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Panic Disorder
Anub G. John, MD
Yash Kothari, MD
Hugh R. Peterson, MD, FACP
image BASICS
  • A classic panic attack that is characterized by rapid onset of a brief period of sympathetic nervous system hyperarousal accompanied by intense fear.
  • In panic disorder, multiple panic attacks occur (including at least one without a recognizable trigger). Worried anticipation of additional attacks, which can be disabling, is present for at least 1 month, and often, maladaptive (e.g., avoidance) behaviors develop.
  • Predominant age: All ages; in school-aged children, panic disorder can be confused with conduct disorder and school avoidance.
  • Peak age of onset is early to mid-20s.
  • Predominant sex: female > male (2:1)
  • Lifetime prevalence: 4.7% (1)
  • 4-8% of patients in a primary care practice population have panic disorder.
  • Of patients presenting with chest pain in the emergency room, 25% have panic disorder.
  • Chest pain is more likely due to panic if atypical, younger age, female, and known problems with anxiety.
  • Biologic theories focus on limbic system malfunction in dealing with anxiety-evoking stimuli.
  • Psychological theories posit deficits in managing strong emotions such as fear and anger.
  • Noradrenergic neurotransmission from the locus coeruleus causes increased sympathetic stimulation throughout the body.
  • Current neurobiologic research focuses on abnormal responses to anxiety-producing stimuli in the hippocampus, amygdala, and prefrontal cortex; for example, there appears to be limbic kindling in which an original frightening experience dominates future responses even when subsequent exposures are not objectively threatening.
  • Brain pH disturbances (e.g., excess lactic acid) from normal mentation in genetically vulnerable patients may activate the amygdala and generate unexpected fear responses.
Twin and family studies support a genetic predisposition.
  • Life stressors of any kind can precipitate attacks.
  • History of sexual abuse and physical abuse, anxious and overprotective parents
  • Substance abuse, bipolar disorder, major depression, obsessive-compulsive disorder (OCD), and simple phobia
  • Of patients with panic disorder, >70% also have ≥1 other psychiatric diagnoses: PTSD (recalled trauma precedes panic attack), social phobia (fear of scrutiny precedes panic attack), simple phobia (fear of something specific precedes panic), major depression, bipolar disorder, substance abuse, OCD, separation anxiety disorder.
  • Panic disorder is more common in patients with asthma, migraine headaches, hypertension, mitral valve prolapse, reflux esophagitis, interstitial cystitis, irritable bowel syndrome, fibromyalgia, nicotine dependence, and suicidality.
  • Panic attack: an abrupt surge of intense fear, reaching a peak within minutes in which ≥4 of the following symptoms develop abruptly: (i) palpitations, pounding heart, or accelerated heart rate; (ii) sweating; (iii) trembling or shaking; (iv) sensations of shortness of breath or feeling smothered; (v) a choking sensation; (vi) chest pain or discomfort; (vii) nausea or abdominal distress; (viii) feeling dizzy, unsteady, lightheaded, or faint; (ix) derealization (feelings of unreality) or depersonalization (feeling detached from oneself); (x) fear of losing control or going crazy; (xi) fear of dying; (xii) paresthesias; (xiii) chills or hot flushes (2)[C]
  • Panic disorder: recurrent unexpected panic attacks not better accounted for by another psychiatric condition (e.g., PTSD, OCD, separation anxiety disorder, social anxiety disorder, or specific phobia) and not induced by drugs of abuse, medical conditions, or prescribed drugs and with >1 month of at least one of the following: (i) worry about additional attacks; (ii) worry about the implications of the attack (e.g., losing control, having a heart attack, “going crazy”); and/or (iii) a significant maladaptive change in behavior related to the attacks (2)[C]
  • Unlike DSM-IV, DSM-5 defines agoraphobia as separate from panic disorder (2)[C].
  • During an attack, there will be tachycardia, hyperventilation, and sweating.
  • Check the thyroid for fullness or nodules.
  • Cardiac exam to check for a murmur or arrhythmias
  • Lung exam to rule out asthma (limited airflow, wheezing)
  • Medication use may mimic panic disorder and create anxiety: Antidepressants to treat panic may paradoxically initially cause panic; antidepressants in bipolar patients can cause anxiety/mania/panic; short-acting benzodiazepines (alprazolam), &bgr;-blockers (propranolol), and short-acting opioids can cause interdose rebound anxiety; benzodiazepine treatment causes panic when patients take too much and run out of these medicines early; bupropion, levodopa, amphetamines, steroids, albuterol, sympathomimetics, fluoroquinolones, and interferon can cause panic.
  • Substances of abuse: alcohol withdrawal, benzodiazepine withdrawal, opioid withdrawal, caffeine, marijuana (panic with paranoia), amphetamine abuse, MDMA, hallucinogens (PCP, LSD), dextromethorphan abuse, synthetic cathinones (bath salts) abuse.
  • Medical conditions: hypo-/hyperthyroidism, asthma/chronic obstructive pulmonary disease (COPD), reflux esophagitis with hyperventilation, tachyarrhythmias, premenstrual dysphoric disorder, menopause, pregnancy, hypoglycemia (in diabetes), hypoxia, inner ear disturbances (labyrinthitis), myocardial infarction, pulmonary embolus, transient ischemic attacks (TIAs), carcinoid syndrome, pre- and postictal states (e.g., in TLE), autoimmune disease, pheochromocytoma, Cushing syndrome, hyperaldosteronism, Wilson disease
  • Psychiatric conditions that have overlapping symptomatology include mood, anxiety, and personality disorders such as major depression, bipolar disorder, PTSD, borderline personality disorder, social phobia, OCD, and generalized anxiety disorder. In PTSD, there is always a recollection or visual image that precedes the panic attack. In social phobia, fear of scrutiny precedes the panic attack. In bipolar disorder, major depression, borderline personality disorder, and particularly substance abuse, the patient often complains first of panic symptoms and anxiety and minimizes other potentially relevant symptoms and behaviors.
  • Somatic symptom disorder is also an illness of multiple unexplained medical symptoms, but the presenting picture is usually one of chronic symptoms rather than the acute, dramatic onset of a panic attack. Somatic symptom disorder and panic disorder can be (and often are) diagnosed together.
Consider ECG and pulse oximetry to rule out certain serious causes of panic; consider Holter monitoring. No specific lab tests are indicated except to rule out conditions in the differential diagnosis.
  • Finger-stick blood sugar in acute setting in a diabetic patient
  • Thyroid-stimulating hormone (TSH), electrolytes, CBC
  • Consider ordering echocardiogram if you suspect mitral valve prolapse.

Diagnostic Procedures/Other
If a medical cause of anxiety is strongly suspected, do the workup appropriate for that condition.
Combined antidepressant therapy and psychotherapy is superior to either alone during initial treatment for panic disorder (3)[A]. Cognitive-behavioral therapy (CBT) provides long-lasting treatment, often without subsequent need for medications.
CBT, tailored for panic disorder, consists of several steps: education, changing cognitions about the attack and the illness, relaxation and controlled breathing techniques, and, if appropriate, exposure to anxiety-provoking conditions coupled with in vivo relaxation exercises.
  • Medication management is indicated if psychotherapy is not successful (or not available) and may be combined with psychotherapy.
  • Patient preference plays a big part in this decision.
  • Because patients typically are anxious about their treatment, the therapeutic alliance is critical for the chronic care of this disorder.
  • If medications are started, they should be maintained for at least 6 months after symptom control.
First Line
  • FDA-approved choices for the treatment of panic disorder include sertraline, paroxetine, fluoxetine, alprazolam, and clonazepam, but avoid giving benzodiazepines to those with a history of substance abuse or who are currently abusing alcohol or benzodiazepines, unless following a detoxification protocol.
  • Most antidepressants except bupropion may treat panic disorder, but fluoxetine and selegiline patch can cause more initial nervousness than other antidepressants.
  • In nonbipolar patients, start a low-dose SSRI (e.g., 5 mg (escitalopram, 25 mg sertraline, 10 mg paroxetine) and consider doubling the dose after 2 or 3 weeks; while waiting for the antidepressant to work, schedule frequent visits, give the patient reassurance, teach a relaxation technique, encourage the patient to do vigorous aerobic exercise as soon as a panic attack begins (if medically appropriate and in an appropriate situation); refer the patient to a competent therapist for CBT (4)[A].
  • In bipolar patients, panic symptoms often resolve when treated with a mood stabilizer rather than an antidepressant (which may cause mania).
Second Line
  • Among serotonin-norepinephrine reuptake inhibitors, Venlafaxine extended release (ER) is effective. Start at 37.5 mg/day and titrate up to 75 mg/day after 7 days (maximum dose of 225 mg/day). Taper slowly over weeks to discontinue. Risk of hypertension at higher doses (5)[A].
  • Tricyclic antidepressants, particularly imipramine (start 25 mg/day in the evening and increase up to 25 mg every 3 days to a maximum of 200 mg/day); slower titration and lower doses are often as effective. Imipramine is as efficacious as SSRIs in the treatment of panic disorder. Tricyclic antidepressants are considered second line because of difficulty in dosing, more side effects, and greater risk associated with overdose compared with SSRIs (6)[A].
  • Benzodiazepines like alprazolam (start 0.5 mg TID and up to 5 mg/day) and (clonazepam (0.25 mg BID to target 1 mg/day) are FDA approved for panic disorder. Clonazepam has a longer half life, less interdose anxiety and lower abuse potential than alprazolam.
Consider referral to a psychiatrist for panic disorder that is comorbid with bipolar disorder, borderline personality disorder, schizophrenia, suicidality, alcohol, or substance abuse.
Aerobic exercise reduces symptoms better than placebo (7)[B].
Admission Criteria/Initial Stabilization
  • If certain life-threatening mimics of panic disorder have not been ruled out, such as a myocardial infarction (MI) or pulmonary embolus (PE), hospitalize patient to complete the evaluation.
  • If a panic disorder patient has concrete suicidal ideation, a psychiatric admission is indicated.
  • www.nlm.nih.gov/medlineplus/panicdisorder.html
  • Patient information handouts in American Family Physician. 2005;71:740 and 2006;74:1393.
  • http://www.nimh.nih.gov/health/publications/panic-disorder-when-fear-overwhelms/index.shtml
  • Most patients recover with treatment.
  • It can recur, but treatment of recurrence is usually successful.
1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617-627.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
3. Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev. 2007;(1);CD004364.
4. Otto MW, Tuby KS, Gould RA, et al. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry. 2001;158(12):1989-1992.
5. Pollack MH, Lepola U, Koponen H, et al. A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Depress Anxiety. 2007;24(1):1-14.
6. Bakker A, van Balkom AJ, Spinhoven P. SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatr Scand. 2002;106(3):163-167.
7. Broocks A, Bandelow B, Pekrun G, et al. Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic disorder. Am J Psychiatry. 1998;155(5):603-609.
See Also
Algorithm: Anxiety
  • F41.0 Panic disorder without agoraphobia
  • F40.01 Agoraphobia with panic disorder
  • F43.0 Acute stress reaction
Clinical Pearls
Encouraging patients (who are medically able) to do 10 minutes of vigorous aerobic exercise the moment a panic attack seems to be starting is often a very effective way to help patients feel safe during panic attacks. Always evaluate a patient with panic for suicidality. Patients with panic disorder are at increased risk for suicide, particularly if depressed.