What is the recommended treatment for a patient with Generalized Anxiety Disorder (GAD) experiencing panic attacks?

Treatment of Generalized Anxiety Disorder with Panic Attacks

Start with an SSRI (escitalopram 10-20 mg/day or sertraline 50-200 mg/day) as first-line pharmacotherapy, combined with cognitive behavioral therapy for optimal outcomes. 1

First-Line Pharmacological Treatment

SSRIs and SNRIs are the recommended first-line medications due to their established efficacy and favorable safety profiles. 1

Preferred SSRI Options:

• 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
• Fluoxetine: Start 5-10 mg daily, increase by 5-10 mg every 1-2 weeks, targeting 20-40 mg daily by weeks 4-6; longer half-life may benefit patients who occasionally miss doses 1

Alternative First-Line: SNRIs

• Duloxetine: 60-120 mg/day; particularly beneficial for patients with comorbid pain conditions 1, 2
• Venlafaxine extended-release: 75-225 mg/day; requires blood pressure monitoring due to risk of sustained hypertension 1

Expected Response Timeline

Patience is critical during initial treatment. Response follows a logarithmic pattern: 1

• Statistically significant improvement may begin by week 2
• Clinically significant improvement expected by week 6
• Maximal therapeutic benefit achieved by week 12 or later

Do not abandon treatment prematurely or escalate doses too quickly—allow 1-2 weeks between dose increases to assess tolerability. 1

Combination with Psychotherapy

Combining medication with CBT provides optimal outcomes and should be initiated concurrently. 1 Individual CBT is superior to group therapy for GAD, with large effect sizes (Hedges g = 1.01). 1

CBT should include: 1

• Education on anxiety mechanisms
• Cognitive restructuring to challenge distortions
• Relaxation techniques (progressive muscle relaxation)
• Gradual exposure when appropriate
• 12-20 structured sessions for significant improvement

Monitoring and Safety

Common Side Effects (emerge within first few weeks):

• Nausea, sexual dysfunction, headache, insomnia 1
• Dry mouth, diarrhea, heartburn, somnolence, dizziness 1
• Most adverse effects resolve with continued treatment 1

Critical Monitoring:

• Assess response using standardized scales (GAD-7 or HAM-A) at regular intervals 1
• Monitor closely for suicidal thinking, especially in first months and after dose adjustments (pooled risk difference 0.7% vs placebo, NNH=143) 1
• For duloxetine: Start at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1
• For venlafaxine: Monitor blood pressure regularly 1

If First SSRI Fails

After 8-12 weeks at therapeutic doses with inadequate response: 1

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa)
• Consider switching to an SNRI (duloxetine or venlafaxine)
• Ensure CBT is implemented if not already in place

Second-Line Options

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

Treatment Duration

Continue medication for at least 9-12 months after recovery to prevent relapse. 3 GAD is often chronic and requires long-term treatment; stopping medication increases relapse risk within the first year. 4, 5

Discontinue gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like paroxetine and sertraline. 1

Medications to Avoid

Avoid benzodiazepines as first-line treatment despite their rapid onset—they carry risks of dependence, cognitive impairment, and do not address underlying pathology. 1 Reserve for short-term adjunctive use only during acute crises.

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

Paroxetine should be reserved for when first-tier SSRIs fail due to higher risk of discontinuation syndrome and potentially increased suicidal thinking. 1

Common Pitfalls

• Starting doses too high: Begin with lower doses to minimize initial anxiety/agitation that can occur with SSRIs 1
• Abandoning treatment too early: Full response requires 12+ weeks 1
• Escalating doses too rapidly: Allow adequate time between increases 1
• Failing to combine with CBT: Medication alone is less effective than combination therapy 1
• Inadequate follow-up: Patients with anxiety often avoid follow-through on referrals; assess compliance monthly until symptoms subside 3