231 Generalized Anxiety Disorder

DSM-IV-TR Criteria

• A. Excessive anxiety and worry (apprehensive expectation), occurring more days for at least six months about a number of events or activities (such as work or school performance).
• B. The person finds it difficult to control their worry.
• C. An unrealistic fear or worry, especially in new or unfamiliar situations.
• D. The anxiety and worry are associated with three or more of the following six symptoms (with at least some symptoms present for more days for at least the past six months). NOTE: Only one item is required in children:
  1. Restlessness or feeling keyed up or on edge
  2. Being easily fatigued
  3. Difficulty concentrating or mind going blank
  4. Irritability
  5. Muscle tension
  6. Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
• E. The focus of the anxiety and worry is not confined to features of an Axis I disorder, e.g., the anxiety or worry is not about having a panic attack (as in panic disorder), being embarrassed in public (as in social phobia), being contaminated (as in obsessive-compulsive disorder), being away from home or close relatives (as in separation anxiety disorder), gaining weight (as in anorexia nervosa), having multiple physical complaints (as in somatization disorder), or having a serious illness (as in hypochondriasis), and the anxiety and worry do not occur exclusively during post-traumatic stress disorder.
• F. The anxiety, worry, and physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
• G. The disturbance is not due to the direct psychological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism) and does not occur exclusively during a mood disorder, a psychotic disorder, or a pervasive developmental disorder.

Associated Features

In addition to the diagnostic features above, people with GAD often report several other types of psychological and physiological symptoms. These can include trembling (particularly of the extremities), nervous twitching, feeling shaky, and muscle soreness (usually related to high levels of tension they are experiencing). They can also experience somatic symptoms such as sweating, hot flashes, nausea, diarrhea, or an exaggerated startle response. Symptoms of autonomic hyperarousal, like rapid heart rate, shortness of breath, and dizziness are not as common as in other anxiety disorders, such as panic disorder and post-traumatic stress disorder, but can be seen.

Comorbidity of other disorders and GAD is extraordinarily high, with epidemiological studies showing rates of 90% in the general population, and clinic studies showing rates between 45-98%. Major depressive disorder (MDD) is the single most common comorbid disorder, with some 60% of patients meeting diagnostic criteria for both. Other typical comorbids include the other anxiety disorders, sleep disorders, and chronic pain. These high rates of comorbidity have lead some to question if GAD should actually be classified as its own, separate disorder or if it is instead a prodrome (that is, a precursor to) or symptom of other disorders. It appears, based on current research, that it is properly classified as its own disorder for three primary reasons: it can be both reliably and validly diagnosed; non-comorbid GAD can be seen; and the high comorbidity rates may be an artifact of the DSM diagnostic criteria.

The impact of GAD on an individual can be devastating. Compared to the other anxiety disorders, individuals with GAD tend to show higher levels of social and occupational impairments. In terms of quality of life, GAD patients show decreases that are comparable to those with physical illness such as diabetes, hypertension, and congestive heart failure. Persons with GAD also tend to have much higher numbers of visits, and costs of visits, to physicians annually than do people without anxiety. In fact, over half of patients diagnosed with irritable bowel syndrome (IBS) have comorbid GAD diagnoses, and many of them are not aware of this.

Child vs. Adult Presentation

In children and adolescents, the anxieties and worries seen in GAD are often focused on their performance at school or in sporting events – situations when their performance is being evaluated or observed by others. There may also be a large concern about being punctual in social situations. Children with GAD may also show signs of being overly conforming, showing perfectionism, and being unsure of themselves. They may tend to redo tasks because they are dissatisfied with whatever they are trying to accomplish, which is generally an idea that realistically they cannot achieve, while constantly checking and changing things. Retrospectively, many diagnosed with GAD as adults report having felt anxious all their lives, and over half of those who present for treatment report onset in childhood or adolescence. Onset after 20 years old is not uncommon, though. The course of GAD has traditionally been considered to be chronic, but recent research shows that under 80% of those with lifetime diagnosis do not have chronic, clinical levels of worry.

Gender and Cultural Differences in Presentation

The diagnosed prevalence rate of GAD in females is over double that of males. Lifetime prevalence ratios are 1 male to every 1.9 females, with 12-month ratios of 1:2.2. There are different patterns of comorbidity seen between genders as well, with higher rates of substance use disorders (particularly alcohol use) and antisocial personality disorders seen in males. Females, in contrast, show higher numbers of comorbid anxiety and mood disorders. Interestingly, even when controlling for comorbid problems, females also show higher rates of disability than males. The group at highest risk for having GAD are females who are middle-aged, not married, and of low income.

Culturally, persons living in the U.S. who are of Asian, Hispanic, or African descent are at lower risk for having GAD than Caucasians. Some studies have shown that those of minority status in the U.S., as well as persons living in Eastern Asia, experience more of the somatic symptoms of GAD and report fewer psychological or worry symptoms. There is some research, however, that shows psychological symptoms are as present in Chinese and Vietnamese people, but that they must be specifically asked about, as these populations are more likely to concentrate on somatic complaints.

Epidemiology

GAD prevalence rates are quite high across a number of studies. The Epidemiological Catchment Area Study reported that the lifetime prevalence rates range from 4.1% to 6.6% for DSM-III criteria. The National Comorbidity Survey Replication, which examined DSM-IV criteria in the United States, reported a lifetime prevalence rate of 5.7%, with 12-month rates of 2.7%. Very similar rates are reported in European samples, with rates between 1.2-1.9% for current and 4.3-5.9% for lifetime prevalence.

Etiology

It is not entirely known what causes generalized anxiety disorder, but a number of factors likely contribute. Evolutionarily, anxiety is highly useful, as it prepares the body for “fight or flight” by activating the sympathetic nervous system. In GAD, like in other anxiety disorders, this activation appears to be in response to what should be non-anxiety provoking stimuli. In other words, people with GAD display a specific cognitive bias that causes them to attend heavily to potentially threatening stimuli, as well as interpret ambiguous stimuli as if it were threatening.

While GAD does not necessarily run in families, that does not mean there is not a role that genetics play in the disorder. Instead of a propensity toward GAD, children instead inherit a greater likelihood of expressing high levels of neuroticism and anxiety sensitivity. Indeed, genetic studies show that there is a high genetic overlap between GAD and major depression. The environment may be responsible for how this vulnerability is then expressed. Intriguingly, one environmental risk factor may be smoking cigarettes, as teenagers who smoke are 5-6 times as likely to develop GAD as non-smokers. Trauma and stressful events like abuse, death of a family member, divorce, or changing careers may also lead to development of GAD.

At the level of the brain, several neurotransmitters have been found to be linked to GAD (as well as a number of other disorders). Serotonin and norephinephrine have both been implicated, with the causal mechanism seeming to be a lack of receptor sensitivity to them. The amygdale is also disrupted in GAD, impacting the appropriate rely of sensory information to the rest of the brain. This may help to explain the threat-bias displayed by those with GAD.

Psychologically, the central and defining feature of GAD is worry (leading some to propose it actually be renamed “Generalized Worry Disorder). Where the typical, non-clinically anxious person spends approximately 15% of their day worrying, people with GAD may spend as much as 60% engaged in worry. For them, worry is an avoidant coping strategy which is maintained by two types of reinforcement. First, worry leads to decreased physiological and emotional reactivity in response to stressors, which means it is positively reinforcing. Second, it is also negatively reinforced, as the vast majority of worries and fears do not come true; people with GAD attribute these bad things as not happening because they worried about them. This not only maintains worry, but causes people to see it as a good, beneficial activity. Unfortunately, it also has negative consequences, particularly increasing the frequency of intrusive, anxiety-provoking mental imagery, which results in a sense of uncontrollability. This in turn makes the individual with GAD both more likely to worry and increasingly impaired by their worry. As for why people might worry more often in the first place, it appears to be due to a high degree of intolerance for uncertainty. Uncertain or ambiguous situations are often viewed as stressful and upsetting, unfair, negative, avoided at all costs, and interfering with one’s ability to function. These negative association with uncertainty then cause people to begin worrying about encountering them in the future.

Empirically Supported Treatments

Treatment for GAD can be done both via psychotherapy and pharmacology. There are similar effect sizes seen for cognitive-behavioral therapies (0.7) and medications (0.6). Unfortunately, though, the majority of persons with GAD lack access to properly trained CBT clinicians, and other therapies (supportive, psychodynamic, humanistic) are just not effective. This leads to the majority of persons with GAD being treated with medication, which is actually less cost-effective and shows fewer long-term benefits than CBT.

In terms of medication, two primary classes of drugs are used: benzodiazepines (BZD) and antidepressants (AD). With BZD, such as alprazolam, bromazepam, lorazepam, and diazepam, are quite effective at relieving GAD in the short-term, but are discouraged for long-term use. This limitation is recommended due to potential for developing tolerance and subsequent abuse, as within 4-6 weeks of use they are generally no more effective than a placebo. The most common side effects of BZD are dizziness, drowsiness, decreased alertness, and poor concentration. The most commonly prescribed drugs for GAD are types of AD, such as fluoxetine, duloxetine, escitalopram, paroxetine, and sertraline. There is little evidence to suggest an enormous difference in efficacy between tricyclics (TCA), serotonin reuptake inhibitors (SRI), or combined serotonin-norepinephrine reuptake inhibitors (SNRI). While these take considerably longer to show a response, sometimes up to six weeks after beginning taking them for full effectiveness, they have little risk of addiction and can be discontinued relatively easily using a gradually stepped-down dosage. Side effects often seen vary depending on the specific drug, with TCA often having more severe profiles. Common TCA side effects include sedation, dry mouth, postural hypotension, while common SRI side effects are dizziness, nausea, disturbed appetite, and sexual dysfunction.

Psychotherapeutically, CBT vastly outperforms other therapeutic modalities, at both immediate post-treatment and long-term follow-up. There is a very low (under 10%) rate of dropouts in CBT. Interestingly, shorter dosages (8-10 sessions) have been shown to be equally effective as longer ones, with treatment gains seen up to two years after treatment has been discontinued. This makes CBT superior to medication in relapse prevention, as well as more cost effective. It is important to note, however, that although there are large effect sizes, especially compared to wait-list controls (1.09), that only about half of patients will have their worry drop to non-clinical levels. There are four traditional components to CBT for GAD: self-monitoring, applied relaxation training, cognitive therapy, and the rehearsal of relaxation and cognitive restructuring in the real world.

Self-monitoring teaches patients to objectively observe their anxious responses and note the triggers of worry. This is crucial because the earlier a patient can identify worry, the more effective the deployment of coping responses will be. In the relaxation training, patients are taught progressive muscle relaxation in session, then are required to practice it twice daily until they have mastered the ability to, on conscious demand, release muscle tension from their entire body. Once this mastery is obtained, they will then rehearse this skill in real-life situations. Cognitive therapy is used to help correct the negative, pervasive cognitive biases seen in GAD. This is done by 1) identifying how the patient is thinking and the beliefs about self, world, and future that underlie those thoughts, 2) evaluating the accuracy of those cognitions through examination of their logic, probability, and past evidence, 3) generating alternative, more accurate interpretations, predictions, and ways of believing, and 4) using these new perspectives whenever worry is detected and engaging in deliberate behavioral experiments to test if the worry is accurate or not. After relaxation and cognitive therapy are taught, the therapist will have the patient practice using these coping strategies in session by eliciting worry. In GAD, it is key to use intense imagery, not just verbal descriptions, to induce higher anxiety levels, as talking it out is analogous to worrying aloud, which suppresses the intensity of emotional reactivity.

Proposed DSM-5 Revisions

The proposed changes in GAD criteria for DSM-5 primarily reflect an increase and focus on worry as the defining factor of the disorder. By drawing more attention to this key aspect of GAD, and putting less emphasis on physiological symptoms, it is hoped that the diagnostic criteria will become more reliable and better able to differentiate from other anxiety disorders. Other major changes include the decrease of duration of worry from 6 to 3 months, and the number of symptoms aside from worry decreased from 3 to 1. While the duration decrease will likely increase the number of people who qualify for this diagnosis, the symptom drops have not been shown to do the same in research trials. Finally, adding an avoidance criteria to the diagnosis brings the criteria more in line with the other anxiety disorders and is supported by both research data and clinical opinion.

Key References

Andrews, G., Hobbs, M.J., Borkovec, T.D., Beesdo, K., Craske, M.G. et al. (2010). Generalized Worry Disorder: A review of DSM‐IV Generalized Anxiety Disorder and options for DSM‐V. Depression and Anxiety, 27, 134‐147.

Baldwin, D., Woods, R., Lawson, R., & Taylor, D. (2011). Efficacy of drug treatments for generalised anxiety disorder: Systematic review and meta‐analysis. BMJ: British Medical Journal, 342. Prepublication copy.

Newman, M. G., & Borkovec, T. D. (2002). Cognitive behavioral therapy for worry and generalized anxiety disorder. In G. Simos (Ed.), Cognitive behaviour therapy: A guide for the practising clinician (pp. 150–172). New York, NY: Taylor & Francis.

van der Heiden, C., Methorst, G., Muris, P. and van der Molen, H. T. (2011). Generalized anxiety disorder: clinical presentation, diagnostic features, and guidelines for clinical practice. Journal of Clinical Psychology, 67, 58–73.