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).

For separation anxiety disorder and selective mutism, see the article on “Emotional and behavioral disorders in children and adolescents.”

• 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: prolonged and excessive anxiety that:
  • Is not focused on a single specific fear but may revolve around certain themes (e.g., health, work)
  • Causes clinically significant distress
  • Is not caused by substance use, medication, or underlying medical condition
• 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
      • Mechanism of action: 5-HT_1A receptor stimulation
      • Requires consistent daily intake for at least two weeks because of its delayed onset of action
      • Advantages
        • Is not sedative
        • No risk of addiction or tolerance
        • No interaction with alcohol (as opposed to barbiturates and benzodiazepines)
    • Antipsychotics only for refractory cases

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

References:^[4]

• Definition: : recurrent spontaneous and unexpected panic attacks that often occur without a known trigger
• Epidemiology ^[5]
  • Lifetime prevalence: approx. 5% of the population ^[6]
  • Most common in patients aged 26–34 years
  • ♀ > ♂ (2:1)
• Etiology
  • Strong genetic disposition
  • Associated conditions
    • Agoraphobia
    • Substance use
    • Depression
    • Bipolar disorder
• Clinical features
  • Recurrent panic attacks: episodes of intense fear and discomfort that peak within several minutes
    • Fear of dying and/or losing control
    • Overstimulation of the sympathetic system
      • Sweating, palpitations, shaking
      • Paresthesias
      • Abdominal pain, nausea
      • Light-headedness, chest pain
      • Shortness of breath, choking sensation
      • Depersonalization, derealization
• Diagnostics: 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)
• Treatment
  • Acute panic attack
    • Reassurance and breathing exercise
    • Short-acting benzodiazepine (e.g. alprazolam)
  • Long-term management
    • CBT
    • Antidepressants: SSRIs, SNRIs (venlafaxine), TCAs
    • Benzodiazepines may be used until antidepressants take effect.
• Complication: Risk of suicide is increased.

“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.

• 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 ^[7]
  • 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:^[4][8]

• 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 ^[9]
  • 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 (blenophobia), 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: Cognitive-behavioral therapy with exposure therapy
  • Alternative: SSRIs OR benzodiazepine

• 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:^[10]

• 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 ^[11]
• Clinical features
  • 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
• Diagnostics: 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 include:
    • ECG: to rule out myocardial infarction
    • Serum glucose: to rule out hyperglycemia in diabetic ketoacidosis
    • CBC: to rule out leukocytosis in case of sepsis/infection
    • BUN, creatinine, and electrolytes (including calculation of anion gap): to rule out chronic kidney disease
    • Arterial blood gas: to rule out underlying cardiopulmonary disease (e.g., pulmonary embolism) and metabolic derangement (e.g., lactic acidosis)
    • Peak expiratory flow: to rule out asthma and chronic obstructive pulmonary disease (COPD)
    • Imaging: to rule out pneumothorax, pulmonary embolism, pneumonia, and congestive heart failure
• Differential diagnoses
  • Acute coronary syndrome, myocardial infarction
  • Congestive heart failure
  • Metabolic acidosis
    • Diabetic, alcoholic, and/or starvation ketoacidosis
    • Lactic acidosis due to salicylate poisoning
    • Methanol poisoning or ethylene glycol poisoning
  • Chronic kidney failure
  • Pulmonary embolism
  • Acute exacerbations of asthma or COPD
  • Emphysema (due to COPD, α1-antitrypsin deficiency)
  • Pneumothorax
  • Hyperthyroidism, pheochromocytoma, hypoglycemia, and/or hypocalcemia
  • Pregnancy
  • Infection (e.g., malaria), sepsis
  • CNS disorders (e.g., grand mal seizure, brainstem tumors)
  • Acute respiratory distress syndrome (ARDS)
• Management
  • Patient reassurance
  • If possible, removal of any stressors
  • Breathing retraining: The patient should focus on abdominal (diaphragmatic) breathing.
  • Interventions to reduce pH directly are typically not necessary.
  • Rebreathing into a paper bag can cause significant hypoxemia and, therefore, is not recommended. ^[12]

References:^[13][14][15]

• 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 ^[16]
• Etiology ^[17][18]
  • Alcohol
  • Caffeine
  • Anticonvulsants, opioids, and sedatives
  • Anticholinergics
  • Bronchodilators
  • Corticosteroids
  • Amphetamines, cocaine, cannabis, phencyclidine, hallucinogens, and inhalants
• Clinical features ^[10][16][19]
  • 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