What are the first‑line pharmacologic treatments, with typical starting doses, for panic disorder and generalized anxiety disorder in adults?

First-Line Pharmacologic Treatment for Panic Disorder and Generalized Anxiety Disorder

Start with escitalopram 10 mg once daily or sertraline 25–50 mg once daily as your first-line medication for both panic disorder and generalized anxiety disorder in adults. 1, 2, 3

Preferred First-Line SSRIs with Starting Doses

Escitalopram

• Starting dose: 10 mg once daily (morning or evening, with or without food) 3
• Titration: May increase to 20 mg daily after a minimum of 1 week if needed 3
• Advantages: Lowest potential for drug-drug interactions and minimal discontinuation symptoms compared to other SSRIs 1

Sertraline

• Starting dose for panic disorder: 25 mg once daily 4
• After one week, increase to 50 mg once daily 4
• Starting dose for GAD: 50 mg once daily 4
• Titration: Increase by 25–50 mg increments every 1–2 weeks as tolerated, targeting 50–200 mg/day 1, 4
• Advantages: Well-established efficacy with favorable side-effect profile 1

Alternative First-Line SNRIs

Venlafaxine Extended-Release

• Starting dose: 75 mg once daily 1, 5
• Target range: 75–225 mg/day 1, 5
• Critical monitoring: Check blood pressure at baseline and regularly during treatment due to dose-dependent risk of sustained hypertension 1, 5
• Use when: SSRIs are ineffective, not tolerated, or patient has comorbid pain conditions 1

Duloxetine

• Dose: 60–120 mg/day 1
• Starting strategy: Begin at 30 mg daily for one week to reduce nausea, then increase to 60 mg 1
• Additional benefit: Particularly useful for patients with comorbid pain conditions 1

Expected Timeline for Response

• Week 2: Statistically significant improvement may begin 1, 6
• Week 6: Clinically meaningful improvement expected 1, 6
• Week 12 or later: Maximal therapeutic benefit achieved 1, 6
• Do not abandon treatment prematurely—full response requires patience and adequate trial duration 1

Common Side Effects to Anticipate

• Most frequent: Nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, dizziness, somnolence 1
• Timing: Most adverse effects emerge within the first few weeks and typically resolve with continued treatment 1
• Nausea management: This is the most common reason for discontinuation; counsel patients about early onset and expected resolution to improve adherence 1

Critical Safety Monitoring

• Suicidal ideation: All SSRIs/SNRIs carry a boxed warning for suicidal thoughts and behaviors, with pooled absolute rates of 1% versus 0.2% for placebo 1
• Monitor closely: Especially during the first months and following any dose adjustments 1
• Use standardized scales: Assess response using GAD-7 or HAM-A at every session 1

Second-Tier SSRI Options (Reserve for Later)

Paroxetine and fluvoxamine are equally effective but should be reserved for when first-tier SSRIs fail due to:

• Higher rates of discontinuation symptoms 1, 2
• Greater potential for drug-drug interactions 1, 2

Medications to Avoid

Benzodiazepines

• Not recommended for first-line or long-term therapy due to risks of dependence, tolerance, cognitive impairment, and withdrawal 1, 7
• Reserve only for short-term use (days to a few weeks) in severe acute distress 1

Beta-Blockers

• Atenolol and propranolol are deprecated for GAD and social anxiety disorder based on negative evidence 1, 2

Tricyclic Antidepressants

• Avoid due to unfavorable risk-benefit profile, particularly cardiac toxicity 1, 2

Combination with Cognitive-Behavioral Therapy

• Combined SSRI/SNRI + individual CBT provides superior outcomes compared to either treatment alone for moderate to severe anxiety 1, 7
• Individual CBT is preferred over group therapy due to superior clinical and cost-effectiveness 1
• Typical duration: 12–20 sessions over 3–4 months 1

Treatment Duration After Remission

• First episode: Continue medication for at least 9–12 months after achieving remission to prevent relapse 1, 6
• Recurrent episodes: Consider longer-term or indefinite treatment 1
• Discontinuation: Taper gradually over 10–14 days or longer to minimize withdrawal symptoms, particularly with shorter half-life SSRIs 1, 5

When to Switch Medications

• After 8–12 weeks at therapeutic doses with inadequate response, switch to a different SSRI or add CBT if not already implemented 1, 8
• Switching strategy: Cross-taper by reducing the first SSRI by 25–50 mg every 1–2 weeks while simultaneously starting the new agent at a low dose 1
• Approximately 25% of patients achieve remission after switching from one SSRI to another 1

Clinical Pitfalls to Avoid

• Do not escalate doses too quickly: Allow 1–2 weeks between increases to assess tolerability, as response follows a logarithmic model with diminishing returns at higher doses 1, 5
• Do not exceed maximum recommended doses: Escitalopram ≤20 mg/day, sertraline ≤200 mg/day, paroxetine ≤60 mg/day to minimize side effects 1, 4, 3
• Do not overlook functional impairment: Significant daily-life disruption may justify treatment even with mild symptom scores 1
• Do not commence pharmacotherapy before trialing CBT when feasible, as psychotherapy provides more durable benefits 1