ICD-116B01	PANIC DISORDER Panic disorder
ICD-10F41.0	Panic disorder [episodic paroxysmal anxiety]
DSM-5-TRF41.0	Panic Disorder

1. Definition and nosology

Panic disorder (ICD-11: 6B01; DSM-5-TR: F41.0) — a disorder characterized by recurrent, unexpected panic attacks (acute episodes of fear or anxiety peaking within 10 minutes) and persistent worry about recurrence of these attacks, with behavioral changes.

2. History

• Da Costa J.M. (1871) ‘irritable heart’ — in American Civil War soldiers.
• Freud (1894) “anxiety neurosis”.
• Klein D.F. (1964) — distinguishing antidepressant response of panic attacks; basis for splitting ‘anxiety neurosis’.
• DSM-III (1980) — Official diagnosis of Panic Disorder.
• DSM-5 (2013), ICD-11 — Agoraphobia is a separate category from panic disorder.

3. Epidemiology

• Lifetime prevalence: 2–5%; annual ~2.7% (Kessler R.C. WMH).
• Sex: 2 times higher in females.
• Onset: young to middle adulthood (20–30 years); second peak in middle age.
• Comorbidity: agoraphobia 30–50%, MDD 50–60%, other anxiety disorders, substance use, mitral valve prolapse.

4. Aetiology and pathogenesis

• Heritability ~40% (Hettema 2001 meta-analysis).
• Neurobiological — amygdala-locus coeruleus-prefrontal circuit hyperreactivity; serotonergic, noradrenergic, GABAergic dysregulation.
• CO₂ sensitivity hypothesis (Klein D.F. ‘suffocation false alarm’) — patients show sensitivity to hyperventilation and CO₂ accumulation.
• Personality - anxiety sensitivity (Reiss S.); childhood history of separation anxiety.

5. Clinical features

Panic attack — 4+ symptoms peak within 10 minutes

• Palpitations, fluttering, tachycardia.
• Cold sweat, trembling.
• Shortness of breath, feeling of air insufficiency.
• Feeling of suffocation.
• Chest pain or discomfort.
• Nausea, abdominal discomfort.
• Dizziness, unreal feeling.
• Cold or hot sensations; paresthesia.
• Derealization, depersonalization.
• Fear of loss of control or “going crazy.”
• Fear of death.

Attack lasts 5–20 minutes; hospital admission is frequent (with cardiac complaints).

6. Diagnosis

6.1 Unified diagnostic criteria

A. Repeated unexpected panic attacks.

B. At least one month after at least one attack of the following:

• Persistent worry about next attack;
• Fear of consequences of attacks (heart attack, going crazy);
• Significant behavioral change associated with attacks (avoidance, safety behaviors).

C. Exclusion of substance or medical condition.

D. Not better explained by another mental disorder (social anxiety, OCD, PTSD, separation).

6.2 Source-specific clarifications

• DSM-5-TR — agoraphobia as a separate diagnosis (F40.00); may co-occur.
• ICD-11 — agoraphobia has its own code 6B02; but no one-month period of concern is required — “persistent concern” is enough.
• NICE CG113 — diagnosis after exclusion of somatic cause.

6.3 Diagnostic algorithm

1. Clinical interview + attack history.
2. SCID-5, MINI.
3. PDSS (Panic Disorder Severity Scale), GAD-7 comorbidity.
4. Medical: EKG, TSH, complete blood count, glucose, caffeine/stimulants; pheochromocytoma suspicion — 24-hour urinary metanephrines.
5. Comorbidity (agoraphobia, MDD, substance use).

6.4 Differential diagnosis

7. Examination and assessment

• PDSS, ACQ (Agoraphobic Cognitions), BSQ (Body Sensations Questionnaire).
• EKG, TSH, complete blood count, glucose.
• Holter EKG (suspected arrhythmia).
• Toxicology.

8. Treatment

8.1 General principles (NICE CG113 · CANMAT 2014)

1. CBT for panic — psychoeducation, interoceptive exposure (building tolerance to bodily sensations), in vivo exposure (to avoided situations), cognitive restructuring. 12–16 sessions. Evidence: Cuijpers P. et al. reviews — large effect.
2. Pharmacotherapy: SSRIs (sertraline, paroxetine, fluoxetine — FDA-approved for panic disorder; escitalopram off-label) or SNRIs (venlafaxine) — first-line. Start at low dose (jittery, ‘activation’ effect may worsen panic).
3. Benzodiazepine (clonazepam, lorazepam) — short-term initial stabilization; ≤ 4 weeks; dependence potential.
4. Treatment duration — ≥ 12 months after remission.
5. Caffeine, alcohol, marijuana restriction.

8.2 Source-specific clarifications

• NICE CG113 — CBT and SSRIs first-line; benzodiazepines only short-term.
• APA Anxiety Guidelines — CBT and pharmacotherapy equally effective.
• Mitte K. J Affect Disord 2005 meta-analysis — CBT superior to placebo and wait-list.

Treatment methods

1. CBT for panic — Clark (Clark D.M.), Barlow (Barlow D.H.) — Interoceptive exposure (deliberately creating body sensation — hyperventilation, spinning, caffeine) + in vivo exposure + cognitive restructuring. Evidence: Barlow D.H. et al. JAMA 2000 RCT.
2. Panic Control Treatment (PCT) — Barlow (Barlow D.H.) — 11-session manually administered protocol; widely used in the USA.
3. Panic Disorder Severity Scale (PDSS) — Shear (Shear M.K.) — 7 items; baseline indicators and monitoring.
4. Internet-based cognitive behavioral therapy (iCBT) — Andersson G. et al. demonstrated that internet-based CBT — iCBT — showed comparable efficacy to individual CBT.

9. Prognosis

• Remission with treatment in most patients.
• Comorbid agoraphobia or MDD poor prognosis.
• Early intervention prevents crystallization of avoidance behavior.

10. Myths and misconceptions

Myth 1: “Panic attack is a heart attack”

Evidence: symptoms may be similar; but panic attack is short-term, normal EKG after clinical presentation. Klein's ‘suffocation false alarm’ hypothesis explains the mechanism.

Myth 2: “The patient can voluntarily control panic”

Evidence: Panic is a neurobiological dysregulation; CBT and pharmacotherapy are required.

Myth 3: “Benzodiazepine is the main treatment for panic”

Evidence: For short-term stabilization; addiction potential; SSRIs and CBT first-line.

Myth 4: “A panic patient must be protected from panic-inducing situations”

Evidence: Avoidance strengthens the symptoms; exposure is the main therapeutic mechanism.

Myth 5: “Herbal preparations (kava, valerian) are safe for panic”

Evidence: Kava hepatotoxicity (FDA warning); standard treatment superior.

11. Sources

1. WHO. ICD-11. 6B01 Panic disorder. 2024.
2. APA. DSM-5-TR. 2022.
3. NICE CG113. 2011/2020.
4. Katzman M.A. et al. CANMAT 2014. BMC Psychiatry 2014;14(Suppl 1):S1.
5. Barlow D.H. et al. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder. JAMA 2000;283(19):2529–2536.
6. Shear M.K. et al. Multicenter collaborative panic disorder severity scale. Am J Psychiatry 1997;154(11):1571–1575.
7. Klein D.F. False suffocation alarms, spontaneous panics, and related conditions. Arch Gen Psychiatry 1993;50(4):306–317.
8. Clark D.M. A cognitive approach to panic. Behav Res Ther 1986;24(4):461–470.
9. Andersson G., Cuijpers P., Carlbring P. et al. Guided internet-based vs. face-to-face cognitive behaviour therapy for psychiatric and somatic disorders: a systematic review and meta-analysis. World Psychiatry 2014;13(3):288–295.
10. Reiss S., Peterson R.A., Gursky D.M., McNally R.J. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther 1986;24(1):1–8.
11. Kessler R.C., Berglund P., Demler O. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6):593–602.