## First-Line Pharmacotherapy for Panic Disorder **Key Point:** SSRIs (selective serotonin reuptake inhibitors) are the gold standard first-line agents for long-term management of panic disorder, with sertraline being the most extensively studied and recommended. ### Mechanism SSRIs increase synaptic serotonin by blocking reuptake at the presynaptic terminal, modulating amygdala reactivity and reducing panic threshold over 2–4 weeks of treatment. ### Evidence Base Sertraline has FDA approval for panic disorder and demonstrates: - Efficacy in reducing panic attack frequency and severity - Prevention of relapse with sustained use - Good tolerability and safety profile - Onset of action: 2–4 weeks (full effect by 8–12 weeks) ### Dosing in Panic Disorder - **Starting dose:** 25–50 mg daily - **Target dose:** 50–100 mg daily - **Maximum dose:** 200 mg daily **High-Yield:** Other SSRIs (paroxetine, fluoxetine, citalopram) and SNRIs (venlafaxine) are also first-line, but sertraline is most commonly tested and recommended in Indian guidelines. ### Why SSRIs Over Other Classes | Feature | SSRI | Benzodiazepine | Beta-blocker | Buspirone | |---------|------|-----------------|--------------|----------| | **Efficacy** | Excellent | Good (acute) | Poor | Minimal | | **Dependence risk** | None | High | None | None | | **Long-term use** | Ideal | Contraindicated | Limited | Ineffective | | **Onset** | 2–4 weeks | Minutes | Hours | 2–4 weeks | | **Relapse prevention** | Yes | No | No | No | **Clinical Pearl:** Benzodiazepines provide rapid symptom relief but are reserved for acute distress or short-term bridging (first 2 weeks) because of addiction potential and paradoxical worsening of anticipatory anxiety with chronic use. **Mnemonic:** **SSRI-FIRST** — SSRIs are First-line In Recurrent Situational Tension; Ideal for Relapse prevention; Recommended for Sustained Treatment. [cite:Harrison 21e Ch 397]
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