What are the symptoms and treatment options for generalized anxiety disorder?

Generalized Anxiety Disorder: Symptoms and Treatment

Core Symptoms of GAD

Generalized anxiety disorder is characterized by excessive, uncontrollable worry about multiple everyday situations or activities (work, school, family, finances, health, social relationships) that persists for at least 6 months and causes clinically significant distress or functional impairment. 1, 2

Psychological Symptoms

• Excessive worry that is difficult to control about numerous events and activities 2, 3
• Apprehensive expectation and rumination about potential misfortune 3
• Feeling nervous, anxious, or on edge 1
• Difficulty concentrating or mind going blank 2
• Irritability 1, 2
• Fear and hypervigilance 3

Physical (Somatic) Symptoms

• Restlessness or feeling keyed up 1, 2
• Being easily fatigued 2, 4
• Muscle tension and muscle aches 2, 4
• Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep) 2, 4
• Autonomic hyperactivity: sweating, palpitations, dizziness, gastrointestinal distress, trembling 1, 3

Important caveat: Somatic symptoms are particularly prominent in non-Western populations and Spanish-speaking Latinos, who may present primarily with physical complaints rather than psychological worry. 1 Missing these presentations leads to underdiagnosis in these populations.

Functional Impairment Required for Diagnosis

• Symptoms must cause significant impairment in social, occupational, academic, or other important areas of functioning 1, 2
• Home, relationship, work, or school performance must be affected 1

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First-Line Treatment Approach

Start with an SSRI (escitalopram 10-20 mg/day or sertraline 50-200 mg/day) or SNRI (duloxetine 60-120 mg/day or venlafaxine 75-225 mg/day) combined with individual cognitive behavioral therapy for optimal outcomes. 5

Specific Medication Regimens

Escitalopram (top-tier first-line):

• Start 5-10 mg daily 5
• Titrate by 5-10 mg increments every 1-2 weeks 5
• Target dose: 10-20 mg/day 5

Sertraline (equally preferred):

• Start 25-50 mg daily 5
• Titrate by 25-50 mg increments every 1-2 weeks 5
• Target dose: 50-200 mg/day 5

Duloxetine:

• Start 30 mg daily for one week to reduce nausea 5
• Increase to 60 mg after first week 5
• Target dose: 60-120 mg/day 5
• Particularly beneficial for comorbid pain conditions 5

Venlafaxine extended-release:

• Target dose: 75-225 mg/day 5, 6, 7
• Monitor blood pressure regularly due to risk of sustained hypertension 5

Expected Timeline for Response

• Statistically significant improvement may begin by week 2 5
• Clinically significant improvement expected by week 6 5
• Maximal therapeutic benefit achieved by week 12 or later—do not abandon treatment prematurely 5
• Full response may require 12+ weeks 5

Monitoring Requirements

• Assess response using standardized scales (GAD-7 or HAM-A) at regular intervals 5
• Monitor closely for suicidal thinking and behavior, especially in first months and after dose adjustments (pooled risk difference 0.7% vs placebo, NNH=143) 5
• Assess monthly for treatment adherence until symptoms subside, as patients with anxiety commonly avoid follow-through on referrals 1, 5

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Cognitive Behavioral Therapy (Essential Component)

Individual CBT must be initiated concurrently with medication for best results. 5

CBT Structure and Components

• 12-20 individual sessions of 60-90 minutes each over 3-4 months 5, 8
• Education on anxiety mechanisms 5
• Cognitive restructuring to challenge distorted thinking 1, 5
• Relaxation techniques (breathing exercises, progressive muscle relaxation, grounding strategies) 1, 5
• Behavioral activation and problem-solving 1
• Gradual exposure when appropriate 5
• Relapse prevention strategies are critical as GAD is often chronic 1, 5

Individual CBT is superior to group therapy for GAD, with large effect sizes (Hedges g = 1.01). 5, 8 The combination of CBT with SSRIs provides superior results compared to either treatment alone. 8

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Treatment Duration and Discontinuation

• Continue medication for at least 9-12 months after recovery to prevent relapse 5
• GAD is frequently a chronic condition requiring long-term management 1, 5
• Discontinue medication gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine and sertraline 5
• Reduce dose by approximately 25% every two weeks when discontinuing 8

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Medications to Avoid

Avoid benzodiazepines as first-line treatment due to risks of dependence, cognitive impairment, tolerance, and failure to address underlying pathology. 5 Reserve benzodiazepines for short-term adjunctive use only during acute crises (4-10 weeks maximum). 5, 8

Avoid tricyclic antidepressants due to unfavorable risk-benefit profile, particularly cardiac toxicity. 5, 8

Buspirone is FDA-approved for GAD but lacks antidepressant efficacy, making it less ideal given the high comorbidity of depression with GAD. 3, 6, 7

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Critical Pitfalls to Avoid

• Inadequate follow-up: Patients with anxiety often avoid follow-through on referrals due to avoidance being a cardinal feature of anxiety pathology; assess compliance monthly until symptoms subside 1, 5
• Escalating doses too quickly: Allow 1-2 weeks between increases to assess tolerability 5
• Premature discontinuation: Treatment should not be abandoned before 12 weeks, as maximal benefit takes time 5
• Missing somatic presentations in culturally diverse populations: Spanish-speaking and non-Western patients may present primarily with physical symptoms rather than psychological worry 1
• Failing to screen for comorbid depression: Many GAD patients have coexisting depressive symptoms requiring antidepressant therapy 3, 6