What is the pathophysiology, clinical manifestations, and treatment of anxiety disorder?

Anxiety Disorders: Pathophysiology, Clinical Manifestations, and Treatment

Pathophysiology of Anxiety Disorders

Anxiety disorders result from complex biopsychosocial interactions involving brain circuit dysfunction, genetic vulnerabilities, and environmental factors that lead to excessive fear responses and functional impairment. 1

• Biological Factors:

  • Inherited vulnerabilities in brain structure and function
  • Autonomic hyperreactivity
  • Temperamental traits (negative affectivity, behavioral inhibition)
  • Dysfunction in specific brain circuits that respond to danger
  • Chronic medical conditions 2

• Psychological Vulnerabilities:

  • Maladaptive cognitive schemas
  • Information-processing errors
  • Negative self-evaluations
  • Insecure attachment patterns
  • Ego deficits and unconscious conflicts 2

• Social Vulnerabilities:

  • Stressful/traumatic life events
  • Anxiogenic parenting (overprotection, criticism)
  • Social skills deficits
  • Peer rejection
  • Inappropriate expectations for achievement 2

Clinical Manifestations

Anxiety disorders are characterized by developmentally inappropriate, excessive worry or distress that causes significant impairment in functioning. Key manifestations include:

• Motor Tension:

  • Trembling or feeling shaky
  • Muscle tension, aches, or soreness
  • Restlessness
  • Easy fatigability 3

• Autonomic Hyperactivity:

  • Shortness of breath or smothering sensations
  • Palpitations or accelerated heart rate
  • Sweating or cold clammy hands
  • Dry mouth
  • Dizziness or light-headedness
  • Gastrointestinal distress (nausea, diarrhea)
  • Frequent urination 3

• Vigilance and Scanning:

  • Feeling keyed up or on edge
  • Exaggerated startle response
  • Difficulty concentrating or "mind going blank"
  • Sleep disturbances
  • Irritability 3

• Behavioral Changes:

  • Avoidance behaviors
  • Safety behaviors
  • Reassurance seeking 4

Treatment Approaches

Psychotherapy

Cognitive Behavioral Therapy (CBT) is the psychotherapy with the highest level of evidence for anxiety disorders and should be offered as a first-line treatment option. 1, 5

• Core CBT Elements:

  • Education about anxiety
  • Behavioral goal setting with contingent rewards
  • Self-monitoring for connections between worries/fears, thoughts, and behaviors
  • Relaxation techniques (deep breathing, progressive muscle relaxation)
  • Cognitive restructuring to challenge distortions
  • Graduated exposure to feared stimuli
  • Problem-solving and social skills training 2

• Exposure Therapy:

  • Cornerstone of treatment for specific phobias, social anxiety, and separation anxiety
  • Patient creates a fear hierarchy that is mastered in a stepwise manner
  • May include in vivo exposure, emotive imagery, live modeling, and contingency management 2

• Family-Directed Interventions:

  • Improve parent-child relationships
  • Strengthen family problem-solving and communication skills
  • Reduce parental anxiety
  • Foster anxiety-reducing parenting skills 2

Pharmacotherapy

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line pharmacological treatments for anxiety disorders. 1, 5, 4

• SSRIs/SNRIs:

  • Recommended for patients 6-18 years old with social anxiety, generalized anxiety, separation anxiety, or panic disorder
  • Improve primary anxiety symptoms, response to treatment, remission rates, and global function
  • Should be continued for 6-12 months after remission 2, 5

• Second-Line Options:

  • Buspirone
  • Tricyclic antidepressants
  • Pregabalin
  • Moclobemide 5

• Benzodiazepines:

  • Not recommended for routine use or as primary treatment
  • May be considered for short-term relief of acute symptoms in adults
  • Should be used cautiously with gradual dose reduction when discontinuing 3, 5

Treatment Algorithm

1. Initial Assessment:

   • Evaluate anxiety symptoms, severity, functional impairment
   • Screen for comorbid conditions (depression, substance use)
   • Rule out medical causes of anxiety

2. First-Line Treatment:

   • Mild to moderate anxiety: Start with CBT
   • Moderate to severe anxiety: Consider combination of CBT and SSRI/SNRI
   • Patient preference should be considered 4

3. Medication Selection:

   • Start with an SSRI (e.g., sertraline) at low dose
   • Titrate dose gradually over 3-4 days
   • Allow 4-6 weeks for full therapeutic effect 3, 4

4. Treatment Monitoring:

   • Use standardized symptom rating scales to assess response
   • Monitor for adverse effects
   • Evaluate for suicidal ideation, particularly in adolescents 2

5. Inadequate Response:

   • Optimize current medication dose
   • Switch to alternative SSRI/SNRI
   • Consider augmentation with second-line agents
   • Intensify psychotherapy 6

6. Maintenance and Discontinuation:

   • Continue effective medication for 6-12 months after remission
   • Taper medication gradually when discontinuing (no more than 0.5 mg every 3 days for benzodiazepines) 3, 5

Special Considerations and Pitfalls

• Comorbidities:

  • Anxiety disorders commonly co-occur with depression, ADHD, and substance use disorders
  • Each comorbid condition may require separate treatment plans 2

• Suicide Risk:

  • 24% of adolescents with anxiety disorders report suicidal ideation
  • 6% make suicide attempts
  • Regular assessment of suicide risk is essential 1

• Common Pitfalls:

  • Under-diagnosis and insufficient treatment (less than 20% receive appropriate medication)
  • Overreliance on benzodiazepines for long-term management
  • Failure to address sleep disturbances
  • Inadequate duration of treatment leading to relapse 1, 7

• Long-Term Management:

  • Anxiety disorders are often chronic conditions requiring long-term treatment
  • Remission is attainable but may take several months
  • Risk of relapse increases if medication is stopped within the first year 6