What are the recommended treatments for a patient with generalized anxiety disorder?

Treatment of Generalized Anxiety Disorder

First-Line Treatment Recommendation

For adults with generalized anxiety disorder, initiate treatment with either escitalopram (10 mg daily) or sertraline (25-50 mg daily) as first-line pharmacotherapy, combined with cognitive behavioral therapy when available, as this combination provides superior outcomes compared to either treatment alone. 1

Treatment Algorithm

Step 1: Initial Pharmacotherapy Selection

SSRIs are the preferred first-line agents:

• Escitalopram: Start 10 mg once daily (morning or evening, with or without food); may increase to 20 mg after minimum 1 week if needed 2
• Sertraline: Start 25-50 mg daily; titrate by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day 1

SNRIs as alternative first-line options:

• Duloxetine: 60-120 mg/day, particularly beneficial for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea 1
• Venlafaxine extended-release: 75-225 mg/day, requires blood pressure monitoring due to risk of sustained hypertension 1, 3

Step 2: Expected Response Timeline

• Week 2: Statistically significant improvement may begin 1
• Week 6: Clinically significant improvement expected 1
• Week 12 or later: Maximal therapeutic benefit achieved 1

Critical caveat: Do not abandon treatment prematurely; full response requires patience and adequate trial duration of 8-12 weeks at therapeutic doses before declaring treatment failure 1

Step 3: If Inadequate Response After 8-12 Weeks

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 1
• Consider switching to an SNRI if not already tried 1
• Add or intensify cognitive behavioral therapy 1

Step 4: Second-Line Options

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

Cognitive Behavioral Therapy Integration

CBT is equally effective as first-line treatment and should be offered based on patient preference:

• Individual CBT is superior to group therapy for clinical and cost-effectiveness 1
• Recommended duration: 12-20 structured sessions 1
• Core elements include: psychoeducation on anxiety, cognitive restructuring to challenge distortions (catastrophizing, over-generalization, negative prediction), relaxation techniques, and graduated exposure when appropriate 4
• Combination treatment (SSRI + CBT) provides superior outcomes compared to either alone, particularly for moderate to severe anxiety 1

Critical Monitoring Requirements

Side Effect Monitoring

Common adverse effects (emerge within first few weeks, typically resolve with continued treatment):

• Nausea, diarrhea, dry mouth, heartburn 1
• Headache, dizziness, somnolence or insomnia 1
• Sexual dysfunction 1
• Nervousness and tremor 1

Safety Monitoring

Black box warning: All SSRIs carry risk for suicidal thinking and behavior (pooled absolute rates 1% vs 0.2% placebo; number needed to harm = 143) 1

• Monitor closely, especially in first months and following dose adjustments 1

For venlafaxine: Monitor blood pressure regularly due to risk of sustained hypertension 1

For duloxetine: Nausea is common but can be reduced by starting at 30 mg daily for one week before increasing 1

Maintenance Treatment Duration

• Continue medications for 6-12 months after remission 3
• Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs 1
• Periodically reassess need for continued treatment 2

Medications to AVOID

Benzodiazepines should be avoided as first-line treatment due to risks of dependence, tolerance, and withdrawal; reserve only for short-term use 1

Tricyclic antidepressants (TCAs) should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1

Beta blockers (atenolol, propranolol) are not recommended based on negative evidence 1

Special Populations

• Elderly patients and those with hepatic impairment: 10 mg/day escitalopram is recommended dose 2
• Severe renal impairment: Use escitalopram with caution 2

Important Clinical Pitfalls

Do not escalate SSRI doses too quickly - allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window, as SSRI response follows a logarithmic model with diminishing returns at higher doses 1

Screen for bipolar disorder prior to initiating antidepressant treatment to avoid precipitating manic episodes 2

Rule out substance-induced anxiety and ensure symptoms are not caused by drugs of abuse, pharmaceuticals, or other medical conditions 1

Screen for comorbidities: Approximately one-third of GAD patients have comorbid depression, substance use, or other psychiatric disorders 1