panic disorders

**Definition (DSM-5-TR):** Recurrent unexpected panic attacks, with at least one attack followed by ≥1 month of (a) persistent concern/worry about additional attacks or their consequences (e.g., "going crazy," heart attack) and/or (b) significant maladaptive behavior change (avoiding exercise, unfamiliar places). Not attributable to substances (caffeine, stimulants, cocaine) or a medical condition, and not better explained by another mental disorder.

**Panic attack:** Abrupt surge of intense fear/discomfort peaking within ~10 minutes, with ≥4 of: palpitations/tachycardia, sweating, trembling, shortness of breath, choking sensation, chest pain, nausea/abdominal distress, dizziness/lightheadedness, chills/heat sensations, paresthesias, derealization/depersonalization, fear of losing control/"going crazy," fear of dying. Attacks usually last 20–30 minutes.

**Epidemiology:** Lifetime prevalence ~2–5%. Female:male about 2:1. Onset typically late adolescence to mid-30s. Common comorbidities: agoraphobia (about one-third or more of patients), major depression, other anxiety disorders, substance use. Increased suicide risk, especially with comorbid depression.

**Pathophysiology:** - Dysregulation of the fear network (amygdala, hypothalamus, periaqueductal gray, prefrontal cortex). - Locus coeruleus (norepinephrine) hyperactivity; decreased GABA-A and serotonin (5-HT) function. - Hypersensitive brainstem CO₂ chemoreceptors ("false suffocation alarm"). Panic can be provoked by CO₂ inhalation, sodium lactate infusion, or caffeine. - Genetic component (first-degree relatives have higher risk).

**Diagnosis:** Clinical. Rule out organic causes before diagnosing: hyperthyroidism, pheochromocytoma, arrhythmias, MI/PE, asthma/COPD, hypoglycemia, substance intoxication or withdrawal (alcohol, benzodiazepines), and medications (stimulants, albuterol). Workup commonly includes ECG, TSH, glucose, and a drug screen as indicated.

**Management:** - **First-line long-term:** SSRIs (sertraline, paroxetine, fluoxetine) or SNRIs (venlafaxine), plus/or **cognitive behavioral therapy** (interoceptive exposure, cognitive restructuring). CBT has the most durable benefit and a lower relapse rate. Start SSRIs at low doses, because initial jitteriness can transiently worsen anxiety. Benefit takes 4–6 weeks. - **Second-line:** TCAs (imipramine, clomipramine), MAOIs. - **Benzodiazepines** (alprazolam, clonazepam): rapid relief, used short-term or as a bridge until SSRIs take effect. Risks include dependence, tolerance, withdrawal seizures, and sedation. Avoid in patients with substance use disorder. - **Propranolol/β-blockers:** Not effective for panic disorder. They help performance anxiety (a social anxiety subtype).

**High-yield distinctions:** - **Panic attack vs. panic disorder:** A panic attack is a symptom and can occur in many disorders (PTSD, phobias, depression). Panic disorder requires recurrent *unexpected* attacks plus persistent worry or behavior change. - **Specific/social phobia:** Attacks are cued by a particular stimulus, not unexpected. - **GAD:** Chronic, diffuse worry for ≥6 months without discrete abrupt attacks. - **Agoraphobia:** Fear of situations where escape would be difficult (public transit, crowds, open or enclosed spaces). Diagnosed separately in DSM-5 even when it co-occurs with panic disorder. - **Hyperthyroidism/pheochromocytoma:** Consider these when symptoms are persistent or paroxysmal with hypertension, headache, or weight loss.

**Board pearl:** A young woman with episodes of palpitations, chest tightness, and fear of dying, with a normal ECG and workup, who now avoids leaving home, has panic disorder with agoraphobia. Start an SSRI and CBT.