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

Initial Treatment for Generalized Anxiety Disorder

Start with either an SSRI (escitalopram or sertraline preferred) or SNRI (duloxetine or venlafaxine) as first-line pharmacological treatment, with cognitive behavioral therapy (CBT) as the initial treatment approach for most patients. 1, 2

Treatment Algorithm

Step 1: Initial Assessment and Treatment Selection

Psychological therapy (predominantly CBT) is the initial treatment approach for most patients based on 246 RCTs showing improved symptoms and decreased relapse rates compared to waitlist controls, active treatment groups, usual care, or psychological placebos. 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). 2
• CBT demonstrates efficacy comparable to or exceeding pharmacotherapy alone for anxiety disorders. 2

Step 2: First-Line Pharmacotherapy (When Medication is Indicated)

SSRIs and SNRIs are first-line pharmacological treatments due to their established efficacy and favorable safety profiles. 2

Preferred SSRI Options:

• Escitalopram: Start 10 mg once daily (can increase to 20 mg after minimum of one week if needed). 3
• Sertraline: Start 25-50 mg daily, titrate by 25-50 mg increments every 1-2 weeks as tolerated, target dose 50-200 mg/day. 2

These are top-tier first-line agents due to established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs. 2

Alternative SSRI Options (Second-Tier):

• Fluoxetine and fluvoxamine are effective but fluoxetine has a longer half-life that may benefit patients who occasionally miss doses. 2
• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail. 2

SNRI Options:

• Duloxetine: 60-120 mg/day has demonstrated efficacy in GAD and additional benefits for patients with comorbid pain conditions. 2
• Venlafaxine extended-release: 75-225 mg/day is effective but requires blood pressure monitoring due to risk of sustained hypertension. 2

Step 3: Dosing Strategy

Begin with lower doses and titrate gradually to minimize side effects. 2

• Start escitalopram at 5-10 mg daily, titrate by 5-10 mg increments. 2
• For duloxetine, start at 30 mg daily for one week to reduce nausea, then increase to 60 mg. 2
• A subtherapeutic "test" dose may be advisable initially since SSRIs can cause anxiety or agitation as an initial adverse effect. 1

Step 4: Monitoring and Timeline

Response typically follows a logarithmic model:

• Statistically significant improvement within 2 weeks 2
• Clinically significant improvement by week 6 2
• Maximal improvement by week 12 or later 2

Assess response using standardized anxiety rating scales (e.g., HAM-A). 2

Monitor for common side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams. 2

Most adverse effects emerge within the first few weeks of treatment. 2

Step 5: Inadequate Response (After 8-12 Weeks at Therapeutic Doses)

Switch to a different SSRI or SNRI (e.g., sertraline to escitalopram or vice versa). 2

Consider adding CBT if not already implemented. 2

Step 6: Second-Line Options

Pregabalin/Gabapentin can be considered when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions. 2

Treatment Duration and Discontinuation

Generalized anxiety disorder is recognized as a chronic condition. 3

• Continue treatment for at least 12 months if at least moderate clinical response is achieved. 4
• Periodically re-evaluate the long-term usefulness for the individual patient. 3

Discontinue medication gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs (notably paroxetine, but also fluvoxamine and sertraline). 1, 2

A discontinuation syndrome characterized by dizziness, fatigue, lethargy, myalgias, headaches, nausea, insomnia, vertigo, paresthesias, anxiety, and irritability has been reported following missed doses or acute discontinuation. 1

Critical Warnings and Pitfalls

Avoid tricyclic antidepressants (TCAs) due to their unfavorable risk-benefit profile, particularly cardiac toxicity. 2

Paroxetine has higher risk of discontinuation syndrome and potentially increased suicidal thinking compared to other SSRIs. 2

Screen for bipolar disorder prior to initiating treatment with escitalopram or another antidepressant by assessing personal and family history of bipolar disorder, mania, or hypomania. 3

At least 14 days should elapse between discontinuation of an MAOI and initiation of SSRI/SNRI therapy, and vice versa. 3

Monitor venlafaxine for blood pressure increases and discontinuation symptoms. 2

Special Populations

Elderly patients and those with hepatic impairment: 10 mg/day escitalopram is the recommended dose. 3

Severe renal impairment: Use escitalopram with caution; no dosage adjustment necessary for mild or moderate renal impairment. 3