Anxiety disorders

Anxiety disorders cover a broad spectrum of conditions characterized by excessive and persistent fear (an emotional response to imminent threats), anxiety (the anticipation of a future threat), worry (apprehensive expectation), and/or avoidance behavior. The etiology of anxiety disorders is multifactorial and may involve genetic, developmental, environmental, neurobiological, cognitive, and psychosocial factors. Therapy typically consists of a combination of pharmacotherapy, especially selective serotonin reuptake inhibitors (SSRIs), and psychotherapy, especially cognitive behavioral therapy (CBT).

• Description
  • Excessive and persistent fear; (an emotional response to imminent threats), anxiety; (the anticipation of a future threat), worry; (apprehensive expectation), and/or avoidance behavior
  • Physical manifestations that are disproportionate to the real magnitude of the trigger
  • Not due to substance abuse, medical disorder (e.g. pheochromocytoma, hyperthyroidism), or other psychiatric conditions
  • Anxiety disorders include panic disorder, phobias, generalized anxiety disorder, and selective mutism (for selective mutism see “emotional and behavioral disorders in children and adolescents”).

• Neurobiological factors
  • Disruption of the serotonin system
  • Dysfunction of GABAergic inhibitory transmission
• Substance use (leading to substance/medication-induced anxiety disorder)
• Environmental and developmental factors
  • Stress
  • Smoking (risk factor for panic disorder and panic attacks)
  • Psychological trauma, esp. during childhood
• Other medical conditions: conditions that may lead to anxiety and/or panic attacks
  • Endocrine disease (e.g., hyperthyroidism)
  • Cardiovascular disorders (e.g., congestive heart failure)
  • Respiratory illness (e.g., asthma)
  • Metabolic disorders (e.g., porphyria)
  • Neurological diseases (e.g., encephalitis)

• Definition: an anxiety disorder in which patients have anxiety that is prolonged, excessive, persistent (> 6 months), and caused by various aspects of daily life instead of a single specific situation or object
• Epidemiology ^[1]
  • Most common anxiety disorder among the elderly population
  • Lifetime prevalence: 5–10%
  • ♀ > ♂ (2:1)
• Clinical features: diagnosis is confirmed if the following symptoms occur more days than not for at least 6 months (≥ 1 symptom in children, ≥ 3 in adults)
  • Nervousness, restlessness
  • Irritability
  • Muscle tension
  • Somnolence, fatigue
  • Concentration difficulties
  • Insomnia
• Differential diagnosis
  • Panic disorder
    • Panic attacks may also occur in generalized anxiety disorder (GAD).
    • Panic symptoms in GAD are generally precipitated by the uncontrolled escalation of anxiety/worry rather than occurring spontaneously or acutely in specific situations as in panic disorder.
  • Depressive disorders
    • Individuals with GAD tend to be more concerned with the future.
    • Individuals with depressive disorders are more past-oriented.
    • Mood swings and suicidal ideation are uncommon in GAD.
  • Social anxiety disorder: Patients with GAD are usually comfortable in social situations and not particularly disturbed by the evaluation by others.
• Treatment ^[2]
  • First-line: psychotherapy, pharmacotherapy, or both
    • Psychotherapy: CBT , applied relaxation therapy, biofeedback
    • Pharmacotherapy: SSRIs/SNRI for at least 12 months ^[3]
  • Second-line
    • TCAs
    • Benzodiazepines can be used until SSRIs take effect but should never be used for long-term management, as they increase the risk of benzodiazepine dependence.
    • Buspirone
  • Antipsychotics only for refractory cases
• Special patient groups: perinatal generalized anxiety disorder
  • Definition: generalized anxiety that occurs from pregnancy through one year postpartum
  • Epidemiology: Prevalence during pregnancy is ∼ 10%. ^[4]
  • Risk factors
    • History of anxiety or mood disorders
    • Family history of anxiety disorders
  • Clinical features
    • Disproportionate, overwhelming fears about fetal and/or paternal well-being (e.g., excessive concerns about baby's health)
    • Functional impairment, such as inability to work (in moderate to severe anxiety)
    • Physical symptoms (e.g., fatigue, insomnia, muscle tension)
  • Treatment
    • Psychotherapy for mild symptoms
    • Psychotherapy and/or pharmacotherapy (e.g., SSRIs, SNRIs) for moderate to severe anxiety
    • Treatment is required if symptoms cause functional impairment.

Don't get anxious if the BUS doesn’t arrive at ONE; just take a BUSpirONE.

References:^[5]

Definition

An abrupt episode of intense fear associated with physical and cognitive symptoms ^[6][7]

Etiology ^[6][8]

• Panic disorder
• Anxiety due to another medical condition
• Substance/medication-induced anxiety disorder
• Other anxiety disorders (e.g., specific phobias)
• Other psychiatric disorders (e.g., psychotic disorders)

Clinical features ^[8]

Acute panic attacks peak within several minutes and involve ≥ 4 of the following cognitive and/or somatic symptoms:

• Cognitive symptoms
  • Fear of dying
  • Fear of losing control
  • Derealization or depersonalization
• Somatic symptoms: overstimulation of the sympathetic system
  • Palpitations, tachycardia, or pounding heart
  • Sweating or diaphoresis
  • Trembling or shaking
  • Shortness of breath or smothering sensation
  • Choking sensation
  • Chest pain or tightness
  • Abdominal discomfort or nausea
  • Dizziness, light-headedness, or faintness
  • Chills or feeling hot
  • Paresthesias

“STUDENTS FEAR the 3Cs:” Sweating, Trembling, Unsteadiness (dizziness), Derealization, Elevated heart rate (palpitations), Nausea, Tingling, and Shortness of breath; FEAR of dying or going crazy; Chest pain, Choking, and Chills.

Diagnosis

• Clinical diagnosis based on typical clinical features and the exclusion of organic causes of symptoms ^[6][7]
• Consider basic investigations, e.g. : ^[6]
  • CBC
  • BMP
  • Thyroid function tests
  • Serum and urine toxicology screen
  • ECG
• Consider further targeted investigation if an underlying medical cause is suspected (see “Differential diagnosis”).

Differential diagnosis

Consider the following based on the presenting clinical feature:

• Differential diagnosis of chest pain
• Differential diagnosis of dyspnea
• Differential diagnosis of syncope and presyncope
• Differential diagnoses of stroke
• Differential diagnosis of abdominal pain
• Differential diagnosis of cardiac arrhythmias
• Differential diagnosis of sepsis

Management of acute panic attack ^[9][10]

• Rule out life-threatening causes of symptoms, e.g.:
  • Red flags in dyspnea
  • Red flags in chest pain
  • Thyroid storm
• Immediate interventions may include:
  • Reassurance
  • Deep breathing and relaxation techniques
  • Short-acting benzodiazepine (e.g., alprazolam ) if nonpharmacological intervention fails
  • See also “Acute management” in “Hyperventilation syndrome” and “Approach to the agitated or violent patient.”
• Once life-threatening causes are excluded, consider discharge to primary care or psychiatry for close follow-up. ^[6]
• Evaluate for underlying psychiatric disorder and assess suicidal risk.
• See “Management” in “Panic disorder” for long-term treatment of recurrent panic attacks.

Panic attacks typically self-resolve within 30 minutes of onset and may not require acute intervention. ^[9]

• Definition: : recurrent spontaneous and unexpected panic attacks that often occur without a known trigger
• Epidemiology ^[11]
  • Lifetime prevalence: approx. 5% of the population ^[12]
  • Most common in patients aged 26–34 years
  • ♀ > ♂ (2:1)
• Etiology
  • Strong genetic disposition
  • Associated conditions
    • Agoraphobia
    • Substance use
    • Depression
    • Bipolar disorder
• Diagnosis ^[5]
  • Recurrent panic attacks, at least one of which is followed by ≥ 1 of the following:
    • Persistent concern about having another panic attack
    • Persistent concern about the consequences of another panic attack (e.g., losing control)
    • Significant maladaptive behavioral changes in response to the attacks (e.g., avoiding a situation in which a previous attack occurred)
  • The panic attacks are not attributable to:
    • Effects of a medication or substance
    • Another mental disorder (e.g., specific phobias, social anxiety disorder)
• Management
  • Immediate: See “Management of acute panic attack.”
  • Long-term
    • CBT
    • Antidepressants: SSRIs, SNRIs (venlafaxine), TCAs
    • Benzodiazepines may be used until antidepressants take effect.
• Complication: Risk of suicide is increased

• Definition: pronounced anxiety lasting ≥ 6 months of social situations that might involve scrutiny by others
• Epidemiology
  • One of the most common mental disorders
  • Lifetime prevalence: approx. 5–10% of the population ^[13]
  • Peak incidence: adolescence and early adulthood
  • ♀ > ♂ (2:1)
• Types
  • Social anxiety disorder (SAD): fear/anxiety out of proportion to a social situation where one may be scrutinized by others (e.g., meeting new people at a party, eating in public)
  • Performance-only SAD: symptoms of fear/anxiety restricted only to public speaking or performing in front of crowds
  • Paruresis (shy bladder syndrome): fear/anxiety associated with urinating when other people are present, e.g., in public restrooms
• Clinical features
  • Blushing, palpitations, sweating during a social interaction
  • Anticipatory anxiety (e.g., worrying weeks in advance about attending a social event)
  • Anxiety driven by fear of embarrassment and others noticing the reaction
  • Avoidance of the aforementioned triggers (e.g., not attending parties, refusing to attend school)
  • In children: refusing to speak at social events, crying/throwing a tantrum, clinging to their caregiver
• Treatment
  • CBT for SAD and performance-only SAD
  • Pharmacotherapy for SAD
    • First-line pharmacotherapy: SSRIs/SNRIs (e.g., venlafaxine)
      • No/partial response to SSRIs/SNRIs and no history of a substance use disorder: clonazepam
      • No/partial response to SSRIs/SNRIs and a history of a substance use disorder: phenelzine
  • Pharmacotherapy for performance-only SAD: beta blockers (e.g., propranolol) OR benzodiazepines (e.g., clonazepam)
    • Given on an as-needed basis
    • Taken 30–60 minutes before an anxiety-causing event

References:^[5][14]

• Definition
  • Persistent (≥ 6 months) and intense fears of one or more specific situations or objects (phobic stimuli)
  • Always occurs during encounters with the phobic stimulus but may already surge in anticipation of an encounter
• Epidemiology
  • Lifetime prevalence: up to 10% of the population ^[15]
  • The average age of onset depends on the specific phobia (e.g., animal phobias more commonly develop in early childhood).
  • ♀ > ♂ (2:1)
• Common phobias
  • Animal: spiders (arachnophobia), insects (entomophobia), dogs (cynophobia)
  • Natural environment: heights (acrophobia), storms (astraphobia)
  • Blood-injection-injury: blood (hematophobia), needles (belonephobia), dental procedures (odontophobia), fear of injury (traumatophobia)
  • Situational: enclosed places (claustrophobia), flying (aviophobia)
  • Other: fear of vomiting (emetophobia), the number 13 (triskaidekaphobia), costumed characters (masklophobia), fear of clowns (coulrophobia)
• Treatment
  • First-line: CBT with exposure therapy
  • Second-line: pharmacotherapy (may be attempted if patients prefer medication to CBT or if CBT is not available)
    • Preferred: benzodiazepines
    • Alternative: SSRIs (limited evidence)
  • Acute management of needle phobia (blenophobia) ^[16][17][18]
    • Reassurance
    • Topical anesthesia: e.g., eutectic mixture of local anesthetic (EMLA) cream
    • Applied tension: repeated flexing of skeletal muscles to prevent vasovagal response

• Definition: pronounced fear or anxiety of being in situations that are perceived as difficult to escape from or situations in which it might be difficult to seek help
• Epidemiology
  • ♀ > ♂ (2:1)
  • Age of onset: < 35 years (60–70% of cases)
• Clinical features
  • Fear, anxiety, or even panic attacks over a period of ≥ 6 months in ≥ 2 of the following 5 situations:
    • Using public transportation
    • Being in open spaces
    • Being in enclosed places
    • Standing in line or being in a crowd
    • Being outside of the home alone
  • Active avoidance of these settings unless a companion is present
  • Fear can become so severe that the affected individual feels unable to leave the house.
  • Some patients can have comorbid panic disorder.
• Treatment
  • Cognitive behavioral therapy
  • Selective serotonin reuptake inhibitors

If a patient meets the criteria for panic disorder and agoraphobia, both conditions should be diagnosed.

References:^[8]

Background ^[19][20][21]

• Definition: : a condition characterized by an increase in minute ventilation that exceeds metabolic demands without a clear organic precipitant
• Etiology: : frequently associated with panic disorder and anxiety disorder
• Pathophysiology: hyperventilation → hypocarbia → respiratory alkalosis ^[22]

Clinical features ^[23]

• Cardinal feature: transient hyperventilation
  • Additional symptoms include:
    • Dizziness, lightheadedness
    • Chest pain, palpitations
    • Paresthesias (typically in extremities and/or the perioral area)
    • Carpopedal spasm
    • Anxiety, sense of impending doom

Diagnosis ^[23][24]

Hyperventilation syndrome is a diagnosis of exclusion.

• Pulse oximetry: SpO₂ is usually normal.
• Capnography (if available): low EtCO₂ initially (normalizes as the episode resolves)
• Tests to rule out an organic cause may include:
  • Bedside tests
    • POC glucose
    • ECG
    • Peak expiratory flow
  • Laboratory tests
    • CBC
    • BMP (including calculation of anion gap)
    • VBG or ABG
  • Imaging (as indicated by clinical suspicion), e.g.:
    • CXR
    • CT angiogram chest
    • CT head

Differential diagnosis

See also “Differential diagnosis of dyspnea.”

• Metabolic acidosis (Kussmaul breathing)
  • Diabetic, alcoholic, and/or starvation ketoacidosis
  • Lactic acidosis due to salicylate poisoning
  • Methanol poisoning or ethylene glycol poisoning
  • AKI or advanced CKD
• Cardiac
  • Acute coronary syndrome, myocardial infarction
  • Congestive heart failure
• Pulmonary
  • Pulmonary embolism
  • Acute asthma exacerbation or COPD exacerbation
  • Emphysema (due to COPD, α1-antitrypsin deficiency)
  • Pneumothorax
  • Acute respiratory distress syndrome (ARDS)
• Endocrine
  • Hyperthyroidism
  • Pheochromocytoma
  • Hypoglycemia
  • Hypocalcemia
• CNS disorders
  • Elevated ICP
  • Brainstem tumors
  • Grand mal seizure
• Other
  • Infection (e.g., malaria), sepsis
  • Pregnancy
  • Cheyne-Stokes breathing

Acute management ^[23]

• Exclude immediately life-threatening causes of dyspnea.
• First-line: nonpharmacological treatment
  • Offer patient reassurance and if possible, remove stressors.
  • Breathing retraining: Focus on diaphragmatic breathing.
• Second-line: short-acting benzodiazepines (e.g., alprazolam ) if nonpharmacological interventions fail.
• Interventions to reduce pH directly are typically not necessary.
• See also “Management of acute panic attack” and “Approach to the agitated or violent patient.”

Rebreathing into a paper bag can cause significant hypoxemia and is therefore not recommended. ^[25]

Abnormal findings on physical exam (e.g., jugular venous distention, wheezing, crackles, altered mental status) suggest a diagnosis other than hyperventilation syndrome.

• Definition: prominent anxiety or panic attacks within 1 month of use of, or withdrawal from, a substance/medication that is capable of inducing anxiety symptoms ^[26]
• Etiology ^[27][28]
  • Alcohol
  • Caffeine
  • Anticonvulsants, opioids, and sedatives
  • Anticholinergics
  • Bronchodilators
  • Corticosteroids
  • Amphetamines, cocaine, cannabis, phencyclidine, hallucinogens, and inhalants
• Clinical features ^[8][26][29]
  • Fear, anxiety, or panic attacks over a period of 1 month after taking or stopping the substance/medication
  • Physical symptoms such as palpitation, dizziness, shaking, shortness of breath, and sweating
  • Generalized anxiety or phobia may accompany the substance-induced anxiety
• Treatment
  • Discontinuation of the substance/medication
  • CBT
  • Antidepressants (e.g., SSRIs, SNRIs, TCAs, buspirone)

Patients should be evaluated for medical conditions that can cause anxiety. Anxiety due to another medical condition is diagnosed if the condition was diagnosed before the onset of anxiety. Possible underlying conditions include:

• Endocrine disorders: e.g., hyperthyroidism, pheochromocytoma, hypoglycemia, hyperadrenalism, hypercortisolism
• Cardiovascular disorders: e.g., congestive heart failure, pulmonary embolism, arrhythmia (e.g., atrial fibrillation)
• Respiratory disorders: e.g., asthma, COPD, pneumonia
• Infectious diseases: e.g., epiglottitis
• Metabolic disorders: e.g., porphyria, vitamin B₁₂ deficiency
• Neurological disorders: e.g., neoplasm, vestibular dysfunction, encephalitis, seizure disorders
• Gynecological disorders: e.g., genito-pelvic penetration disorder, hydatidiform mole
• Other: e.g., menopause, insomnia, fibromyalgia, schizophrenia, gender dysphoria

• Description: : a disorder characterized by excessive fear, anxiety, or avoidance of separation from major attachment figures
  • Separation anxiety disorder differs from nonpathological separation anxiety in its intensity and effect on the social and academic life of the individual.
  • Separation anxiety is normal in children under a developmental age of 3 years. ^[30]
  • Typically develops after a stressful life event, usually involving some form of loss (e.g., death of a relative, parental divorce, change of school)
  • Onset: the condition can occur in, or persist into, adulthood and may have a debilitating effect on an individual's ability to work or socialize in the absence of attachment figures.
• Diagnostic criteria (DSM-V) ^[5]
  • Fear of separation from major attachment figures, that is excessive for developmental level, involving at least 3 of the following features:
    • Recurrent and excessive distress prior to, or during, separation
    • Persistent worrying about the loss of attachment figures (e.g., due to illness, injury, or death)
    • Persistent worrying about separation due to the individual being lost, kidnapped, injured, or ill
    • Persistent reluctant to leave home due to fear of separation
    • Avoidance of being left alone (e.g., at home or elsewhere)
    • Avoidance of falling asleep, or sleeping away from home, without major attachment figure
    • Persistent nightmares about separation
    • Persistent somatic symptoms (e.g., headaches, nausea/vomiting, abdominal pain)
  • Duration: symptoms persist for at least 4 weeks in children/adolescents and 6 months in adults
  • Significant impairment of academic, social, and/or work life (e.g., often a precursor to school refusal)
  • Symptoms are not attributable to another psychiatric disorder (e.g., autism spectrum disorder, psychosis, other anxiety disorders).

• Treatment ^[31]
  • Psychotherapy
    • All age groups: cognitive behavioral therapy (e.g., exposure therapy)
    • Children: family therapy and parent-child interaction therapy
  • Pharmacotherapy: SSRIs (e.g., fluoxetine) indicated as an adjunct to psychotherapy if there is moderate to severe functional impairment
• Complications
  • Children: academic and social consequences of school refusal
  • Adults: depression and panic disorder ^[30]

Children under 3 years of age commonly undergo periods of separation anxiety from attachment figures as a normal part of their development. The diagnosis of separation anxiety disorder should only be considered if the symptoms become excessive for developmental level. ^[30]

• Description: a psychiatric disorder characterized by the inability to speak in specific social situations (e.g., during class)
  • Typically normal development of language and speech.
  • Onset: generally before 5 years of age, although may not become clinically relevant until the child is required to perform verbally (e.g., with the start of school)
• Diagnostic criteria (DSM-V) ^[5]
  • Consistent inability to speak in specific social settings where speaking is expected (e.g., does not speak in class but speaks at home)
  • Interferes with academic or professional performance and social interaction
  • Duration of symptoms: at least 1 month
  • The inability to speak is not due to difficulties or discomfort with the spoken language expected in the social situation.
  • The inability to speak is not attributable to schizophrenia spectrum disorder or another psychotic disorder, autism spectrum disorder, or a communication disorder.
• Treatment ^[32]
  • Psychotherapy
    • Cognitive behavioral therapy (e.g., exposure therapy) at all ages
    • Children: family therapy and parent-child interaction therapy
  • Pharmacotherapy: SSRIs (e.g., fluoxetine) may be beneficial in those who do not respond to psychotherapy
• Complications: may coexist with social anxiety disorder and may also result in school refusal

• One-Minute Telegram 78-2023-1/3: USPSTF recommends screening adults for major depressive disorder and anxiety disorders

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