A 32-year-old woman presents with recurrent, unexpected panic attacks characterized by sudden onset of palpitations, sweating, tremor, and fear of dying. She has developed anticipatory anxiety and avoidance of public places. Which is the drug of choice for long-term management of panic disorder?

Explanation

## First-Line Pharmacotherapy for Panic Disorder **Key Point:** SSRIs (selective serotonin reuptake inhibitors) are the gold standard first-line agents for panic disorder, with sertraline, paroxetine, and citalopram having the strongest evidence base. ### Rationale for Sertraline Sertraline is preferred because: 1. **Efficacy**: Reduces panic attack frequency by 50–60% and prevents anticipatory anxiety 2. **Safety profile**: Well-tolerated with minimal dependence risk 3. **Onset**: Takes 2–4 weeks for therapeutic effect (requires patient counseling) 4. **Long-term use**: Safe for chronic management without tolerance or withdrawal complications ### Mechanism in Panic Disorder SSRIs increase serotonergic neurotransmission in the amygdala and prefrontal cortex, reducing hyperarousal and threat sensitivity. This addresses the neurobiological basis of panic (dysregulated fear circuitry). ### Comparative Drug Profile | Agent | Class | Role in Panic Disorder | Limitations | |-------|-------|------------------------|-------------| | Sertraline | SSRI | **First-line** | Delayed onset (2–4 weeks) | | Paroxetine | SSRI | First-line alternative | Higher discontinuation syndrome | | Citalopram | SSRI | First-line alternative | QT prolongation at high doses | | Alprazolam | Benzodiazepine | Acute symptom relief only | Dependence, tolerance, rebound anxiety | | Buspirone | Azapirone | Adjunctive only | Ineffective monotherapy for panic | | Propranolol | β-blocker | Somatic symptom relief only | Does not prevent panic attacks | **High-Yield:** SSRIs are superior to benzodiazepines for panic disorder because they treat the underlying condition rather than masking symptoms, and carry no risk of dependence or tolerance. **Clinical Pearl:** Initial worsening of anxiety in the first 1–2 weeks is common with SSRIs in panic disorder; patients must be counseled to persist, and a short course of benzodiazepine (e.g., lorazepam) may be co-prescribed during this window. **Mnemonic:** **SSRI-PAC** = SSRIs are the Preferred Agent for Chronic panic disorder management. [cite:Harrison 21e Ch 387]