Generalized anxiety disorder (GAD) has received a flurry of research attention in recent years, resulting in new findings that have expanded our understanding of the disorder and its treatment. Many of the latest findings have resulted from new conceptualizations of the nature of GAD with which many mental health professionals are unfamiliar.
In this arricie, we provide a brief description of GAD as it is currently defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and then address several misconceptions about the nature and treatment of GAD that are widely held by mental health professionals. The misconceptions are that: (1) GAD is an innocuous condition that does not lead to significant distress or impairment; (2) effective treatment requires the patient to uncover and work through early traumas; (3) cognitive-behavior therapy (CBT) produces immediate relief of symptoms, but not long-lasting relief; and (4) long-term treatment with benzodiazepines is a benign therapeutic strategy.
In contrast to these misconceptions, we argue that the most recent findings in the literature suggest that: (1) GAD is a clinically significant condition that causes significant distress and functional impairment; (2) effective new CBT does not require patients to excavate and work through early childhood traumas; (3) CBT produces both immediate and long-lasting relief; and (4) the long-term use of benzodiazepines, although effective in treating GAD, poses significant risks.
DESCRIPTION OF GAD
The essential feature of GAD is excessive worry occurring more days than not for at least 6 months. The worry must concern several different domains or activities (eg, work, finances, family, and health) and must be difficult to control. The worry or anxiety must be associated with at least 3 of the following 6 symptoms: (1) restlessness; (2) fatigue; (3) impaired concentration; (4) irritability; (5) muscle tension; and (6) sleep disturbance. The worry must lead to significant distress or impairment. Symptoms must not be due to another Axis I disorder; must not be present solely during the course of a mood disorder, psychotic disorder, or pervasive developmental disorder; and must not be due to a general medical condition or the direct physiological effects of a substance.1 The DSM-IV uses the apt term "anxious apprehension" to describe the typical mental state of these patients. A diagnosis of GAD fits many patients who describe themselves as chronic worriers.
COMMON MISCONCEPTIONS ABOUT GAD
Misconception 1 - GAD Is an Innocuous Condition That Does Not Lead to Significant Distress or Impairment
The diagnostic category GAD appeared for the first time in the DSM-ÌII in 1980, and it was a residual category. That is, if a patient met criteria for another anxiety disorder, that anxiety disorder was diagnosed but GAD was not. Thus, when GAD occurred alone, the DSM-III did not view it as a clinically significant condition.
However, numerous investigations have shown that this perception is incorrect. Many patients with GAD report that they worry more than 50% of their waking day.2 GAD is associated with significant social and occupational disability. Wittchen et al.3 found that 82% of the respondents to the National Comorbidity Survey with lifetime GAD met criteria for significant role impairment (eg, they were separated or divorced or they were unemployed) and interference with daily activities. Massion et al.,4 examining participants in the Harvard /Brown Anxiety Disorders Research Program, found poorer role functioning, social functioning, and overall functioning among patients with GAD than among control participants.
In addition to studying role impairment, investigators have begun to examine quality of life to determine the impact of anxiety disorders. Ratings of life interference or role impairment measure the effect of the disorder on an individual's ability to perform expected role behaviors. In contrast, quality of life assessments measure dissatisfaction with life, due to the illness, from the perspective of the individual with the disorder or significant others. Persons with GAD have been found to report poorer perceptions of emotional health than have persons with panic disorder.4 Wives with GAD have been found to perceive their marriages as less satisfying than have other wives.5
Another indicator of the severity of a disorder is its duration. GAD has been found to begin most often before the age of 20, often following a chronic course.6 Between 60% and 80% of patients with GAD have reported worrying their whole life. Elderly persons often suffer from debilitating generalized anxiety, suggesting that this disorder may persist into late adulthood. Finally, spontaneous remission of symptoms during a 2-year period has been found to be low, suggesting that, if untreated, GAD will remain a consistent problem.6
GAD has been found to be prevalent in primary care medical settings and is one of the most common diagnoses among patients presenting with medically unexplained somatic complaints.7 An analysis of data from the Epidemiologic Catchment Area study found that GAD was associated with increased use of health care services.8 A recent study demonstrated that GAD is associated with significantly increased health care costs and decreased productivity levels.9
One challenge to the notion of GAD as an impairing condition is the high degree of comorbidity that is typically characteristic of the disorder. Wittchen et al.3 found that approximately 90% of individuals with GAD also met criteria for another Axis I disorder. The frequent co-occurrence of other disorders such as major depression and panic disorder was a major factor in assigning GAD a residual status in the DSM-III.
However, in their review of epidemiologic findings of GAD, Kessler et al.10 provide a strong argument that, despite high rates of comorbidity, GAD is a debilitating condition in its own right. They reviewed several studies that found that individuals with "pure" GAD (noncomorbid) had significant life impairment in multiple domains when compared with individuals without the condition. This finding suggests that the dysfunction found by the above studies is not solely due to co-occurring conditions.
Kessler also reviewed an investigation that he had conducted with colleagues in which he found that individuals with GAD without major depression did not differ in impairment from individuals with major depression without GAD. However, individuals who suffered from both conditions were more likely to be impaired than were individuals who had only one disorder. Kessler provides convincing data that GAD is often a precursor to these comorbid conditions. He found that individuals with GAD were 62 times more likely than individuals without the condition to have a major depressive episode. No other anxiety disorder showed this degree of risk for major depression (the next highest was panic disorder, with a risk ratio of 28).
Taken together, these data clearly show that GAD, even in its pure form, results in significant decrements in role functioning and quality of life, leads to increased use of health care services, and is frequently a chronic and unremitting disorder.
Misconception 2- Effective Treatment Requires the Patient to Uncover and Work Through Early Traumas
Traditional psychoanalytic theory proposes that anxiety symptoms of the sort seen in patients with GAD can be effectively treated only by uncovering memories of early trauma.11 There are some data supporting the notion that patients with GAD have experienced an excess of early trauma. Torgersen12 found that individuals with GAD were more likely to report the death of a parent prior to age 16. Borkovec13 found a significantly greater frequency of past traumatic events among individuals with GAD compared with a group without GAD. Furthermore, participants with GAD were VA times more likely to have traumas involving death, illness, or injury and 4 to 6 times more likely to have traumas involving assault or emotional events. Roemer et al.14 found that 52% of patients with GAD reported past traumatic events and that patients with GAD were more than twice as likely to have a history of trauma than were non-anxious control participants.
Although these findings do suggest that patients with GAD are more likely to have a history of trauma, there are no data from randomized, controlled trials supporting the assertion that treatment must focus on these early traumas to be effective. In fact, a randomized trial conducted by Durham et al.15 compared analytic therapy (which presumably examined early traumas) with CBT for GAD and found that CBT was superior to analytic therapy at posttreatment and follow-up.
Crits-Christoph et al.16 showed that a supportive-expressive treatment aimed at helping patients discover the effect of dangerous or traumatic experiences on their levels of worry and subsequent interpersonal difficulties was helpful to those with GAD in an open trial. However, this treatment did not exclusively focus on traumatic childhood experiences, but rather centered on any self-perceived threatening event or series of events that occurred at any point in the life cycle.
In addition, evidence from numerous randomized trials (summarized below) showing that CBT provides effective treatment for GAD indicates that effective treatment need not involve the process of uncovering and working through early traumas. Thus, we are not aware of good evidence supporting the notion that effective treatment of GAD requires uncovering and working through early traumas.
Misconception 3- CBT Produces Immediate Relief of Symptoms. But Not Long-Lasting Relief
CBT is an active, problem-solving therapy focused on teaching the patient coping strategies to alleviate symptoms and distress. Although the cognitive-behavioral protocols developed17,18 for treating GAD differ somewhat, they have several features in common and we describe them briefly here.
Cognitive-behavioral protocols for treating GAD typically have several components. Selfmonitoring is often a central aspect of treatment. The cognitive-behavioral therapist often begins treatment by asking the patient to monitor the onset and offset of bouts of worry. Sometimes the patient with GAD will insist that this is impossible because he or she worries all the time. However, the patient's perception that he or she worries all the time is usually not accurate, and monitoring will reveal this. Moreover, until patients develop the ability to notice when worry begins, they will not be able to use the onset of worry as a cue to initiate coping strategies.
Cognitive-behavioral therapists also teach patients to use relaxation strategies to counter their chronic physiological arousal. Cognitive restructuring is used to teach patients to identify and correct cognitive distortions, such as the tendency to overestimate the probability of catastrophic events. Patients also learn problem-solving strategies, as worriers often confuse worry with problem solving. They learn how "worry behaviors" (behaviors driven by fear cognitions) feed fears rather than alleviate them. Patients learn to postpone, reduce, or eliminate worry behaviors. They learn to fully expose themselves to fearful thoughts and images, instead of jumping quickly from one fear to another without completely processing any fear, which is their usual strategy.
Imaginai exposure strategies are used to promote emotional processing. In imaginai exposure, patients are asked to imagine their worst fear and to exaggerate and keep thinking about it for at least 20 minutes before they use cognitive restructuring and other coping strategies to manage it. Exposure interventions are based on the notion that the worry behavior of GAD is, at least in part, an avoidance maneuver that allows patients to avoid complete processing of fearful thoughts and images.
Initial results of randomized, controlled trials examining the outcome of CBT for GAD are promising. Recent meta-analyses by Gould et al.,19 Borkovec and Whisman,20 and Chambless and Gillis21 indicate that CBT for GAD, when studied in randomized, controlled trials, consistently shows outcomes that are superior to patients in a wait-list control condition. In a recent study,22 CBT was superior to nondirective psychotherapy.
Clinicians who are new to the cognitivebehavioral conceptualization and interventions for GAD are often concerned that CBT will provide short-term therapy that leaves patients vulnerable to relapse or to symptom substitution when "deeper" problems, not treated by CBT, reemerge. Certainly these concerns make eminent theoretical sense for clinicians who were taught that GAD arises due to repressed fears resulting from early childhood traumas that must be worked through to get relief. However, the conceptualizations of GAD developed by cognitive-behavioral theorists, which include the view of worry as avoidance of complete emotional processing of feared material, do not lead to predictions of relapse or symptom substitution when patients learn active cognitive and behavioral coping strategies. In part, this is because, as part of CBT, patients learn to more fully process, rather than to avoid, fearful thoughts. In addition, they learn to resume using active coping strategies whenever symptoms reemerge.
Contrary to the symptom substitution and relapse hypotheses, research suggests that patients treated with CBT often remain asymptomatic long after treatment ends. In a meta-analysis, Gould et al.19 reviewed 6 randomized, controlled trials of CBT and found that patients treated with CBT for GAD reliably maintained their gains during a follow-up interval of at least 6 months. In a review of 11 randomized, controlled trials, Borkovec and Whisman20 concluded that follow-up assessment of cognitive-behavioral treatments (typically 6 to 12 months posttreatment) consistently showed that patients typically maintained their gains and sometimes showed that they made even further improvements in their condition.
Thus, patients treated with CBT appear to show good maintenance of gains acquired during the acute treatment. Relapse is not a significant problem for those who respond to CBT. As Borkovec and Whisman20 pointed out, the most significant problem in the psychosocial treatment of GAD currently is that treatments are not sufficiently powerful. To date, randomized, controlled trials have suggested that only 50% to 60% of patients who receive CBT for GAD can expect to be free of anxiety at the end of treatment.20 Several investigators in the United States (including Thomas Borkovec at Pennsylvania State University, David Barlow at Boston University, and Richard Heimberg at Temple University) are actively working to develop new protocols for the treatment of GAD. For example, Newman, Castonguay, and Borkovec are conducting a randomized, controlled trial comparing a new treatment that combines interpersonal, humanistic, and CBT interventions with a more traditional CBT.
Misconception 4 - Long-Term Treatment With Benzodiazepines Is a Benign Therapeutic Strategy
Benzodiazepines are widely used to treat GAD,23 and there are data supporting the efficacy of long-term therapy with benzodiazepines for GAD, although this is controversial.24 The benefits of the long-term treatment of GAD with benzodiazepines are offset by several significant drawbacks and risks, as described below.
First, although anxiety may be well controlled during treatment with benzodiazepines, the return of symptoms is common when medication is discontinued. Rickels et al.25 reported a relapse rate of 81% among patients treated for 4 weeks with a benzodiazepine for "anxiety neurosis."
Second, many patients find it difficult or impossible to stop using benzodiazepines.26 Schweizer et al.27 reported that 32% to 42% of patients who had received long-term treatment with benzodiazepines and were attempting to discontinue them were unable to remain drugfree during the 5-week period of study. Ninety percent of these patients experienced a physical withdrawal reaction, although usually the severity of these symptoms was rated as mild to moderate. Current guidelines suggest that it is generally inappropriate to prescribe benzodiazepines for any patient with a history of significant substance abuse, and there is some evidence to support this practice.28,29
Finally, the mechanism of action of the benzodiazepines, if used in combination with psychosocial treatments, may conflict with, and thus undermine, the mechanisms of action of psychosocial treatments, especially CBT. Benzodiazepines and CBT may conflict in several ways.28 Evidence that learning and retention can be drug-state dependent raises the possibility that benzodiazepines may interfere with the learning of coping strategies. In addition, the presence of benzodiazepines may disrupt the process of habituation that is presumed to underlie the benefits of exposure therapy. The fact that benzodiazepines reduce or eliminate anxiety may make it difficult for patients to learn and practice strategies for coping with anxiety in treatment and may decrease patients' motivation to learn to manage anxiety.30 In fact, the use of benzodiazepines may be conceived of as an avoidance strategy, and as such may promote the use of other avoidance strategies that are generally viewed by therapists as part of the maladaptive coping style of the patient with GAD.
In view of these drawbacks of therapy with benzodiazepines, we encourage clinicians to consider pharmacotherapies for GAD that do not employ benzodiazepines. Two medications currently have Food and Drug Administration approval for the treatment of GAD: buspirone and venlafaxine.
The efficacy of buspirone in treating DSM-HI GAD, with its 1-month duration of symptoms, has been well established, but there is little evidence of its efficacy in treating DSM-IV GAD, which requires a 6-month duration of symptoms.30 The effectiveness of buspirone may also be limited by the fact that if a patient has experienced the immediate relief offered by a benzodiazepine, he or she may be unwilling to wait several weeks for buspirone to take effect.31 Problems with withdrawal are minimal compared with the benzodiazepines, and patients treated with buspirone may have a lower rate of symptom recurrence than those treated with benzodiazepines.32 There is evidence that buspirone may be effective for comorbid depressive symptoms as well.33
Venlafaxine is the most widely studied antidepressant for the treatment of GAD. It has been shown to be effective, well tolerated, and safe in this population.34
Trazodone and the tricyclic antidepressants doxepin, Imipramine, and domipramine have been well studied and shown to be efficacious for GAD, but are accompanied by a variety of anticholinergic, antiadrenergic, antihistamine or other side effects.35 Newer serotonergic agents such as nefazodone, mirtazapine, and the selective serotonin reuptake inhibitors are also effective for GAD, with the advantage of being more easily tolerated.36 The side effects and withdrawal reactions associated with these drugs are much less problematic than those associated with the benzodiazepines. In addition, the antidepressant treatment of GAD has the added benefit of treating a wide variety of comorbid mood, anxiety, and behavioral symptoms and illnesses. It remains to be determined whether antidepressants, such as the benzodiazepines, provide benefits only during treatment, with patients vulnerable to relapse when medication is stopped.
Currently available medications thus present the pharmacotherapist with a variety of options for treating GAD that do not expose patients to the risks posed by the benzodiazepines. New pharmacologic agents for the treatment of GAD may become available soon, including the partial benzodiazepine agonists abecarnil and bretazenil.37
We have reviewed four common misconceptions about the treatment of GAD. We have evaluated these beliefs about GAD and its treatment by examining the results of empirical studies of GAD, including randomized, controlled trials examining the outcomes of treatment of GAD. We believe that the available data yield the following conclusions about GAD and its treatment:
* GAD often causes significant distress and impairment and therefore merits clinical attention and aggressive treatment.
* The psychosocial treatments with the greatest support from data from randomized, controlled trials are cognitive-behavioral treatments, which consist of interventions designed to help patients reduce the physiological arousal and the cognitive distortions that are at the heart of the disorder.
* There is no evidence from randomized, controlled trials that the uncovering of early childhood traumas is necessary to recover from GAD.
* Follow-up data indicate that gains from short-term CBT are maintained during the longterm.
* Response rates in the cognitive-behavioral treatments are typically 50% to 60%, indicating the need for the development of more powerful interventions. Some new interventions currently being evaluated combine CBT with emotionfocused and interpersonal approaches.
* Benzodiazepines provide rapid and effective relief of symptoms, but expose patients to the risk of relapse, withdrawal symptoms, and discontinuation difficulties and may interfere with simultaneous psychosocial interventions. Other pharmacologic agents, particularly buspirone and the antidepressants, expose patients to fewer of these risks and merit consideration in the treatment of GAD.
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