Panic attacks

A panic attack is an abrupt surge of intense fear or discomfort that reaches a peak within minutes and is accompanied by a cluster of somatic and cognitive symptoms. It is a symptom pattern, not a diagnosis.

Definition of a panic attack.

An abrupt surge of fear or discomfort that peaks within minutes (usually within 10 minutes, with most attacks lasting 5 to 30 minutes), with 4 or more of the following:

• palpitations or pounding heart
• sweating
• trembling or shaking
• shortness of breath or a sense of smothering
• a choking sensation
• chest pain or discomfort
• nausea or abdominal distress
• dizziness or light headedness
• chills or heat sensations
• numbness or tingling
• derealisation or depersonalisation
• fear of losing control or of going mad
• fear of dying

Attacks with fewer than 4 symptoms are limited symptom attacks.

Definition of panic disorder. Recurrent unexpected panic attacks, with at least one attack followed by 1 month or more of:

• persistent concern about further attacks or their consequences (for example fear of a heart attack or of losing control); or
• a maladaptive change in behaviour related to the attacks (avoidance of exercise or unfamiliar places).

The disturbance is not caused by a substance or a medical condition and is not better explained by another mental disorder.

Classification. Expected (cue bound) attacks are triggered by a recognised fear stimulus, such as phobia or social anxiety. Unexpected (uncued) attacks arise without an obvious trigger and are required for panic disorder. Nocturnal attacks wake the patient from non-REM sleep with sudden fear and autonomic arousal, without the dream content of a nightmare.

Panic disorder may occur with or without agoraphobia, which is fear and avoidance of at least 2 situations such as public transport, open spaces, enclosed places, queues or crowds, or being outside home alone, because escape might be difficult.

Panic attacks may also be a specifier of depression, bipolar disorder, posttraumatic stress disorder and substance use disorders. Medical and substance induced panic attacks form a separate group.

Epidemiology. About 1 in 10 adults has a panic attack in a year. Panic disorder has a lifetime prevalence of 2 to 5%, is twice as common in women, and commonly begins between late adolescence and the mid 30s. First degree relatives carry a higher risk. Patients with panic disorder attend emergency departments and cardiology clinics repeatedly before diagnosis.

Mechanisms.

• Heightened sensitivity to carbon dioxide and to bodily sensations.
• Hyperventilation with hypocapnia and respiratory alkalosis (which lowers ionised calcium and produces perioral and limb paraesthesia and carpopedal spasm).
• Amygdala hyperreactivity with reduced prefrontal control.
• Noradrenergic overactivity in the locus coeruleus.
• Altered serotonin and gamma aminobutyric acid signalling.
• Conditioned fear of interoceptive cues.

A catastrophic misreading of normal sensations sustains the cycle.

Course. Without treatment, the course is chronic and relapsing, with a high rate of comorbid depression (about half of patients), alcohol and benzodiazepine misuse, and suicidal ideation. Avoidance leads to agoraphobia in many patients. With treatment, most patients improve, and relapse after stopping drugs is common unless cognitive behavioural therapy has been completed.

Key distinctions. A peak within minutes with a feeling of impending doom in a young patient with a normal examination suggests panic.

Symptoms that start with exertion, last longer than an hour, or occur with ischaemic ECG changes, hypoxia, syncope or focal neurology point to organic disease. Paraesthesia of the hands and mouth with deep breathing suggests hyperventilation.

A first attack after the age of 45 years, or an attack with weight loss, tremor, sweating and hypertension, should lead to a search for a medical cause before panic disorder is diagnosed.

History

• The attack itself: onset (sudden or building), time to peak, duration, symptoms in order, triggers, exertional or positional features, relief, and the patient's belief about what is happening (heart attack, stroke, death, loss of control).
• Frequency and pattern: number of attacks in the past month, nocturnal attacks, situational avoidance, safety behaviours (carrying medicines, staying near exits, checking pulse), and time off work or school.
• Worry between attacks, anticipatory anxiety, and the effect on driving, travel, shopping, exercise and relationships.
• Cardiac and respiratory symptoms: exertional chest pain, orthopnoea, syncope, palpitations with sudden onset and offset (arrhythmia), wheeze, pleuritic pain, leg swelling, recent immobilisation or surgery.
• Endocrine and other symptoms: weight loss, heat intolerance, tremor, episodic headache with sweating and pallor (phaeochromocytoma), flushing and diarrhoea (carcinoid), symptoms relieved by eating (hypoglycaemia), menstrual pattern and menopause, polyuria.
• Neurological symptoms: aura, olfactory or gustatory sensations, déjà vu, loss of awareness, post attack confusion (temporal lobe seizures), vertigo (vestibular disease), transient focal weakness (transient ischaemic attack).
• Substances: caffeine (cups daily), energy drinks, nicotine, alcohol (binge and withdrawal), cannabis, cocaine, amphetamines, khat, hallucinogens, opioids and benzodiazepines (use and recent stopping).
• Drugs: salbutamol, theophylline, levothyroxine, corticosteroids, pseudoephedrine, SSRIs at start, bupropion, antipsychotics (akathisia), stimulant medicines, thyroid hormone, sympathomimetic diet pills, and anticholinergics.
• Psychiatric history: depression, bipolar disorder, trauma, obsessive compulsive disorder, social anxiety, eating disorders, psychosis, previous treatment and response, and suicidal thoughts.
• Family history of panic, anxiety, depression, sudden cardiac death and thyroid disease. Childhood adversity, bereavement, current stressors, violence, and caring duties.

Examination

• Vital signs during and between attacks: heart rate and rhythm, blood pressure (both arms when pain is present), temperature, respiratory rate, oxygen saturation, and weight.
• Appearance during an attack: sweating, pallor, tremor, hyperventilation (rate over 20 breaths a minute, sighing breathing), carpopedal spasm, perioral tingling, and anxiety.
• Cardiovascular: rhythm, murmurs (mitral valve prolapse, aortic stenosis, hypertrophic cardiomyopathy), signs of heart failure, peripheral pulses, and postural blood pressure change.
• Respiratory: wheeze, reduced air entry, crackles, and signs of pneumothorax or effusion.
• Endocrine: goitre, thyroid bruit, eye signs, fine tremor, brisk reflexes, warm moist skin, cushingoid features, and hypertension.
• Neurological: cranial nerves, nystagmus, gait, focal deficit, and tongue bite or incontinence if loss of awareness was reported.
• Mental state: mood, thought content (catastrophic misinterpretation), perceptual disturbance, suicidal thoughts, and cognition.
• Bedside tests: pulse oximetry, glucose, 12 lead ECG, pregnancy test, urine drug screen if intoxication is possible, and peak flow if wheeze is present. Repeat the ECG if pain recurs.

Red flags

• Chest pain with exertion, radiation, ECG changes, raised troponin, or risk factors for ischaemic heart disease.
• Syncope, sustained palpitations, heart rate over 150 beats a minute, irregular rhythm, or ECG evidence of pre-excitation, prolonged QT, or Brugada pattern.
• Breathlessness with hypoxia, pleuritic pain, haemoptysis, leg swelling, or recent surgery or immobility (pulmonary embolism).
• Weight loss, heat intolerance, tremor and goitre (hyperthyroidism).
• Episodic severe headache, sweating, pallor and hypertension (phaeochromocytoma).
• Symptomatic hypoglycaemia in a patient on insulin, a sulphonylurea or after bariatric surgery.
• First attack after age 45 years, no personal or family history of anxiety, or atypical features such as loss of awareness.
• Focal neurological signs, new severe headache, or visual disturbance.
• Intoxication or withdrawal: alcohol, benzodiazepines, opioids, stimulants.
• Suicidal ideation, psychosis, mania, or posttraumatic stress with flashbacks.
• Pregnancy or postpartum period.
• Anaphylaxis features: urticaria, wheeze, angioedema, and hypotension after exposure.

Special groups

• Adolescents and children: somatic complaints, school refusal, and nocturnal attacks. Use age specific doses and psychological treatment first.
• Pregnancy and breastfeeding: avoid paroxetine and benzodiazepines in late pregnancy, and exclude pulmonary embolism, hyperthyroidism and anaemia.
• Older adults: new onset panic is usually medical, drug related or a sign of depression or dementia. Falls risk limits benzodiazepines.
• People with cardiac or respiratory disease: panic and organic disease coexist, and both are treated.
• Region specific: culturally shaped presentations such as ataque de nervios, khyal attacks and wind attacks, high prevalence of somatic presentation, khat use, and trauma related panic in conflict affected populations.

Psychiatric and primary anxiety disorders

• Panic disorder with or without agoraphobia.
• Generalised anxiety disorder with panic attacks.
• Social anxiety disorder and specific phobia (cued attacks).
• Posttraumatic stress disorder and acute stress disorder.
• Obsessive compulsive disorder.
• Separation anxiety disorder.
• Major depression and bipolar disorder with anxious distress or mixed features.
• Illness anxiety disorder and somatic symptom disorder.
• Psychotic disorders, including prodrome.
• Dissociative disorders and nocturnal dissociation.
• Premenstrual dysphoric disorder.

Cardiac

• Acute coronary syndrome and coronary vasospasm.
• Supraventricular tachycardia, atrial fibrillation, atrial flutter, ventricular tachycardia, and Wolff-Parkinson-White syndrome.
• Long QT syndrome and Brugada syndrome.
• Postural orthostatic tachycardia syndrome.
• Mitral valve prolapse, aortic stenosis, and hypertrophic cardiomyopathy.
• Heart failure and cardiomyopathy.
• Pericarditis and myocarditis.
• Aortic dissection.

Respiratory

• Pulmonary embolism.
• Asthma and COPD exacerbation.
• Pneumothorax.
• Hyperventilation syndrome and dysfunctional breathing.
• Hypoxia of any cause, and carbon monoxide poisoning.
• Vocal cord dysfunction.

Endocrine and metabolic

• Hyperthyroidism and thyroid storm.
• Hypoglycaemia (insulin, sulphonylureas, insulinoma, postprandial hypoglycaemia).
• Phaeochromocytoma and paraganglioma.
• Carcinoid syndrome.
• Hyperparathyroidism, hypocalcaemia and hypomagnesaemia.
• Cushing syndrome and Addison disease.
• Menopause and hormonal fluctuation.
• Anaemia, vitamin B12 deficiency and porphyria.

Neurological

• Temporal lobe epilepsy and focal seizures with fear.
• Vestibular disorders, vestibular migraine and Meniere disease.
• Transient ischaemic attack.
• Migraine aura.
• Brain tumour and limbic encephalitis.
• Sleep related: sleep apnoea, nocturnal reflux, night terrors, and REM sleep behaviour disorder.

Substance and drug related

• Caffeine intoxication.
• Cocaine, amphetamine, methamphetamine, khat and synthetic stimulant intoxication.
• Cannabis intoxication and synthetic cannabinoids.
• Hallucinogen effects.
• Alcohol, benzodiazepine, barbiturate and opioid withdrawal.
• Nicotine withdrawal.
• SSRI initiation and antidepressant discontinuation syndrome.
• Drug induced: salbutamol, theophylline, levothyroxine, corticosteroids, decongestants, bupropion, antipsychotic akathisia.
• Serotonin syndrome and anticholinergic toxicity.

Other

• Anaphylaxis.
• Sepsis and fever.
• Mastocytosis.
• Pregnancy complications.
• Malingering or factitious symptoms (rare).

Step 1. Exclude danger. Check airway, breathing and circulation, vital signs, oxygen saturation, glucose and a 12 lead ECG in every patient presenting with an attack. Treat any abnormality on its own terms.

Do not diagnose panic from a normal initial ECG when pain is exertional, prolonged or accompanied by risk factors.

Step 2. Clinical diagnosis of the attack and the disorder. Confirm the symptom criteria (4 or more symptoms, peak within minutes), the unexpected pattern, the persistent concern or behavioural change for at least 1 month, and the exclusion of substance or medical causes.

Establish comorbid depression (PHQ-9), generalised anxiety (GAD-7), alcohol (AUDIT-C), trauma, obsessions and bipolar features.

Quantify severity with the Panic Disorder Severity Scale (7 items, scored 0 to 28; 8 or more is clinically significant) and the Anxiety Sensitivity Index, and record attacks in a diary.

Step 3. First line tests

• 12 lead ECG for rhythm, pre-excitation (short PR, delta wave), QT interval, Brugada pattern, ischaemia and left ventricular hypertrophy.
• Capillary glucose and, in recurrent attacks, HbA1c.
• Full blood count, urea, creatinine, electrolytes, calcium (corrected for albumin), magnesium, and liver tests.
• Thyroid stimulating hormone, with free thyroxine when abnormal.
• Pregnancy test in women of reproductive age.
• Urine or serum drug screen when intoxication or withdrawal is possible, and blood alcohol when relevant.
• Troponin (high sensitivity, repeated at 1 to 3 hours depending on the assay) when chest pain is present.

Step 4. Targeted tests

• Palpitations: 24 to 72 hour ambulatory ECG, 7 to 14 day patch monitoring, or an event recorder for infrequent episodes, plus echocardiography.
• Exertional symptoms or risk factors: exercise ECG, CT coronary angiography or functional imaging.
• Syncope with panic features: tilt table testing and orthostatic vital signs (heart rate rise of 30 beats a minute or more within 10 minutes of standing without orthostatic hypotension suggests postural orthostatic tachycardia syndrome).
• Pulmonary embolism: pretest probability by a validated score (Wells), D-dimer when probability is low or moderate (age adjusted threshold of age multiplied by 10 micrograms/L in patients over 50 years), and CT pulmonary angiography when positive or probability is high.
• Respiratory: peak flow, spirometry, chest radiograph, and arterial blood gas during an attack if feasible (hypocapnia with normal oxygen supports hyperventilation).
• Phaeochromocytoma: plasma free metanephrines (supine sampling) or 24 hour urinary fractionated metanephrines for episodic hypertension, pallor and sweating, with CT or MRI of the abdomen when raised more than twice the upper limit.
• Carcinoid: 24 hour urinary 5-hydroxyindoleacetic acid for flushing and diarrhoea.
• Hypoglycaemia: supervised fast or critical sample during symptoms (glucose, insulin, C-peptide, proinsulin, beta hydroxybutyrate, sulphonylurea screen).
• Neurological: electroencephalogram (sleep deprived) and MRI brain for seizure features, onset after age 40 years, or focal signs.
• Sleep study when nocturnal attacks and snoring suggest sleep apnoea.
• Cortisol, parathyroid hormone, vitamin D, B12 and ferritin when clinical features indicate.

Hyperventilation assessment. The Nijmegen questionnaire (16 items, score of 23 or more suggests hyperventilation syndrome) and the voluntary hyperventilation provocation test (reproduces symptoms) support the diagnosis but do not exclude organic disease. End tidal carbon dioxide under 4.0 kPa (30 mmHg) during an attack supports hypocapnia.

Interpretation. A normal cardiac and metabolic screen in a patient with typical attacks, a young age and a supportive history is enough to make the diagnosis, and further testing should be limited because repeated testing sustains health anxiety. Abnormal findings do not rule out panic, since panic and organic disease coexist. Explain results in a way that links symptoms to anxiety physiology.

Limits. No test confirms panic disorder. Hypocapnia is not specific. ECG and troponin at presentation can miss intermittent arrhythmias. Self report questionnaires screen but do not diagnose. Conditions such as postural orthostatic tachycardia syndrome, hyperthyroidism and phaeochromocytoma may cause panic attacks and also need their own treatment.

Immediate management of an attack

• Calm, private setting, a steady explanation that the attack is frightening but not dangerous, and a clinician who stays with the patient.
• Slow diaphragmatic breathing: inhale through the nose for 4 seconds, exhale slowly through pursed lips for 6 seconds, about 6 breaths a minute, for 5 to 10 minutes. Do not use paper bag rebreathing because it can cause hypoxia.
• Grounding: name 5 things seen, 4 heard, 3 touched. Reduce stimulation and caffeine.
• Treat reversible triggers: oxygen if saturation is under 94%, glucose if hypoglycaemia, bronchodilator if wheeze.
• Single dose benzodiazepine only for severe distress that does not settle: lorazepam 0.5 to 1 mg orally or sublingually once (1 mg orally in adults, 0.5 mg in older adults), or diazepam 2 to 5 mg orally once. Avoid repeated doses in the department and never supply repeat prescriptions from the first presentation.
• Observe for 1 to 2 hours after severe attacks and when cardiac or respiratory disease is possible. Discharge when symptoms are settled and the cardiac assessment is complete.

Psychological treatment (first line, alone for mild to moderate disease and with drugs for severe disease)

• Education about the physiology of panic, the fear cycle, and the effect of caffeine, alcohol and hyperventilation.
• Cognitive behavioural therapy, usually 12 to 16 weekly sessions, with interoceptive exposure (induced bodily sensations such as breathing through a straw, spinning, running on the spot), situational exposure for agoraphobia, and cognitive restructuring. Response rates are about 50 to 70% and benefits persist after stopping.
• Applied relaxation, supported self help and internet delivered programmes are alternatives. Regular aerobic exercise (30 minutes on most days) and sleep regularity are useful additions.

Pharmacological treatment (moderate to severe disease, comorbid depression, patient preference, or no access to psychological therapy)

• Sertraline 25 mg orally once daily for 1 week, then 50 mg daily, increased every 1 to 2 weeks to a usual 100 to 150 mg, maximum 200 mg daily. First line, with fewer interactions, and suitable in cardiac disease.
• Escitalopram 5 mg orally once daily for 1 week, then 10 mg daily, increased after 2 weeks to a maximum of 20 mg daily (10 mg daily in people over 65 years and in hepatic impairment). Monitor QT interval.
• Paroxetine 10 mg orally once daily for 1 week, then 20 mg, increased in steps of 10 mg weekly to a usual 40 mg, maximum 60 mg daily (40 mg in older adults). It has more discontinuation symptoms, weight gain and anticholinergic effects, and is avoided in pregnancy.
• Fluoxetine 10 mg orally once daily for 1 week, then 20 mg, usual 20 to 40 mg, maximum 60 mg daily. Long half life reduces discontinuation symptoms. It is a strong CYP2D6 inhibitor.
• Venlafaxine modified release 37.5 mg once daily for 1 week, then 75 mg, increased to a maximum of 225 mg daily. Monitor blood pressure and reduce the dose in kidney and hepatic impairment.
• Clomipramine 10 mg orally once daily for 1 week, increased by 10 mg weekly to a usual 30 to 75 mg, maximum 150 mg daily. Second line, with ECG, anticholinergic effects and overdose risk (limit supply).
• Start all antidepressants at the low doses stated, since early jitteriness and an increase in panic symptoms in the first 1 to 2 weeks are common and cause discontinuation. Warn the patient, and review at 1 to 2 weeks and 4 to 6 weeks.
• Benefit begins at 2 to 4 weeks, and full effect takes 8 to 12 weeks. If under 20% improvement at 4 to 6 weeks on an adequate dose, increase the dose, then switch class.
• Benzodiazepine as a bridge only, for 2 to 4 weeks while an antidepressant takes effect: clonazepam 0.25 mg orally twice daily, increased to a usual 0.5 to 2 mg daily in 2 divided doses (maximum 4 mg daily).
• Alternatively, alprazolam 0.25 to 0.5 mg three times daily (maximum 4 mg daily; short half life, higher dependence risk).
• Avoid in older adults, substance misuse, sleep apnoea, respiratory disease, pregnancy and driving. Taper by 5 to 10% of the dose every 1 to 2 weeks after prolonged use.
• Beta blockers, buspirone, hydroxyzine and antipsychotics are not effective for the disorder. Propranolol 10 to 40 mg orally treats somatic symptoms in performance anxiety only, and is avoided in asthma, heart block and diabetes with hypoglycaemia risk.

Duration. Continue an effective antidepressant for 12 months after remission, then taper over at least 4 to 8 weeks with cognitive behavioural therapy in place. Relapse after stopping is about a third without psychological treatment.

Specific causes

• Hyperthyroidism: carbimazole 15 to 40 mg orally once daily, with propranolol 10 to 40 mg three or four times daily (maximum 160 mg daily) until euthyroid.
• Supraventricular tachycardia: vagal manoeuvres, adenosine 6 mg intravenous bolus (then 12 mg and 12 mg), and cardiology referral for ablation.
• Postural orthostatic tachycardia syndrome: fluid 2 to 3 litres daily, salt 6 to 10 g daily, compression garments, graded exercise, and specialist drug therapy.
• Phaeochromocytoma: alpha blockade with phenoxybenzamine 10 mg orally twice daily increased to a maximum of 1 mg/kg daily in divided doses, or doxazosin 2 to 16 mg daily, before beta blockade and surgery.
• Hypoglycaemia: oral glucose 15 to 20 g, or glucagon 1 mg intramuscularly, and review of insulin or sulphonylurea doses.
• Alcohol and benzodiazepine withdrawal: chlordiazepoxide 15 to 30 mg orally every 6 hours reducing over 5 to 7 days, with thiamine 100 mg daily orally.
• Caffeine: cut intake gradually to under 200 mg daily (about 2 cups of coffee), stop energy drinks, and stop nicotine and stimulant use.
• Drug induced attacks: reduce the dose, change the drug, or stop it when possible.

Special populations

• Pregnancy and breastfeeding: psychological therapy first. Sertraline is preferred when a drug is needed. Avoid paroxetine and benzodiazepines in late pregnancy. Do not stop treatment abruptly.
• Adolescents: cognitive behavioural therapy first. Sertraline 25 mg once daily increasing to 50 to 100 mg, maximum 200 mg, with weekly review in the first month for suicidality.
• Older adults: sertraline 12.5 to 25 mg daily, titrated slowly, with sodium checked at 2 weeks. Avoid benzodiazepines and tricyclic antidepressants.
• Kidney and liver impairment: start at half doses and titrate slowly. Avoid duloxetine at creatinine clearance under 30 mL/min.
• Cardiac disease: sertraline is preferred. Avoid citalopram at doses over 20 mg daily and tricyclic antidepressants.

Monitoring. Panic diary (attack frequency, severity, avoidance), Panic Disorder Severity Scale every 4 weeks (a fall of 40% or more is a response), PHQ-9, adherence, adverse effects, alcohol and caffeine use, suicidality, sodium and QT where indicated, and function.

Referral and escalation. Mental health services urgently for suicidal ideation, psychosis, severe functional impairment, and substance dependence. Routine referral to psychological therapy services for all patients who have had attacks for 4 weeks or more, and to psychiatry for diagnostic uncertainty, treatment resistance, severe agoraphobia and comorbid bipolar disorder or trauma disorders.

Cardiology, endocrinology, neurology or respiratory medicine when a medical contributor is identified. Admission criteria. Suicidal intent, psychosis, severe withdrawal, diagnostic uncertainty with high risk cardiac features, and inability to care for oneself.

Discharge and follow up. Written explanation of panic, breathing exercises, and a plan for the next attack. Review in 1 to 2 weeks after starting a drug, then every 2 to 4 weeks until stable. Safety net advice: return immediately for exertional chest pain, syncope, chest pain lasting over 20 minutes, one sided weakness, severe breathlessness, persistent palpitations, thoughts of self harm, or worsening in the first weeks of an antidepressant.