What is the first line treatment for generalized anxiety disorder (GAD)?

First-Line Treatment for Generalized Anxiety Disorder

Start with either an SSRI (escitalopram 10 mg or sertraline 25-50 mg daily) or an SNRI (duloxetine 60 mg or venlafaxine XR 75 mg daily), with escitalopram and sertraline preferred as top-tier agents due to superior tolerability and lower discontinuation risk. 1

Recommended First-Line Pharmacotherapy

SSRIs (Preferred Initial Choice)

• Escitalopram 10 mg once daily is the optimal starting point, with dose increase to 20 mg after minimum 1 week if needed 2
• Sertraline 25-50 mg daily is equally preferred, titrating by 25-50 mg increments every 1-2 weeks to target dose of 50-200 mg/day 1
• These two agents have the most favorable side effect profiles and lowest risk of discontinuation symptoms compared to other SSRIs 1

SNRIs (Equally Effective Alternative)

• Duloxetine 60-120 mg/day is particularly beneficial if comorbid pain conditions exist 1
• Venlafaxine XR 75-225 mg/day is effective but requires blood pressure monitoring due to risk of sustained hypertension 1
• SNRIs demonstrate small to medium effect sizes compared to placebo (SMD -0.55) 3

Medications to Avoid as First-Line

• Paroxetine and fluvoxamine should be reserved for when first-tier SSRIs fail due to higher discontinuation symptoms 1
• Tricyclic antidepressants should be avoided entirely due to unfavorable risk-benefit profile and cardiac toxicity 1

Expected Response Timeline

• Statistically significant improvement occurs within 2 weeks of starting treatment 1
• Clinically significant improvement typically by week 6 1
• Maximal improvement by week 12 or later 1
• If inadequate response after 8-12 weeks at therapeutic doses, switch to a different SSRI or SNRI 1

Combination with Psychotherapy

Add cognitive behavioral therapy (CBT) to pharmacotherapy for optimal outcomes, as combination therapy provides superior results compared to either treatment alone 1, 4

• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 5, 1
• CBT demonstrates large effect sizes for GAD (Hedges g = 1.01) 3

Critical Monitoring Requirements

Side Effects to Anticipate

• Common adverse effects include nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, and dizziness 1
• Most adverse effects emerge within the first few weeks of treatment 1
• For duloxetine, start at 30 mg daily for one week to reduce nausea before increasing to 60 mg 1

Blood Pressure Monitoring

• Required for venlafaxine due to dose-dependent increases in blood pressure 1

Discontinuation Precautions

• Taper gradually rather than abrupt cessation to avoid withdrawal symptoms, particularly with shorter half-life SSRIs 1, 2
• Allow at least 14 days between discontinuing an MAOI and starting an SSRI/SNRI 2

Treatment Duration

• GAD is a chronic condition requiring several months or longer of sustained pharmacological therapy beyond initial response 2
• Maintenance treatment has demonstrated benefit in preventing relapse 2
• Periodically reassess the need for continued treatment, but stopping medication within the first year increases relapse risk 6

Second-Line Options

If first-line SSRIs/SNRIs are ineffective or not tolerated:

• Pregabalin or gabapentin can be considered, particularly for patients with comorbid pain conditions 1
• These agents have shown efficacy in GAD but are reserved for inadequate response to first-line treatments 1

Common Pitfalls to Avoid

• Do not use benzodiazepines as first-line despite their rapid anxiolytic effects, as they lack antidepressant efficacy for comorbid depression and have problematic long-term adverse effects 7, 8
• Do not start at full therapeutic doses - begin low and titrate gradually to minimize initial anxiety/agitation that can occur with SSRIs 1
• Do not discontinue prematurely - allow adequate trial duration of 8-12 weeks at therapeutic doses before declaring treatment failure 1
• Do not forget to screen for bipolar disorder before initiating antidepressant treatment 2