Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Among the risk factors are family history, other mental health disorders, chronic physical illness, and a history of abuse or trauma. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Diagnosis is clinical but if history suggests an underlying disease, laboratory tests are obtained. Treatment includes a combination of psychotherapy (e.g., CBT) and medications such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

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Overview

Definition

Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months.

  • Anxiety is a normal emotional state marked by intense, frequent, irrational, and unpleasant physical and mental arousal.
  • Anxiety is a response to an unknown threat, while fear is a response to a known threat.

Epidemiology

  • Lifetime prevalence of GAD in the United States: 5.1%–11.9 %.
  • More common in women than in men (2:1)
  • Although onset is in late adolescence/early adulthood, those with GAD usually receive diagnosis and treatment later in life.

Pathophysiology

Risk factors

  • General:
    • Female 
    • Family history
    • Comorbid mental health disorders
    • Other chronic physical disorders (arthritis, GI disorders)
    • History of abuse/trauma
  • Late-onset GAD risk factors:
    • Poverty
    • Recent adverse events
    • Parental loss or separation
  • GAD is the most likely condition to coexist with another psychiatric disorder:
    • Other anxiety disorders such as phobias or panic disorder 
    • PTSD 
    • Depressive disorders 
    • Substance abuse

Pathogenesis

  • Exact etiology is still unknown. 
  • Biologic:
    • Genetic factors predispose individuals to GAD.
    • Abnormalities in neurotransmitters:
      •  Decrease in serotonin and GABA
      •  Increase in norepinephrine
    • ↑ Glucose metabolism in the cortex, limbic system, and basal ganglia 
  • Stress and traumatic events

Clinical Presentation and Diagnosis

Clinical features

  • Main hallmark is excessive worry and anxiety about different subjects accompanied by restlessness or physical tension for more than 6 months. 
  • Patients often present with various somatic symptoms; a specific nonpsychiatric diagnosis is rarely found.
  • Components:
    • Cognition:
      • Overestimating the danger
      • Poor coping skills
    • Behaviors:
      • Avoidance
      • Being distracted
      • Seeking reassurance
    • Symptoms or complaints:
      • Muscle aches (e.g., neck, back, shoulder pains)
      • Poor sleep
      • Fatigue (feeling physically and emotionally drained)
      • Restlessness (trouble relaxing)
      • Poor concentration (mind going blank)
      • Irritability or being easily annoyed
  • Course: chronic, fluctuating, and with gradual onset
  • Exclusion of substance use or other medical conditions (e.g., hyperthyroidism) and other mental disorders

Assessment

  • Workup if there are physical signs and symptoms suggestive of an underlying disease:
    • CBC
    • Thyroid function tests
    • Chemistry panel
    • ECG
    • Toxicology
  • Screening tools:
    • GAD 7-item scale: for screening and monitoring symptom severity 
    • Hospital Anxiety and Depression Scale (HADS): widely used for assessment and monitoring of anxiety and depression severity

Management

The gold standard for management of GAD is a combination of psychotherapy and pharmacotherapy.

Psychotherapy

  • CBT has the most evidence for efficacy in treating GAD. 
  • Psychodynamic therapy may uncover sources or issues linked to the patient’s anxiety. 
  • Supportive psychotherapy offers reassurance and comfort.

Nonmedical interventions

  • Exercise 
  • Diet modifications such as limiting caffeine intake

Medications

  • Medication is selected based on availability, patient tolerance to side effects, other comorbidities, and treatment history.
  • Antidepressants (selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs)) are the 1st-line treatment.
    • Highest amount of evidence for efficacy 
    • Little risk of abuse
    • SSRIs: e.g., sertraline, citalopram, and paroxetine 
    • SNRIs: e.g., venlafaxine and duloxetine
  • 2nd line: 
    • Benzodiazepines (BZD):
      • Usually avoided due to high risk of misuse
      • If used, administer only on an as-needed basis for a short period of time.
      • Those with longer duration of action (clonazepam or diazepam) are preferred. 
    • Buspirone: slow action and weaker anxiolytic effect than benzodiazepines 
    • Pregabalin: has shown some efficacy (used in Europe)
    • Tricyclic antidepressants (TCAs): less acceptable tolerability and can cause arrhythmias
    • Hydroxyzine: short-term or immediate control of symptoms

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Comparison with Other Anxiety Disorders

Table: Comparison of anxiety disorders
ConditionMost important featuresDurationTreatment
Generalized anxiety disorderChronic multiple worries, usually about issues, events, or activities≥ 6 monthsCombination of antidepressants (SSRIs) and CBT
Panic disorderRecurrent and unexpected abrupt surges (within minutes) of intense fear or discomfort≥ 1 month
  • Acute attack: BZD
  • Maintenance: SSRIs, CBT
Specific phobiaUnreasonable fear of a certain object or situations≥ 6 months
  • 1st line: CBT
  • Medication has an insignificant role.
Social phobia (social anxiety disorder)Fear or avoidance of social interactions due to concerns about being embarrassed≥ 6 months
  • 1st line: SSRIs or CBT
  • Performance-only subtype: beta-blockers or BZD
AgoraphobiaFear of being in situations or places where it is difficult to leave or escape≥ 6 months1st line: SSRIs or CBT
Separation anxiety disorderAnxiety arises from the fear of being separated from attachment figures.≥ 1 month
  • 1st line: CBT
  • Medications can be used if CBT alone fails.
Illness anxiety disorderAnxiety arises from concerns about having or acquiring a certain illness.≥ 6 months
  • Schedule regular followup visits.
  • Avoid doing unnecessary diagnostic tests.
  • Avoid referrals.
  • CBT and antidepressants if these measures fail
Substance- or drug-induced anxiety disorder
  • Intoxication with cocaine or amphetamine
  • Withdrawal from alcohol or BZD
  • Medications such as beta-2 agonists (albuterol) or levothyroxine

Differential Diagnosis

  • Intoxication (cocaine or amphetamines): patients with cocaine use disorder or amphetamine use disorder are predisposed to anxiety when they are intoxicated with either substance. Symptoms include agitation, psychosis, hemodynamic instability (hypertension, tachycardia), diaphoresis, and mydriasis. Acute intoxication is distinguished from GAD by history taking, physical exam, and urine toxicology screen. 
  • Withdrawal (from alcohol or benzodiazepines): patients with alcohol use disorder or anxiolytic use disorder are at an increased risk of withdrawal if they discontinue their substance use abruptly. Symptoms include worsening of initial anxiety, insomnia, psychosis, and seizures. Withdrawals from alcohol and anxiolytics are distinguished from GAD by history taking, physical exam, and urine toxicology screen. 
  • Major depressive disorder: a disorder marked by depressed mood, sleep disturbance, anhedonia, feelings of guilt or worthlessness, loss of energy, low concentration, weight or appetite changes, psychomotor retardation or agitation, and suicidal ideation. These symptoms last for ≥ 2 weeks. Excessive worry is a common feature of major depressive disorder and a diagnosis of GAD may be made alongside MDD if anxiety symptoms are sufficiently severe. 
  • Panic disorder: a condition marked by recurrent and episodic panic attacks that occur abruptly and without a trigger. Unlike GAD, these time-limited panic attacks present with cardiorespiratory (palpitations, shortness of breath, choking), GI (nausea, abdominal distress), and neurologic (paresthesias, lightheadedness) symptoms. Fear of dying or “going crazy” can occur. Patients may develop agoraphobia, which is the fear of being in places or situations where leaving or escape is difficult. 
  • Obsessive-compulsive disorder (OCD): a condition characterized by recurring intrusive thoughts, feelings, or sensations (known as obsessions) that are time consuming and cause severe distress. Symptoms are relieved partially by the performance of repetitive actions (known as compulsions). Detailed history taking will reveal that the excessive worry from GAD comes from upcoming issues, while in OCD the worry is more inappropriate and consists of intrusive ideas.

References

  1. Baldwin, D. (2021). Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis. UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis
  2. Craske, M. (2021). Approach to treating generalized anxiety disorder in adults. UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/approach-to-treating-generalized-anxiety-disorder-in-adults
  3. Dave, P. (2017). Clinical management of anxiety disorders. https://www.researchgate.net/publication/348489972_Clinical_Management_of_Anxiety_Disorders
  4. Grant, J. (2021). Overview of anxiety disorders. https://www.researchgate.net/publication/348435567_Overview_of_Anxiety_Disorders
  5. Palkar, P. (2020). Neurobiology of anxiety disorders. https://www.researchgate.net/publication/341407589_Neurobiology_of_Anxiety_Disorders
  6. Sadock, B. J., Sadock, V. A., & Ruiz, P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 9, Anxiety Disorders, pages 387-417. Philadelphia, PA: Lippincott Williams and Wilkins.

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