What disorder is most likely to accompany generalized anxiety disorder?

Treatment and Monitoring

Current practice guidelines indicate that the treatment of an anxiety disorder begins with education. Many people are confused, scared, or frustrated by the symptoms and behavior and are reassured to know they are not alone and that there are effective interventions. The patient should receive an appropriate medical workup, such as a physical examination, and studies (e.g., electrocardiogram, thyroid-stimulating hormone) when indicated. After ruling out a medical condition, developing a good working alliance with the patient provides a basis for ongoing disease management and prevents unnecessary utilization or overutilization of the medical system, as well as potential exacerbation of symptoms.

A combination of psychotherapy and medication management is recommended as first-line treatment for GAD. CBT has the strongest empirical support to date for the treatment of anxiety. Mindfulness-based stress reduction (MBSR) has an emerging evidence base as an effective alternative or complementary behavioral treatment program for anxiety. Both offer a skills-based approach to treatment. In CBT, the therapist and patient work collaboratively and in an active and problem-solving manner. It is structured and generally short term with an emphasis on reducing symptoms and preventing “flare-ups” by monitoring and changing unhelpful or inaccurate thinking patterns that result in feelings of anxiety and worry. Another critical component of CBT for GAD is learning and applying behavioral relaxation techniques (e.g., diaphragmatic breathing, guided imagery, progressive muscle relaxation) and distress tolerance skills (e.g., mindfulness, acceptance). Volumes of evidence support the efficacy of CBT interventions for GAD, but success requires commitment to treatment on the part of the patient. Its efficacy is also contingent upon the ability of the therapist and the length of time in treatment. Studies show that when compared with patients undergoing monotherapy, patients treated with a combination of CBT and medication experience nearly twice the remission rate.

SSRIs have been shown to be the best-tolerated class of medication, and response rates are significantly higher than placebo for GAD. SSRI medications includes fluoxetine (Prozac),1 fluvoxamine (Luvox),1 citalopram (Celexa),1 escitalopram (Lexapro), paroxetine (Paxil), and sertraline (Zoloft).1 Some improvement in symptoms should be noted within 3 or 4 weeks, and the dose should be increased if no improvement is seen. In treating any anxiety disorder, SSRIs should be started at low doses and gradually titrated up to therapeutic levels to avoid an initial exacerbation of anxiety. Pharmacotherapy options for the treatment of GAD are presented inTable 1.

Benzodiazepines, which have been commonly used in the past to treat anxiety disorders, are not recommended except in cases of extreme impairment of function and only for very short-term use. The tolerability and lack of addiction potential make the SSRIs more desirable for long-term management, but the delay in response makes short-term symptom relief with a benzodiazepine desirable for those with the greatest impairment. Because of the risk for rebound anxiety when withdrawing from benzodiazepines with short half-lives, such as alprazolam (Xanax), many prefer the longer-acting benzodiazepines, such as clonazepam (Klonopin).1 However, the addiction potential and the potential for abuse with either drug make this the treatment option of last resort.

Abstract

Generalized anxiety disorder (GAD) is characterized by excessive and persistent anxiety and uncontrollable worry that occurs for at least 6 months. GAD is associated with significant and pervasive impairment in broad areas of functioning, such as lost productivity at work, interpersonal problems, and increased utilization of medical services. Moreover, the course of GAD appears to be chronic and relatively unremitting, with the majority of patients reporting an early age of onset. This article provides an overview of GAD and discusses its phenomenology, etiology, conceptual models, and treatment approaches including psychodynamic, cognitive–behavioral, emotion-focused, integrative, and pharmacological therapies.

Diagnosis

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When diagnosing treatment resistant GAD, it is imperative to rule out selected medical causes/contributing factors (Table E1).

Screening tests may enhance detection. A screening tool often used in primary care is the GAD-2. It asks, “During the past month, have you been bothered a lot by:

“Nerves or feeling anxious or on edge?”

“Worrying about a lot of different things?” The response to each question is given a score of 0 (not at all), 1 (several days), 2 (more than half of the days), 3 (nearly every day).

A score of ≥3 has a sensitivity of 86% and a specificity of 83% for detecting GAD. A simple 7-item in-office case finding instrument, the GAD-7, includes additional questions to assess symptom severity and can be used to monitor symptoms.6

TABLE E1. Selected Medical Causes of Anxiety

From Stern TA et al:Massachusetts General Hospital handbook of general hospital psychiatry, ed 7, 2018, Elsevier.

Introduction

Generalized anxiety disorder (GAD) is a prevalent disorder (5.1% lifetime prevalence in the US general population) (Wittchen et al., 1994). GAD is commonly associated with psychiatric and medical comorbidities (Hidalgo and Davidson, 2001) and is often chronic. GAD is associated with extensive psychiatric and medical utilization and, if left untreated, can cause impairment as severe as major depressive disorder (MDD) (Greenberg et al., 1999; Kessler et al., 1999a, b; Stein and Heimberg, 2004; Ansseau et al., 2005).

GAD usually presents first to primary care physicians or other specialists rather than to psychiatrists. Awareness of GAD's clinical presentation, high prevalence, impairment, and health costs is important for all clinicians, regardless of their medical subspecialty.

In this chapter we review the epidemiology, clinical features and course, complications, genetics and neurobiology, and the current treatments for GAD.

Definition

Generalized anxiety disorder (GAD) is most likely to present in combination with other psychiatric and medical conditions. Based on DSM-5 criteria, individuals with GAD commonly present with excessive and disproportionately high levels of anxiety, fear, or worry for most days over at least a 6-mo period in a number of areas. The worrying must be greater than would be expected given the situation, and it must cause significant interference in functioning. The subjective anxiety must be accompanied by at least three somatic symptoms in adults and one in children (e.g., restlessness, irritability, sleep disturbance, muscle tension, difficulty concentrating, or fatigue). GAD cannot be diagnosed if it occurs only in the context of an active mood disorder, such as depression, or if the anxiety is better explained by another active anxiety disorder, such as PTSD or panic disorder.

6.19.1 Introduction

Generalized anxiety disorder (GAD) is a chronic anxiety disorder characterized by excessive and uncontrollable worry, which can be resistant to change and results in substantial personal and societal costs. GAD is the most recent edition to the Diagnostic and Statistical Manual (DSM) anxiety disorders, having first been conceptualized under anxiety neurosis due to its diffuse anxiety with the absence of a clear phobic target. Though once considered a residual disorder, GAD has gained recognition as an important stand-alone disorder due to a solid research based documenting its unique features and debilitating consequences.

Abstract

Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders and is highly comorbid with other disorders. GAD is characterized by persistent, excessive and uncontrollable anxiety and worry about everyday life events. Additionally, GAD has been linked to inflexible patterns of cognitive, affective, physiological and neurobiological processes. Individuals with GAD are likely to present with interpersonal difficulties. Theoretical advances in the past two decades have facilitated improvements in treatment efficacy for GAD. Among different treatment approaches, cognitive-behavioral therapy (CBT) has been known to be the treatment of choice for GAD. CBT focuses on the alleviation of anxiety and worry in cognitive, affective and psychophysiological processes of GAD. Future therapy can benefit from treatment component analysis and development of new therapy techniques.

Generalized Anxiety Disorder (GAD)

B Generalized anxiety disorder

Generalized anxiety disorders (GADs) are characterized by a dysfunction in the serotonergic system (Connor & Davidson, 1998). Senkowski, Linden, Zubrägel, Bär, and Gallinat (2003) investigated the LDAEP in unmedicated patients with GAD in order to further elucidate the pathophysiological role of serotonin in the manifestation of GAD. Interestingly, the LDAEP was significantly decreased in patients compared to healthy controls indicating a serotonergic hyperactivity in GAD. The exact role of serotonin in GAD is still not fully understood as both increased and decreased serotonergic activity has been reported in this disease (Connor & Davidson, 1998). However, this finding appears to be contradictory to the efficacy of SSRIs in the treatment of GAD. Senkowski et al. (2003) argued that the therapeutic properties of SSRIs may be due to the enhancement of inhibitory serotonergic afferents blocking other neurotransmitter systems that are related to the pathogenesis of GAD such as noradrenaline, but this hypothesis needs to be clarified in further studies. In medicated GAD patients, LDAEP did not differ from healthy controls (Park, Lee, Kim, & Bae, 2010). A further study examined the treatment response to the SSRI escitalopram in GAD patients depending on the pretreatment LDAEP. Of note, GAD patients with a favorable response to escitalopram (10–20 mg per day) after a treatment period of 8 weeks, as assessed by the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression–Severity Scale (CGI-S), were characterized by a stronger pretreatment LDAEP (Park, Kim, Kim, Im, & Lee, 2011). It has therefore been suggested that the LDAEP may be a useful tool in clinical practice to predict treatment response to serotonergic agents in patients with GAD.

Generalized anxiety disorder

GAD is a chronic and disabling disorder with high health service utilization rates, particularly in the primary care sector. Lifetime prevalence of GAD in the NESARC study was 4.1%, with a 12-month prevalence of 2.1% (Grant et al., 2005). These rates are somewhat lower than those found in the earlier NCS, which documented lifetime prevalence of 5.1% and 12-month prevalence of 3.1% (Wittchen, 2002). Surveys from Scandinavian patients seeing a general practitioner found point prevalence rates of 4.8% for males and 6.0% for females (Munk-Jorgensen et al., 2006). Studies have consistently found that females demonstrate twice the prevalence rates of GAD compared with males (Carter et al., 2001; Wittchen, 2002; Grant et al., 2005). In a large German study, prevalence of subthreshold GAD symptomatology, including feeling worried, tense, or anxious most of the time for at least a month, was 7.8% when viewed over the 12 months prior to the survey (Carter et al., 2001).

Mean age of onset of GAD in the NESARC study was 32.7 years, and respondents with lifetime GAD reported an average of 3.4 episodes during their lifetime. Mean duration of an episode was 11.1 months. Approximately 50% of those respondents with GAD had received treatment specifically for the disorder. Mean age at time of initial treatment was 34.7 years (Grant et al., 2005). GAD is associated with a significant economic burden, owing not only to the direct costs of care, but also to decreased work productivity. In one study, approximately 34% of patients with GAD alone and 48% of these with GAD plus major depression showed a reduction in work productivity of 10% or more. Indeed, 23% of the patients with GAD and major depression experienced reductions of 50% or more in the activities of the previous month (Wittchen, 2002).

Consistently, researchers have found high rates of GAD among primary care clinic patients, e.g., 8% in one study (Wittchen, 2002). Of all patients visiting their primary care physician for a psychological problem, one-quarter met criteria for GAD without a comorbid disorder. In one European study, 22% of all primary care patients who complained of any anxiety symptoms were found to have a diagnosis of GAD. GAD is the most frequent anxiety disorder seen in primary care (Wittchen, 2002). The results of the surveys conducted in Scandinavia, however, found that general practitioners identified only 33–55% of cases of GAD, as measured by a self-report scale. Patients who presented with physical complaints rather than anxiety symptoms were less likely to be identified by general practitioners (Munk-Jorgensen et al., 2006). Primary care studies have found that patients with pure GAD report a twofold higher than average number of visits to a primary care physician compared with depressed patients. GAD ranks third among anxiety disorders, after PTSD and panic disorder, in the rate of use of primary care doctors’ time. Approximately one-third of GAD patients seek medical help for somatic complaints related to GAD (Wittchen, 2002).

Previously, GAD was conceptualized by many to be a prodrome, residual, or severity marker of major depression rather than an independent diagnosis. This was due to the high rates of comorbidity of GAD with other psychiatric illnesses. Earlier epidemiological studies, like the NCS, demonstrated that, although there was prominent comorbidity between MDD and GAD, the two disorders had approximately equal and independent magnitudes of impairment (Kessler et al., 1999). In combination, individuals have higher levels of impairment compared with either disorder alone (Wittchen, 2002). In the NESARC study, GAD was found to be comorbid with nearly every psychiatric disorder studied. GAD was more strongly related to dependence than abuse for alcohol and drug use disorders, with the strongest associations seen for drug dependence. In this study, bipolar I and dysthymia were the mood disorders most strongly related to GAD, and panic disorder with agoraphobia was the anxiety disorder most highly correlated with GAD. Other highly comorbid anxiety disorders included social phobia, specific phobia, and panic disorder without agoraphobia. Several personality disorders were also found to be associated with GAD, including dependent, avoidant, paranoid, and schizoid. In fact, only 10.2% of respondents meeting criteria for GAD in the 12 months prior to the survey did not also meet criteria for another psychiatric disorder (Grant et al., 2005). In the Scandinavian surveys, the point prevalence of comorbid MDD and GAD ranged from 1.8% to 2.8% in males and 1.6–3.5% among females (Munk-Jorgensen et al., 2006). In a German survey, 40.5% of GAD patients had concurrent major depression, 59% had 12-month comorbid major depression, and 60% had lifetime comorbid major depression (Wittchen, 2002).

When those respondents with “pure” GAD, i.e., without a comorbid psychiatric disorder, were compared with respondents with other pure psychiatric illnesses, the results indicated that the disability experienced by the GAD patients was significantly greater than that experienced by respondents with alcohol or drug disorders, other anxiety disorders, or personality disorders. When compared with pure mood disorders, respondents with GAD had approximately equivalent levels of disability. When disability from GAD comorbid with other psychiatric disorders was compared with the disability from these comorbid conditions alone, respondents with GAD and comorbid mood, anxiety, and personality disorders reported significantly greater disability (Grant et al., 2005).

When compared with the oldest age group studied, the prevalence rate of GAD was notably higher among middle-aged adults (30–64 years) in the NESARC study (Grant et al., 2005). This finding validates the NCS study, which found the highest prevalence rate among the 45–55-year age group. Rates among children and adolescents are lower, and onset of GAD prior to age 25 is rare (Wittchen, 2002).

Asian, Hispanic, and black adults had lower odds ratios for GAD compared with whites. Widowed, divorced, and separated adults had higher odds of GAD compared with married or cohabitating adults. Odds of GAD were also significantly higher among the three lowest-income groups, earning less than $69 999, compared with the highest-income group (Grant et al., 2005).