setting.

Collaborative care models involve tailoring the delivery of evidence-based pharmacotherapy and CBT treatments for anxiety in a manner suitable for the nature and demands of the primary care environment.¹²⁰ Treatments for these conditions are designed to remain within primary care, with physicians supported by clinical case managers to deliver interventions, track patient adherence, and assess treatment response. Such interventions targeting the anxiety could be delivered in person before scheduled clinic visits, over the phone, by e-mail, or through secured website access. Improved self-care, lowered symptom burden, improved health-related quality of life, greater compliance, and reduced overall medical costs have been routinely demonstrated when applying collaborative care models for patients with CVD, diabetes, and asthma.^121-123 Anxiety disorders, such as panic disorder and GAD, managed within a collaborative care system, produce similar beneficial psychiatric and health outcomes.^124,125

Future research will continue to investigate how early screening, detection, and evidence-based treatment delivery for anxiety can reduce symptom burden and improve clinical outcomes in chronic diseases and offset incident rates of chronic diseases. Personal and systems-based barriers exist in establishing and maintaining routine access to health care and adherence to recommended interventions. Advances in technology, especially with secure access Web sites, offers a unique opportunity for primary care clinics to further explore the delivery and effectiveness of evidence-based interventions for anxiety in the context of chronic disease. Augmenting an individual’s usual care with Web-based interventions may also be seen as a more preferable modality of contact among some patients, especially given the role avoidance behavior can play in maintaining anxiety impairments across time.

Although collaborative care models have been investigated with specific disease populations, it is important to note that, often, these chronic health problems, and associated health risk behaviors, covary with one another. The overall burden of disease management can become increasingly serious and complex, which can be further compounded by the presence of a clinical anxiety disorder. The importance of further exploring integrated health behavior treatment models that account for the potential longer term management of multimorbidity cannot be overestimated. The feasibility and cost-effectiveness of such collaborative care systems will also continue to be important areas for further scrutiny in dissemination efforts.

Implications and Recommendations for Future Research

Cross-sectional and prospective research studies support the significant relationships between anxiety symptoms/disorders, health risk factors, and chronic diseases. Although considerable knowledge has been generated from these investigations, only recently have we started to gain a better understanding as to how exercise promotion, modification of substance use, and chronic disease management can be influenced by the evidence-based treatment of anxiety. Likewise, emerging studies have started to incorporate prescriptive exercise programs as an adjunct to evidence-based anxiety interventions.

Pharmacotherapy and CBT are well established first-line treatment options for anxiety; yet many patients do not access these treatments.¹²⁴ Exercise interventions offer promise as a portable, easily disseminated treatment option that may be viewed as highly acceptable by patients with anxiety in primary care.²¹ Population-based dissemination efforts have explored the use of the Internet to facilitate exercise interventions¹²⁶ and computer-based CBT programs for anxiety disorders.^125,127 As such, future studies will need to assess the benefits of expanding online anxiety treatment programs with modules addressing prescriptive exercise. Furthermore, the augmentation of exercise interventions with pharmacotherapy and CBT may also help reduce premature dropout from traditional first-line interventions for anxiety. Additional randomized trials with longer term follow-up are needed to determine if exercise-based interventions for the range of anxiety disorders can lead to improved clinical outcomes and reduce relapse rates.

The self-medication hypothesis may partially explain the unique associations between anxiety disorders and substance misuse.^69,128 According to this approach, substance use and anxiety symptoms form a progressively more contingent relationship across time based on the capacity for substances to regulate mood, promote behavioral disinhibition, and reduce physical and cognitive discomfort generated by anxiety. Evidence-based behavioral treatments for anxiety contain many principles to manage problematic substance use, including motivational enhancement, stimulus control, emotion regulation, cognitive restructuring, behavioral activation, graduated exposure, and relapse prevention. For example, individuals with social anxiety may smoke cigarettes as a means of quelling nervousness (ie, negative reinforcement through the removal of an unpleasant state), which in turn, may give them greater confidence in conversing with others in social situations (ie, perceived safety signal). The prospect of not smoking in these situations can provoke increased somatic arousal, catastrophic doubts regarding their ability to confidently interact with others, and urges to avoid these situations. A CBT case formulation would highlight how cigarette use has formed an increasingly contingent relationship with the anxiety, and interventions would be designed to develop behavioral skills to manage uncomfortable physical sensations (eg, progressive exercise, interoceptive exposure, and/or relaxation training), social skill building, testing and challenging beliefs about social competency and ability to “perform” without cigarettes, and gradual exposure to anxiety-relevant situations. Continued exploration of the role of AS as a predictor of treatment response in substance use programs is warranted. Furthermore, additional studies are needed to determine if the behavioral treatment of AS directly adds any incremental effectiveness in the management of nicotine and alcohol use disorders.

Although theoretically the evidence-based management of anxiety in substance use programs may improve treatment outcome and relapse rates, available outcome studies are equivocal. Motivational enhancement strategies, however, do appear to be important components in evidence-based approaches to managing substance-related disorders, and such interventions can be adapted for use in primary care settings.⁸⁰ An important empirical question to address is whether the treatment of comorbid anxiety among substance users confers any incremental efficacy above those achieved through motivational enhancement interventions. Furthermore, nearly 80% of those who are alcohol dependent are also daily cigarette smokers,^129,130 and thus, these health risk behaviors, along with physical inactivity, are likely to present comorbidly. Integrated treatment models need to be developed and tested in an effort to address these concurrent health risk behaviors that invariably complicate anxiety and chronic disease management.

Brief assessments of anxiety have been developed for use in primary care treatment settings. Two such measures, the Overall Anxiety Severity and Impairment Scale (OASIS)¹³¹ and the Generalized Anxiety Disorder-7 (GAD-7),^132,133 have been specifically designed, normed, and implemented into routine medical settings to provide a sensitive and reliable assessment for the potential presence of clinically relevant anxiety. Those responses meeting or exceeding established cutoffs for clinical relevance can then cue the physician or nursing staff to ask additional questions about degree of functional impairment, persistence of symptoms, and willingness to explore evidence-based anxiety treatment options. Furthermore, these measures can be used as an index of change and response to treatment across time. Increased use of such instruments will be an important step toward identifying anxiety in the context of health care management. Furthermore, given that specific anxiety disorders, such as specific phobias and social anxiety disorders, present early in life and show a temporal risk with later onset nicotine⁶⁹ and alcohol⁹⁰ dependence, the importance of detecting and managing anxiety in pediatric treatment settings is imperative.

Conclusion

Anxiety disorders are common, costly, yet treatable mental health conditions. They frequently co-occur with lifestyle habits, such as physical inactivity, cigarette smoking, and alcohol consumption, which increase the risk for later-onset chronic disease. Opportunities exist for augmenting evidence-based treatments for anxiety with behavioral and motivational enhancement strategies that can increase engagement in routine physical activity and reduce the use of substances. Front-line health care providers should advocate for collaborative care models for anxiety to be integrated into the primary care setting to improve health outcomes and reduce the burden of chronic diseases and their risk factors. AJLM

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