What is the recommended management for Generalized Anxiety Disorder (GAD)?

Management of Generalized Anxiety Disorder

Start with escitalopram 10 mg daily or sertraline 25-50 mg daily as first-line pharmacotherapy, combined with individual cognitive behavioral therapy (CBT) for optimal outcomes. 1, 2

First-Line Pharmacological Treatment

Preferred SSRIs

• Escitalopram 10 mg once daily is the top-tier first-line agent due to established efficacy in three 8-week placebo-controlled trials, favorable side effect profile, minimal drug interactions (least effect on CYP450 isoenzymes), and lower discontinuation symptoms compared to other SSRIs 3, 1, 2
• Sertraline is equally preferred, starting at 25-50 mg daily to minimize initial anxiety/agitation, titrating by 25-50 mg increments every 1-2 weeks to target dose of 50-200 mg/day 3, 1
• Dose escalation for escitalopram to 20 mg should occur only after a minimum of one week at 10 mg if inadequate response 2

Alternative First-Line: SNRIs

• Venlafaxine extended-release 75-225 mg/day is effective when SSRIs fail or are not tolerated, but requires blood pressure monitoring due to risk of sustained hypertension 1, 4, 5, 6
• Duloxetine 60-120 mg/day is particularly beneficial for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea 1, 7

First-Line Psychological Treatment

Cognitive Behavioral Therapy

• Individual CBT is superior to group therapy for clinical and cost-effectiveness, with large effect sizes for GAD (Hedges g = 1.01) 1
• Structure treatment as 12-20 sessions over 3-4 months, each lasting 60-90 minutes 8, 1
• Essential CBT components include: psychoeducation on anxiety, cognitive restructuring to challenge distortions, relaxation techniques (breathing, progressive muscle relaxation), gradual exposure when appropriate, and relapse prevention 8, 1
• Combining medication with CBT provides superior outcomes compared to either treatment alone 1, 4, 5, 6

Expected Timeline and Monitoring

Response Pattern

• Statistically significant improvement begins by week 2, clinically significant improvement expected by week 6, and maximal therapeutic benefit achieved by week 12 or later 1
• Assess treatment response at 4 weeks and 8 weeks using standardized anxiety rating scales (e.g., HAM-A) 3, 1
• Monitor for common SSRI/SNRI side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, dizziness (most emerge within first few weeks and typically resolve) 1

Critical Safety Monitoring

• All SSRIs carry a boxed warning for suicidal thinking and behavior (pooled absolute rates 1% vs 0.2% placebo; NNH = 143), requiring close monitoring especially in the first months and following dose adjustments 1
• Screen for personal or family history of bipolar disorder, mania, or hypomania before initiating treatment 2

Algorithm for Inadequate Response

After 8-12 Weeks at Therapeutic Doses

1. Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 3, 1
2. Switch to an SNRI (venlafaxine or duloxetine) if second SSRI fails 1, 7
3. Add or intensify CBT if not already implemented 3, 1
4. Consider pregabalin as second-line option, particularly for patients with comorbid pain conditions 1, 7

Treatment Duration

Maintenance Therapy

• Continue treatment for at least 12 months after achieving remission for first episode 1, 9
• For recurrent GAD, longer-term or indefinite treatment is beneficial given the chronic, relapsing nature of the disorder 3, 9, 5
• Periodically reassess (every 6-12 months) to determine ongoing need for maintenance treatment 2

Discontinuation Strategy

Tapering Protocol

• Never discontinue SSRIs abruptly—taper gradually over 10-14 days minimum to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 3, 2
• If intolerable symptoms occur during taper, resume previous dose and decrease more gradually 2
• Shorter half-life SSRIs (sertraline, paroxetine) require more careful tapering than longer half-life agents 3, 1

Medications to Avoid or Use with Caution

Not Recommended

• Paroxetine and fluoxetine should generally be avoided: paroxetine has significant anticholinergic properties and higher risk of discontinuation syndrome and suicidal thinking; fluoxetine has very long half-life and extensive CYP2D6 interactions 3, 1
• Benzodiazepines should be reserved for short-term use only (if absolutely necessary for acute management) due to risks of dependence, tolerance, withdrawal, cognitive impairment, falls, and fractures 3, 1
• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Beta blockers (atenolol, propranolol) are not effective for GAD based on negative evidence 8, 1

Special Populations

Elderly Patients

• Start escitalopram at 10 mg daily maximum for most elderly patients (no further titration) 3, 2
• Use "start low, go slow" approach with all SSRIs/SNRIs in elderly due to increased sensitivity 3
• Avoid citalopram doses >20 mg daily in patients >60 years old due to QT prolongation risk 3

Hepatic Impairment

• Maximum dose 10 mg/day escitalopram for patients with hepatic impairment 2

Renal Impairment

• No dosage adjustment necessary for mild or moderate renal impairment; use with caution in severe renal impairment 2

Adjunctive Non-Pharmacological Interventions

• Regular cardiovascular exercise provides moderate to large reduction in anxiety symptoms 1
• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, mindfulness, and sensory grounding techniques are useful adjuncts 1
• Provide psychoeducation to family members about anxiety symptoms and treatment 1

Common Pitfalls to Avoid

• Do not abandon treatment prematurely—full response may take 12+ weeks; patience in dose escalation is crucial 1
• Do not escalate doses too quickly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting therapeutic window 1
• Do not use benzodiazepines for long-term management—they lack antidepressant efficacy for comorbid depression and carry significant risks 3, 1, 4, 5, 6
• Do not forget to screen for comorbid depression—present in many GAD patients and influences treatment selection 4, 5, 6
• Review all current medications for potential interactions, particularly with CYP450 substrates, before initiating SSRIs/SNRIs 3