What is the first-line treatment for an adult with generalized anxiety disorder?

First-Line Treatment for Anxiety in Adults

The first-line treatment for an adult with generalized anxiety disorder is either an SSRI (escitalopram 10-20 mg/day or sertraline 50-200 mg/day) or cognitive behavioral therapy (CBT), with escitalopram and sertraline preferred as top-tier pharmacologic agents due to their superior efficacy, favorable side effect profiles, and lower discontinuation symptom rates. 1

Pharmacotherapy Approach

Preferred First-Line SSRIs

• Escitalopram should be started at 5-10 mg daily, then titrated by 5-10 mg increments every 1-2 weeks, targeting 10-20 mg/day 1
• Sertraline should be initiated at 25-50 mg daily, then increased by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day 1
• Both agents demonstrate comparable efficacy to SNRIs with small to medium effect sizes compared to placebo (standardized mean difference -0.55 for GAD) 2

Expected Timeline for Response

• Statistically significant improvement begins by week 2 1
• Clinically significant improvement occurs by week 6 1
• Maximal therapeutic benefit is achieved by week 12 or later 1
• Do not abandon treatment prematurely; full response may require 12+ weeks 3

Critical Monitoring Requirements

• All SSRIs carry a boxed warning for suicidal thinking and behavior, requiring close monitoring especially in the first months and following dose adjustments 1
• Assess response using standardized anxiety rating scales such as GAD-7 or HAM-A 3
• Monitor for common side effects including nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, and dizziness 3
• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 3

Cognitive Behavioral Therapy

Structure and Duration

• CBT should be delivered as approximately 12-20 individual sessions over 3-4 months, with each session lasting 60-90 minutes 1
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness (Hedges g = 1.01 for GAD, representing a large effect size) 1
• CBT demonstrates comparable efficacy to pharmacotherapy with potentially more durable long-term benefits 4

Core CBT Components

• Psychoeducation on anxiety mechanisms and symptoms 1
• Cognitive restructuring to challenge distorted thinking patterns 1
• Relaxation techniques including breathing exercises and progressive muscle relaxation 1
• Gradual exposure to feared situations when appropriate 1
• Relapse prevention strategies 1

Combined Treatment Approach

For patients with moderate to severe anxiety, combination treatment (SSRI + CBT) provides superior outcomes compared to either treatment alone 1

• Consider combined therapy when initial monotherapy produces inadequate response 3
• Combination is particularly beneficial for patients with significant functional impairment 3

Second-Line Options

When to Switch Treatment

• If inadequate response after 8-12 weeks at therapeutic SSRI doses despite good adherence, modify the treatment strategy 3
• Consider switching to a different SSRI (paroxetine 10-40 mg/day or fluvoxamine 50-300 mg/day) 1
• Alternatively, switch to an SNRI such as venlafaxine extended-release 75-225 mg/day or duloxetine 60-120 mg/day 1

SNRI Considerations

• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension 1
• Duloxetine offers additional benefits for patients with comorbid pain conditions 3
• SNRIs demonstrate similar efficacy to SSRIs with standardized mean difference of -0.55 for GAD 2

Medications to Avoid

• Benzodiazepines should be reserved only for short-term use (days to a few weeks) due to high risks of dependence, tolerance, cognitive impairment, and withdrawal 1
• Bupropion is contraindicated for anxiety disorders as it is activating and can exacerbate anxiety symptoms 1
• Beta blockers (atenolol, propranolol) are deprecated based on negative evidence 1
• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Antipsychotics such as quetiapine are not recommended based on negative evidence 1

Maintenance Treatment

Duration of Therapy

• After achieving remission, continue pharmacotherapy for at least 6-12 months for first episode of anxiety 1
• For recurrent anxiety, long-term or indefinite treatment may be beneficial 1
• Periodically reassess need for continued treatment using standardized anxiety rating scales 1

Discontinuation Strategy

• When discontinuing, taper gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine 1
• A gradual dose reduction rather than abrupt cessation is recommended whenever possible 5
• If intolerable symptoms occur following dose decrease, resuming the previously prescribed dose may be considered, then decreasing at a more gradual rate 5

Adjunctive Non-Pharmacological Interventions

• Recommend structured physical activity and exercise, which provides moderate to large reduction in anxiety symptoms 1
• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, and mindfulness are useful adjuncts 1
• Provide psychoeducation to family members about anxiety symptoms and treatment 1
• Address sleep hygiene, as insomnia commonly co-occurs with anxiety 3
• Advise patients to avoid excessive caffeine and alcohol, as both can exacerbate anxiety symptoms 3

Special Populations

• For elderly patients, 10 mg/day escitalopram is the recommended dose 5
• For patients with hepatic impairment, 10 mg/day escitalopram is recommended 5
• No dosage adjustment is necessary for patients with mild or moderate renal impairment 5
• Escitalopram should be used with caution in patients with severe renal impairment 5

Clinical Pitfalls to Avoid

• Do not escalate doses too quickly; allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 3
• Do not commence pharmacotherapy for mild anxiety before trialing evidence-based non-pharmacologic interventions such as CBT 3
• Do not overlook functional impairment assessment; significant impairment may justify treatment despite low symptom scores 3
• Patients with anxiety pathology commonly avoid follow-through on referrals, so proactively assess and address barriers to treatment adherence 3
• Screen for bipolar disorder prior to initiating SSRI treatment, as antidepressants can precipitate manic episodes 5