Psychiatry/Behavioral · PANCE / PANRE

Panic Disorder

Recurrent unexpected panic attacks plus >=1 month of worry about future attacks or maladaptive behavior change.

Also known as: panic attacks, panic disorder, agoraphobia

Overview

Recurrent, unexpected panic attacks — abrupt surges of intense fear or discomfort peaking within minutes — followed by >=1 month of persistent concern about additional attacks, worry about their consequences, or significant maladaptive behavior change.

Epidemiology

Lifetime prevalence ~3-5%. Female-to-male ratio ~2:1. Bimodal onset: late adolescence/early adulthood and mid-30s. ~30-50% develop agoraphobia.

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Risk factors

  • Female sex, family history of panic or anxiety disorders
  • Smoking, asthma, mitral valve prolapse (modest association)
  • Childhood adversity, recent stressful life events
  • Caffeine and stimulant use, cannabis

Pathophysiology

Hypersensitive 'fear network' centered on the amygdala with augmented locus coeruleus noradrenergic output; abnormal CO2/lactate sensitivity producing 'false suffocation alarms.' Genetic heritability ~40%.

Clinical presentation

Symptoms

  • Panic attack: >=4 of 13 symptoms peaking within minutes — palpitations, sweating, trembling, dyspnea, choking sensation, chest pain, nausea, dizziness, chills/heat, paresthesias, derealization/depersonalization, fear of losing control, fear of dying
  • Attacks last 10-30 minutes; afterwards, patients feel exhausted
  • Anticipatory anxiety between attacks and avoidance of perceived triggers
  • Agoraphobia: fear/avoidance of >=2 of: public transportation, open spaces, enclosed spaces, lines/crowds, being outside the home alone

Signs / physical exam

  • During attack: tachycardia, tachypnea, diaphoresis, mild HTN, tremor, hyperventilation
  • Between attacks: typically normal exam

Differential diagnosis

  • Cardiac (ACS, arrhythmia, SVT) — Exertional trigger, abnormal ECG/troponin, persistent symptoms — must exclude in first presentations
  • Pulmonary embolism — Hypoxia, tachycardia, pleuritic pain, risk factors; D-dimer, CTPA
  • Hyperthyroidism / pheochromocytoma — Sustained tachycardia, weight loss, paroxysmal HTN, suppressed TSH or elevated metanephrines
  • Hypoglycemia — Diaphoresis, tremor, confusion; documented low glucose
  • Vestibular dysfunction — Vertigo with positional change; nystagmus on exam
  • Substance intoxication/withdrawal — Cocaine, methamphetamine, cannabis, alcohol/benzo withdrawal
  • GAD — Chronic worry without discrete attacks
  • PTSD — Trauma cue triggers; intrusive memories

Diagnostic workup

Diagnostic criteria

DSM-5-TR: Recurrent unexpected panic attacks AND >=1 month of one or both: (a) persistent concern about additional attacks or their consequences, (b) significant maladaptive change in behavior related to attacks. Not attributable to substance/medical condition and not better explained by another disorder. Agoraphobia is a separate, often co-occurring diagnosis.

Labs

  • Targeted to exclude medical mimics: ECG, troponin (if cardiac risk), TSH, BMP, glucose, urine drug screen, urine metanephrines (paroxysmal HTN)

Imaging

  • Not routinely required; CT/CTA only if PE, dissection, or other organic cause suspected

Diagnostic algorithm

flowchart TD
  A[Recurrent abrupt fear surges<br/>peak <10 min] --> B[Exclude medical mimics<br/>ECG / TSH / glucose / UDS]
  B --> C{>=4 panic symptoms?}
  C -->|Yes| D[Panic attack]
  D --> E{>=1 month worry<br/>or behavior change?}
  E -->|Yes| F[Panic Disorder]
  E -->|No| G[Isolated panic attacks]
  F --> H[CBT with exposure +/- SSRI/SNRI]
  F --> I[Short-term benzo bridge<br/>if severe]
Panic disorder diagnostic and treatment algorithm.

Treatment

First-line

  • Cognitive behavioral therapy with interoceptive and in vivo exposure — strongest evidence base
  • SSRI — sertraline, escitalopram, paroxetine, fluoxetine (start at low dose to avoid initial activation)
  • SNRI — venlafaxine XR
  • Patient education: panic attacks are time-limited, not dangerous; reduce safety behaviors

Second-line / adjunct

  • Benzodiazepine (clonazepam, lorazepam, alprazolam) — short-term bridge for severe early symptoms; avoid as long-term monotherapy due to dependence and rebound anxiety; absolutely avoid in SUD
  • Tricyclic antidepressants (imipramine, clomipramine) — effective but anticholinergic and overdose-toxic
  • MAOIs reserved for refractory cases
  • Adjunctive lifestyle: limit caffeine/stimulants, cardiovascular exercise, sleep regularization

Complications

  • Agoraphobia and functional restriction
  • Comorbid depression, GAD, alcohol/sedative misuse
  • Suicide risk increased relative to non-anxious controls
  • Repeated ED visits and unnecessary cardiac workups

PANCE pearls

  • Panic attacks peaking >10 minutes or with focal neurologic signs are atypical — broaden the differential.
  • Alprazolam has the highest dependence and rebound risk; if benzodiazepines are used, clonazepam (longer half-life) is preferred.
  • Cognitive model: catastrophic misinterpretation of benign bodily sensations drives the panic cycle — interoceptive exposure breaks the association.
  • Continue SSRI for >=12 months after remission to reduce relapse.

References

  • APA 2009 — American Psychiatric Association Practice Guideline for the Treatment of Patients with Panic Disorder, 2nd ed. (2009)
  • NICE CG113 — NICE Clinical Guideline 113: Generalised anxiety disorder and panic disorder in adults
  • DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)

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