Anxiety, Generalized Anxiety Disorder (GAD)


Article Author:
William Gossman
Sadaf Munir


Article Editor:
Veronica Takov


Editors In Chief:
Laurie Graham
Andrew Wilt
Mary Cataletto


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/11/2019 11:50:55 PM

Introduction

Generalized anxiety disorder is one of the most common mental disorders. Up to 20% of adults are affected by anxiety disorders each year. Generalized anxiety disorder produces fear, worry, and a constant feeling of being overwhelmed. Generalized anxiety disorder is characterized by persistent, excessive, and unrealistic worry about everyday things. This worry could be multifocal such as finance, family, health, and the future. It is excessive, difficult to control, and is often accompanied by many non-specific psychological and physical symptoms. Excessive worry is the central feature of generalized anxiety disorder.[1][2][3]

Diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, fifth  edition (DSM-V) include the following:

  • Excessive anxiety and worry for at least six months
  • Difficulty controlling the worrying.
  • The anxiety is associated with three or more of the below symptoms for at least 6 months:
  1. Restlessness, feeling keyed up or on edge
  2. Being easily fatigued
  3. Difficulty in concentrating or mind going blank, irritability
  4. Muscle tension
  5. Sleep disturbance
  6. Irritability
  • The anxiety results in significant distress or impairment in social and occupational areas
  • The anxiety is not attributable to any physical cause

Etiology

The etiology may include:

  • Stress
  • Physical condition such as diabetes or other comorbidities such as depression
  • Genetic, first-degree relatives with generalized anxiety disorder (25%)
  • Environmental factors, such as child abuse
  • Substance abuse.

Epidemiology

Childhood anxiety occurs in about 1 in 4 children at some time between the ages of 13 and 18 years. The median age at onset is 11 years.  However, the lifetime prevalence of a severe anxiety disorder in children ages 13 to 18 is approximately 6%. General prevalence in children younger than 18 years is between 5.7% and 12.8%. The prevalence is approximately twice as high among women as among men.[4][5][6]

The American Psychiatric Association first introduced the diagnosis of generalized anxiety disorder two decades ago in the DSM-III. Before that time, generalized anxiety disorder was conceptualized as one of the two core components of anxiety neurosis, the other being panic. A recognition that generalized anxiety disorder and panic, although often occurring together, are sufficiently distinct to be considered independent disorders led to their separation in the DSM-III.

The DSM-III definition of generalized anxiety disorder required uncontrollable and diffuse (i.e., not focused on a single major life problem) anxiety or worry that is excessive or unrealistic in relation to objective life circumstances, and that persists for one month or longer. Several related psychophysiological symptoms were also required for a diagnosis of generalized anxiety disorder. Early clinical studies evaluating DSM-III according to this definition found that the disorder seldom occurred in the absence of another comorbid anxiety or mood disorder. Comorbidity of generalized anxiety disorder and major depression was especially strong and led some commentators to suggest that generalized anxiety disorder might better be conceptualized as a prodrome, residual, or severity marker than as an independent disorder. The rate of comorbidity of generalized anxiety disorder with other disorders decreases as the duration of generalized anxiety disorder increases. Based on this finding, the DSM-III-R committee on generalized anxiety disorder recommended that the duration required for the disorder be increased to six months. This change was implemented in the final version of the DSM-III-R. Additional changes in the definition of excessive worry and the required number of associated psychophysiological symptoms were made in the DSM-IV.

These changes in diagnostic criteria led to delays in cumulating data on the epidemiology of generalized anxiety disorder. Nonetheless, such data became available over the past decade. As described in more detail later, this new data challenged the view that generalized anxiety disorder should be conceptualized as a prodrome, residual, or severity marker of other disorders. Instead, it suggest that generalized anxiety disorder is a common disorder that, although often comorbid with other mental disorders, does not have a rate of comorbidity that is higher than those found in most other anxiety or mood disorders. The new data also challenged the validity of the threshold decisions embodied in the DSM-V.

Pathophysiology

The exact mechanism is not entirely known. Anxiety can be a normal phenomenon in children. Stranger anxiety begins at seven to nine months of life.  Noradrenergic, serotonergic, and other neurotransmitter systems are believed to play a role in the body's response to stress. The serotonin system and the noradrenergic systems are common pathways involved in anxiety. Many believe that low serotonin system activity and elevated noradrenergic system activity are responsible for its development. It is, therefore, selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) that are the first-line agent for its treatment. 

History and Physical

Patients with anxiety can pose a diagnostic challenge, as somatic symptoms are more common than psychologic symptoms. Most patients present with vague or nonspecific somatic complaints, including, but not limited to, shortness of breath, palpitations, fatigability, headache, dizziness, and restlessness.  Patients may also describe psychologic symptoms such as excessive, nonspecific anxiety and worry, emotional lability, difficulty concentrating, and insomnia.

Factors commonly associated with generalized anxiety include:

  • Female gender
  • Unmarried
  • Poor health
  • Low education
  • Presence of stressors

The median age of presentation is 30 years

Many scales have been developed to assess the severity and diagnosis. The GAD-7 has been validated as a diagnostic tool and severity assessment scale.

Evaluation

Initial assessment begins by addressing behavior or somatic symptoms. Evaluate for psychosocial stress, psychosocial difficulties, and developmental issues. Review past medical history, including trauma, psychiatric conditions, and substance abuse.[7]

The following evaluation may be obtained to exclude organic causes:

  • Thyroid function tests
  • Blood glucose level 
  • Echocardiography
  • Toxicology screen

The Generalized Anxiety Disorder 7-Item (GAD-7) Questionnaire is a screening tool that can also be used to monitor patients with generalized anxiety disorder.

Treatment / Management

The two main treatments for generalized anxiety disorder are cognitive behavior therapy and medications. Patients may benefit most from a combination of the two. It may take some trial and error to discover which treatments work best.[8][9][10]

Cognitive Behavioral Therapy

This includes psychoeducation, changing maladaptive thoughts patterns, and gradual exposure to anxiety-provoking situations.

Pharmacotherapy

Several types of medications are used to treat generalized anxiety disorder.

Antidepressants

Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) classes are the first-line agents with a response rate of 30% to 50%. This class of drugs includes escitalopram (Lexapro), duloxetine (Cymbalta), venlafaxine (Effexor XR) and paroxetine (Paxil, Pexeva). In a study, 81% of children with anxiety disorders who received combined sertraline hydrochloride and CBT were responded to the treatment.

Antipsychotics may also help some patients, especially those with associated behavior problems.

Benzodiazepines

Examples diazepam and clonazepam are long-acting agents. These agents are used when an immediate reduction of symptoms is desired, or a short-term treatment is needed. Generally, cooperative and compliant patients who are aware that their symptoms have a psychological basis are more likely to respond to benzodiazepines. Since there is a concern for misuse and dependence, patients with a history of alcoholism or drug abuse are not appropriate candidates for this treatment.

Buspirone (BuSpar)

Buspirone is a non-benzodiazepine which does not cause dependency. It is also less sedating than benzodiazepines, and tolerance does not occur at therapeutic doses. This agent has a therapeutic lag in the efficacy of two to three weeks which limits its use.

All medications should be titrated slowly and continued for at least 4 weeks to determine if they work. Once symptoms are under control, the medications need to be used for at least 12 months before gradually tapering them. Every single medication has adverse effects like weight gain, hyperlipidemia, and diabetes; thus the patients need to be monitored.

Psychotherapy is used in addition to medications; this combination has proven to be effective.

Education of the patient is vital as it can help ease anxiety. The triggers for anxiety should be managed like avoiding caffeine, alcohol, nicotine, stress) and improving sleep.

Many complementary and alternative remedies are available but the evidence to support their efficacy is lacking. Further, some agents like Kava may injure the liver. Others like St John;s wort and hydroxytryptophan may interact with SSRIs and induce the serotonin syndrome.

Differential Diagnosis

  • Hyperthyroidism
  • Pheochromocytoma
  • COPD
  • TIA
  • Epilepsy
  • Bipolar disorder
  • Use of caffeine, decongestants, albuterol

Prognosis

The prognosis for patients with generalized anxiety disorder is guarded. Many patients are not compliant with medications because of cost and adverse effects. Relapses are common and patients often search physicians who comply with their needs. Because of the lack of conventional medicine to cure the disorder, many opt for alternative therapies without much success. Overall, the quality of life of these patients is poor.

Pearls and Other Issues

Consider further evaluation for anxiety disorder if an adult is excessively anxious or an infant or child is excessively clingy and difficult to console during the pediatric visit. Many medical conditions may mimic anxiety disorders. One should distinguish between the anxiety and the illness and should evaluate for organic diseases before making this diagnosis.

Enhancing Healthcare Team Outcomes

Anxiety disorders are very common and can have diverse presentation of signs and symptoms. The condition has a very high morbidity and mortality and thus is best managed by an interprofessional team that includes a mental health nurse, pharmacist, psychologist, a psychiatrist and the primary care provider. Many patients have moderate to severe symptoms and lead a poor quality of life. Most have no idea that the condition can be treated. Thus, the key to improving outcomes is patient education. The nurse practitioner, pharmacist and primary care provider should urge the patient to stop tobacco, alcohol and caffeinated beverages. In addition, relief of stress is vital and thus a referral for cognitive behavior therapy may help.

There are many drugs that can be used to treat anxiety but they all have side effects, which is a common reason for non-compliance. The pharmacist should emphasize the benefits of these medications and urge compliance to improve the symptoms. At the same time, the primary care provider should monitor for hyperlipidemia, diabetes and weight gain as a result of the medications.

Overall, anxiety disorders are underdiagnosed and undertreated. When left untreated, anxiety disorders often lead to severe depression and abuse of drugs and alcohol. In addition, there is a high rate of suicide among these patients. Many patients with chronic anxiety have a poor quality of life. The education of both the patient and family is important to reduce the high morbidity. Family members should help ensure medication compliance and provide a supportive environment. Unfortunately, despite optimal treatment, relapse rates are high. [11][12][13](Level V)

 


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Anxiety, Generalized Anxiety Disorder (GAD) - Questions

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Which of the following statements about co-existing anxiety disorders in women who have drug addiction is FALSE?



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A 31 year old female presents with a long history of headaches occurring 1 or 2 times a week that are typical for tension-type headaches (TTH). The patient has seen several physicians and had a normal MRI last year. She asks many questions and is concerned that there may be a more serious cause. Preventive medication is offered but she is concerned about possible side effects. She leaves without a prescription but calls numerous times in the next couple of weeks. Which of the following medications would be most appropriate?



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Which age group has the highest prevalence of generalized anxiety disorder?



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Which of the following drugs is least effective in the treatment of generalized anxiety disorder?



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What is not a diagnostic criterion for generalized anxiety disorder?



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Anxiety, Generalized Anxiety Disorder (GAD) - References

References

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Latas M,Trajković G,Bonevski D,Naumovska A,Vučinić Latas D,Bukumirić Z,Starčević V, Psychiatrists' treatment preferences for generalized anxiety disorder. Human psychopharmacology. 2018 Jan     [PubMed]
Driot D,Bismuth M,Maurel A,Soulie-Albouy J,Birebent J,Oustric S,Dupouy J, Management of first depression or generalized anxiety disorder episode in adults in primary care: A systematic metareview. Presse medicale (Paris, France : 1983). 2017 Dec     [PubMed]
Roberge P,Normand-Lauzière F,Raymond I,Luc M,Tanguay-Bernard MM,Duhoux A,Bocti C,Fournier L, Generalized anxiety disorder in primary care: mental health services use and treatment adequacy. BMC family practice. 2015 Oct 22     [PubMed]
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Dold M,Bartova L,Souery D,Mendlewicz J,Serretti A,Porcelli S,Zohar J,Montgomery S,Kasper S, Clinical characteristics and treatment outcomes of patients with major depressive disorder and comorbid anxiety disorders - results from a European multicenter study. Journal of psychiatric research. 2017 Aug     [PubMed]
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