What is the first-line treatment for generalized anxiety disorder in adults?

First-Line Treatment for Anxiety in Adults

Selective serotonin reuptake inhibitors (SSRIs)—specifically escitalopram or sertraline—are the first-line pharmacological treatment for generalized anxiety disorder in adults, with cognitive behavioral therapy (CBT) equally effective and often combined for superior outcomes. 1

Primary Treatment Options

Pharmacotherapy: SSRIs as First-Line Agents

• Escitalopram (10–20 mg daily) and sertraline (50–200 mg daily) are the preferred initial medications due to their established efficacy, favorable safety profiles, and lowest risk of discontinuation symptoms compared to other SSRIs. 1

• Start escitalopram at 10 mg once daily, increasing to 20 mg after a minimum of one week if needed. 2

• Start sertraline at 25–50 mg daily, titrating by 25–50 mg increments every 1–2 weeks as tolerated, targeting 50–200 mg/day. 1

• Expect a logarithmic response pattern: statistically significant improvement by week 2, clinically meaningful improvement by week 6, and maximal benefit by week 12 or later. 1

Alternative First-Line: SNRIs

• Venlafaxine extended-release (75–225 mg/day) or duloxetine (60–120 mg/day) are effective alternatives when SSRIs are ineffective, not tolerated, or when comorbid pain conditions exist. 1

• Venlafaxine requires blood pressure monitoring due to risk of sustained hypertension. 1

• Duloxetine nausea can be reduced by starting at 30 mg daily for one week before increasing. 1

Psychotherapy: Cognitive Behavioral Therapy

• Individual CBT (12–20 sessions) demonstrates large effect sizes (Hedges g = 1.01) for generalized anxiety disorder and is prioritized over group therapy due to superior clinical and cost-effectiveness. 1

• CBT should include education on anxiety, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate. 1

• When face-to-face CBT is unavailable, self-help CBT with professional support is a viable alternative. 1

Combined Treatment Approach

• Combining an SSRI or SNRI with individual CBT provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety. 1

• This combination strategy is supported by moderate-to-high strength evidence across multiple anxiety disorder subtypes. 1

Second-Line Medications

• Paroxetine and fluvoxamine are equally effective SSRIs but reserved as second-tier options due to higher discontinuation symptoms and greater drug interaction potential. 1

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

Common Side Effects to Monitor

• Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, heartburn, somnolence, dizziness, and vivid dreams typically emerge within the first few weeks. 1

• Most adverse effects resolve with continued treatment; gradual dose escalation minimizes initial anxiety or agitation. 1

• Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments (pooled risk 1% vs 0.2% placebo; NNH = 143). 1

Treatment Duration and Maintenance

• Continue effective medication for a minimum of 9–12 months after achieving remission to prevent relapse. 1

• Reassess monthly until symptoms stabilize, then every 3 months using standardized scales (GAD-7 or HAM-A). 1

• Discontinue medication gradually over 10–14 days to avoid withdrawal syndrome (dizziness, paresthesias, anxiety, irritability), particularly with shorter half-life SSRIs. 1

Medications to Avoid

• Benzodiazepines should be reserved for short-term use only (days to a few weeks) due to risks of dependence, tolerance, cognitive impairment, and withdrawal. 1

• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity. 1

• Beta-blockers (atenolol, propranolol) are deprecated for generalized anxiety disorder based on negative evidence. 1

Adjunctive Non-Pharmacological Strategies

• Structured physical activity and regular cardiovascular exercise provide moderate to large reductions in anxiety symptoms. 1

• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, and mindfulness are useful adjunctive strategies. 1

• Avoid excessive caffeine and alcohol, as both can exacerbate anxiety symptoms. 1

• Sleep hygiene education addresses insomnia, which commonly co-occurs with anxiety. 1

Algorithm for Treatment Failure

• If inadequate response after 8–12 weeks at therapeutic doses despite good adherence, switch to a different SSRI or SNRI, or add individual CBT if not already implemented. 1

• Approximately 25% of patients achieve symptom remission after switching from one SSRI to another. 1

• Before declaring treatment failure, confirm the patient received a full 8–12 week course at therapeutic doses. 1

Critical Pitfalls to Avoid

• Do not escalate doses too quickly—allow 1–2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 1

• Do not abandon treatment prematurely—full response may take 12+ weeks, and patience in dose escalation is crucial for optimal outcomes. 1

• Patients with anxiety pathology commonly avoid follow-through on referrals; proactively assess and address barriers to treatment adherence. 1

• Screen for bipolar disorder, mania, or hypomania before initiating antidepressant treatment. 2