What is the recommended treatment for a patient with general anxiety disorder?

Treatment of Generalized Anxiety Disorder

Start with either an SSRI (escitalopram 10-20 mg/day or sertraline 50-200 mg/day) or an SNRI (duloxetine 60-120 mg/day or venlafaxine 75-225 mg/day) as first-line pharmacotherapy, combined with individual cognitive behavioral therapy for optimal outcomes. 1

First-Line Pharmacological Treatment

Preferred SSRI Options

• Escitalopram and sertraline are the top-tier first-line agents due to their established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs 1
• Start escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks to a target of 10-20 mg/day 1
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks to a target of 50-200 mg/day 1
• Begin with lower doses to minimize initial anxiety or agitation that commonly occurs when starting SSRIs 1

Alternative SSRI Options (Second-Tier)

• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 1
• Fluoxetine 20-40 mg/day has a longer half-life that may benefit patients who occasionally miss doses 1

SNRI Options

• Duloxetine 60-120 mg/day has demonstrated efficacy in GAD and provides additional benefits for patients with comorbid pain conditions 1
• Start duloxetine at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1
• Venlafaxine extended-release 75-225 mg/day is effective for GAD but requires blood pressure monitoring due to risk of sustained hypertension 1

Expected Response Timeline and Monitoring

Timeline for Improvement

• Statistically significant improvement may begin by week 2 1
• Clinically significant improvement is expected by week 6 1
• Maximal therapeutic benefit is achieved by week 12 or later 1
• Do not abandon treatment before 12 weeks at therapeutic doses, as SSRI/SNRI response follows a logarithmic pattern with continued improvement over time 1

Critical Monitoring Requirements

• Monitor for suicidal thinking and behavior, especially in the first months and following dose adjustments, with pooled risk of 1% versus 0.2% for placebo (NNH = 143) 1
• Assess response using standardized anxiety rating scales such as GAD-7 or HAM-A 1
• Monitor for common side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, somnolence, and dizziness 1
• Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 1

Cognitive Behavioral Therapy Integration

CBT as First-Line Treatment

• Individual CBT is equally effective as first-line treatment and should be offered based on patient preference and availability 1
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness, with large effect sizes for GAD (Hedges g = 1.01) 1
• A structured duration of 12-20 CBT sessions is recommended to achieve significant symptomatic and functional improvement 1

Combination Therapy

• Combining medication with CBT provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety 1
• CBT should include education on anxiety, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate 1

Treatment Algorithm for Inadequate Response

If First Medication Trial Fails

• After 8-12 weeks at therapeutic doses with inadequate response, switch to a different SSRI or SNRI 1
• Use a gradual cross-taper: reduce the first medication by 25-50 mg every 1-2 weeks while simultaneously starting the new medication at a low dose 1
• Consider adding CBT if not already implemented 1

Second-Line Medication Options

• Pregabalin or gabapentin can be considered when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions 1

Long-Term Management

Treatment Duration

• Continue effective medication for a minimum of 9-12 months after achieving remission to prevent relapse 1
• Reassess monthly until symptoms stabilize, then every 3 months 1
• Alter treatment strategy if no improvement after 8 weeks at therapeutic doses despite good adherence 1

Discontinuation Strategy

• Taper medication gradually over at least 10-14 days to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like sertraline and paroxetine 1
• Discontinuation symptoms are more severe with paroxetine and fluvoxamine compared to escitalopram and sertraline 1

Critical Pitfalls to Avoid

Medications to Avoid

• Avoid tricyclic antidepressants (TCAs) due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Benzodiazepines should be reserved for short-term use only due to risks of dependence, tolerance, and withdrawal 1, 2
• Benzodiazepines lack antidepressant efficacy important for addressing comorbid depression experienced by many GAD patients 3

Dosing Errors

• Do not escalate doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window 1
• Do not discontinue medication abruptly, as this increases risk of withdrawal symptoms and relapse 1

Treatment Adherence

• Patients with anxiety pathology commonly avoid follow-through on referrals—proactively assess and address barriers to treatment adherence 1

Adjunctive Non-Pharmacological Strategies

Lifestyle Modifications

• Structured physical activity and exercise provide moderate to large reduction in anxiety symptoms 1
• Avoid excessive caffeine and alcohol, as both can exacerbate anxiety symptoms 1
• Sleep hygiene education should address insomnia, which commonly co-occurs with anxiety 1

Additional Techniques

• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, and mindfulness are useful adjunctive strategies 1
• Regular cardiovascular exercise and activities of enjoyment are recommended 1

Special Considerations

Comorbidity Screening

• Approximately one-third of GAD patients have comorbid conditions such as depression, substance use, and other psychiatric disorders—screen for these conditions as they may influence treatment selection 1
• Rule out medical causes including hyperthyroidism, caffeinism, hypoglycemia, asthma exacerbations, and cardiac arrhythmias before initiating treatment 1

Buspirone as Alternative

• Buspirone is FDA-approved for GAD management and may be considered, though it lacks the antidepressant efficacy of SSRIs/SNRIs 4, 3
• Buspirone effectiveness beyond 3-4 weeks has not been demonstrated in controlled trials, though long-term use up to 1 year has been studied without ill effect 4