Generalized Anxiety Disorder (GAD): Clinical Presentation

Abstract

Generalized Anxiety Disorder (GAD) is a chronic psychiatric condition characterized by excessive, uncontrollable worry and somatic symptoms persisting ≥6 months. This article reviews DSM-5 diagnostic criteria, neurobiological mechanisms, and first-line treatments (CBT, pharmacotherapy) based on current clinical guidelines.

1. Diagnostic Criteria (DSM-5)

GAD requires:

• Excessive anxiety and worry occurring more days than not for ≥6 months

• Difficulty controlling worry

• ≥3 of the following symptoms:

  • Restlessness/feeling keyed up

  • Fatigue

  • Impaired concentration

  • Irritability

  • Muscle tension

  • Sleep disturbance

• Clinically significant distress/impairment

• Not attributable to substances or medical conditions

Differential diagnoses: Thyroid disorders, cardiac arrhythmias, stimulant misuse.

2. Epidemiology and Risk Factors

• Prevalence: 3.1% U.S. adults (12-month), 5.7% lifetime (NIMH)

• Female:Male ratio: 2:1

• Mean onset: 31 years (often earlier, with 25% onset by age 11)

Risk stratification:

• Genetic: 3-5× increased risk with first-degree relative

• Neurobiological: Amygdala hyperactivity, prefrontal cortex dysregulation

• Environmental: Childhood adversity (OR=2.5), chronic stress

3. Pathophysiology

Current models implicate:

1. Neurotransmitter dysregulation:

   • ↓ GABAergic inhibition

   • ↓ Serotonin (5-HT1A receptor desensitization)

   • ↑ Noradrenergic activity

2. Functional neuroanatomy:

   • Hyperactivity in amygdala-insular circuit

   • Hypoactivation of prefrontal regulatory regions

3. HPA axis abnormalities: Elevated cortisol response to stressors

4. Clinical Assessment

Standardized Measures

• GAD-7 (≥10 indicates moderate-severe symptoms)

• Penn State Worry Questionnaire

• Hamilton Anxiety Rating Scale (HAM-A)

Laboratory Workup

• TSH, CBC, CMP, EKG (rule out hyperthyroidism, arrhythmias)

• Urine drug screen (stimulants, caffeine)

5. Evidence-Based Treatment Algorithms

First-Line Pharmacotherapy

Second-line:

• Buspirone (5-HT1A partial agonist)

• Pregabalin (Ca2+ channel modulator)

Avoid long-term benzodiazepines (risk of dependence, cognitive effects).

Psychotherapy

1. Cognitive Behavioral Therapy (CBT):

   • Cognitive restructuring of catastrophizing

   • Worry exposure experiments

   • Meta-cognitive therapy for “worry about worry”

2. Acceptance and Commitment Therapy (ACT):

   • Defusion techniques

   • Values-based action

Efficacy: CBT shows 60% response rate vs. 40% for meds alone (APA guidelines).

6. Prognosis and Comorbidities

• Chronic course: 50% relapse without maintenance therapy

• Common comorbidities:

  • Major depressive disorder (62%)

  • Other anxiety disorders (59%)

  • Somatic symptom disorders

Mortality: 2× increased cardiovascular risk (chronic sympathetic activation).

7. Emerging Treatments

• rTMS (right DLPFC target)

• Psilocybin-assisted therapy (Phase II trials)

• Digital therapeutics (FDA-approved CBT apps)

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8. Patient Education Points

• “Worry is not preparation” – neural habituation takes 6-8 weeks of CBT

• Medication adherence critical (early side effects often transient)

• Sleep hygiene optimization doubles treatment response

Provider Resources:

• APA Practice Guidelines

• NICE Clinical Guidelines