What is the treatment for a patient with Generalized Anxiety Disorder (GAD)?

Treatment of Generalized Anxiety Disorder (GAD)

Start with an SSRI (escitalopram 10-20 mg/day or sertraline 50-200 mg/day) combined with cognitive behavioral therapy (CBT), as this combination provides optimal outcomes for GAD. 1

First-Line Pharmacotherapy

SSRIs are the preferred first-line medications due to their established efficacy and favorable safety profile compared to alternatives 2, 1:

• Escitalopram: Start 5-10 mg daily, titrate by 5-10 mg increments every 1-2 weeks to target dose of 10-20 mg/day 1
• Sertraline: Start 25-50 mg daily, titrate by 25-50 mg increments every 1-2 weeks to target dose of 50-200 mg/day 1
• Paroxetine: Reserve as second-tier due to higher discontinuation syndrome risk and potentially increased suicidal thinking 1

SNRIs are equally effective alternatives 2, 1:

• Venlafaxine: Monitor blood pressure regularly; effective for GAD with sustained long-term benefit 1, 3, 4
• Duloxetine: Start 30 mg daily for one week to reduce nausea, then increase to 60 mg 1

Psychotherapy Integration

Combine medication with individual CBT from the start rather than using either alone, as combination therapy achieves superior outcomes 1:

• Individual CBT is superior to group therapy for GAD, with large effect sizes (Hedges g = 1.01) 1
• CBT components should include: education on anxiety mechanisms, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate 1
• Applied relaxation and cognitive therapy are also effective psychotherapeutic approaches 3, 4

Timeline and Monitoring

Expect statistically significant improvement by week 2, clinically significant improvement by week 6, and maximal benefit by week 12 or later 1:

• Assess response using standardized scales (GAD-7 or HAM-A) at regular intervals 2, 1
• Monitor closely for suicidal thinking, especially in the first months and after dose adjustments (pooled risk difference 0.7% vs placebo, NNH=143) 1
• Assess compliance monthly until symptoms subside, as patients with anxiety often avoid follow-through 1

Treatment Duration

Continue medication for at least 9-12 months after recovery to prevent relapse, as GAD is a chronic condition requiring long-term treatment 1, 5:

• Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine and sertraline 1
• Stopping medication within the first year increases relapse risk 5

Medications to Avoid as First-Line

Do not use benzodiazepines as first-line treatment despite their FDA approval for GAD 6, 7:

• Reserve for short-term adjunctive use only during acute crises due to risks of dependence, cognitive impairment, and failure to address underlying pathology 1
• They lack antidepressant efficacy needed for the high comorbidity with depression (62% with major depression, 37% with dysthymia) 5, 8

Avoid tricyclic antidepressants due to unfavorable risk-benefit profile, particularly cardiac toxicity 1

Buspirone has limited utility despite FDA approval 6:

• Shows anxiolytic benefits but negligible antidepressant action, making it less ideal given high depression comorbidity 4

Special Populations and Comorbidities

For children and adolescents (6-18 years), SSRIs are recommended with moderate to high evidence for improving anxiety symptoms, treatment response, remission, and global function 2:

• Fluoxetine, fluvoxamine, paroxetine, and sertraline have sufficient data supporting their use 2
• No specific SSRIs have FDA approval for pediatric anxiety, but the class is effective 2

For patients with comorbid depression (present in majority of GAD cases), antidepressants are more likely to succeed than benzodiazepines or buspirone 5, 8

Common Pitfalls to Avoid

• Inadequate follow-up: Patients with anxiety frequently avoid follow-through on referrals; ensure monthly assessment until symptom resolution 1
• Premature discontinuation: Stopping medication before 9-12 months increases relapse risk 1, 5
• Using benzodiazepines long-term: This creates dependence without addressing underlying pathology 1
• Underdosing or inadequate trial duration: Allow 12 weeks for maximal benefit before declaring treatment failure 1