Anxiety disorders

Anxiety disorders cover a broad spectrum of conditions characterized by excessive and persistent fear (an emotional response to real or perceived 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, 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 real or perceived 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
• Anxiety disorders include generalized anxiety disorder, panic disorder, specific phobias, and selective mutism.

Comparison of anxiety disorders

• Neurobiological and genetic factors
  • Disruption of the serotonin system
  • Dysfunction of GABA inhibitory transmission
• Environmental, developmental, and psychosocial factors
  • Stress
  • Smoking (risk factor for panic disorder and panic attacks)
  • Psychological trauma, especially during childhood
• Substance use in substance/medication-induced anxiety disorder
• Anxiety due to another medical condition (e.g., hyperthyroidism, asthma)

Definition

• An anxiety disorder characterized by excessive and persistent anxiety for ≥ 6 months
• Symptoms can be triggered in various situations, with or without an identifiable stressor, and cause significant social or occupational dysfunction.

Epidemiology ^[1]

• Lifetime prevalence: 4–7% ^[2]
• Typically adult onset ^[1]
• ♀ > ♂ (2:1) ^[3]

Clinical features ^[2]

• Prolonged, excessive, pervasive worrying and anxiety
• Nervousness, restlessness
• Irritability
• Muscle tension
• Somnolence, fatigue
• Concentration difficulties
• Insomnia
• Medically unexplained physical symptoms (e.g., chest pain, racing heart)

Screening ^[4][5]

• Indicated for all individuals aged 8–64 years. ^[4][5]
• Screening tools include:
  • Adults: GAD-2 , GAD-7
  • Postpartum individuals: Edinburgh Postnatal Depression Scale (EPDS) anxiety subscale ^[6]
  • Children and adolescents: Patient Health Questionnaire for Adolescents, Screen for Child Anxiety Related Disorders ^[4][7][8]

Diagnostics ^[2][9]

Approach

• Consider GAD in those with a positive screening or who express pervasive worrying, anxiety, and/or medically unexplained physical symptoms.
• Perform a complete patient history and physical examination.
• Consider diagnostic studies to rule out organic causes.
• Confirm the diagnosis using the DSM-5 criteria for GAD.
• Assess for psychiatric and medical comorbidities, including substance use disorder.
• Evaluate suicide risk.
• Consult psychiatry if there is diagnostic uncertainty or concern for comorbid psychiatric conditions.

Up to 80% of individuals with GAD have a psychiatric comorbidity, e.g., major depressive disorder or social anxiety disorder. ^[1][2]

Exclusion of organic causes ^[2]

Consider the following studies based on clinical suspicion.

• Thyroid function tests to rule out thyroid disease
• CBC to rule out anemia
• ECG to rule out acute coronary syndromes
• Urine drug screen to rule out substance use or poisoning
• Plasma free metanephrines in patients with a family history or clinical features of pheochromocytoma

DSM-5 diagnostic criteria for GAD ^[3]

Diagnosis is confirmed in individuals who meet all of the following criteria.

• Excessive anxiety and worry about multiple events and/or activities (e.g., school, work) on most days for ≥ 6 months
• Worry that is difficult to control
• ≥ 3 (in adults) or ≥ 1 (in children) of the following symptoms occurring on most days over the past 6 months:
  • Sleep disturbances
  • Muscle tension
  • Irritability
  • Difficulty concentrating
  • Fatiguing easily
  • Restlessness
• Symptoms that cause significant distress or impairment in the professional, social, or other important areas
• Symptoms not attributable to substance use, a medical disorder (e.g., pheochromocytoma, hyperthyroidism), or other psychiatric conditions (e.g., panic disorder, PTSD, somatic symptom and related disorders)

Differential diagnoses ^[2]

• Other anxiety disorders
  • Anxiety due to another medical condition
  • Panic disorder
    • Panic attacks in GAD are generally precipitated by the uncontrolled escalation of anxiety and/or worry.
    • Panic attacks in panic disorder are sudden and unexpected.
  • Social anxiety disorder: Patients with GAD are usually comfortable in social situations and are not particularly anxious about public scrutiny.
  • Substance/medication-induced anxiety disorder
• Acute stress disorder, PTSD
• OCD
• Mood disorders, e.g., major depressive disorder (MDD), bipolar disorder
  • Individuals with GAD tend to worry about the future, whereas those with MDD are typically anxious about the past.
  • Mood swings and suicidal ideation are uncommon in GAD.
• Substance withdrawal, e.g., alcohol, benzodiazepines, opioids

Management ^[2][9]

General principles

• Therapeutic options for GAD are psychotherapy and/or pharmacotherapy.
• Lifestyle modifications can help reduce and/or prevent symptoms.
• Treatment response is measured using validated tools, e.g., GAD-7.
• Consider indications for specialist referral, e.g., no improvement after first-line treatment.
• Consider hospitalization for patients with intractable symptoms and/or suicidal ideation.

A combination of psychotherapy and pharmacotherapy is more effective than either treatment approach alone. ^[9]

Psychotherapy

• CBT (preferred)
  • May include exposure therapy, psychoeducation, goal setting, relaxation, and/or cognitive restructuring
  • Typically 12 sessions with homework ^[2]
• Other options include supportive psychotherapy, applied relaxation therapy, psychodynamic therapy, acceptance and commitment therapy, and biofeedback.

Pharmacotherapy ^[2]

• First-line agents
  • SSRIs, e.g., escitalopram , paroxetine , sertraline (off-label) ^[2]
  • SNRIs, e.g., duloxetine , venlafaxine
• If no improvement after 8 weeks at the therapeutic dose: Switch to a different first-line agent.
• Alternative agents may be considered if there is no improvement with first-line therapy.
  • Buspirone
  • Benzodiazepines (e.g., alprazolam, diazepam) for short-term use only
  • Pregabalin
  • Atypical antipsychotics (e.g., risperidone, quetiapine)
  • Hydroxyzine
  • TCAs, e.g., imipramine

Cannabis can trigger psychiatric disorders, and there is no scientific evidence to recommend its use in patients with anxiety disorders. ^[9]

Long-term use of benzodiazepines is associated with significant adverse effects (e.g., motor and cognitive impairment) and risk of dependence. ^[2]

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

Lifestyle modifications

• Sleep hygiene
• Exercise
• Avoidance of caffeine, alcohol, and recreational drugs
• Smoking cessation
• Mindfulness (meditation, mindfulness-based stress reduction)

Indications for referral

Refer to a psychiatrist in any of the following situations.

• The patient has comorbid psychiatric and/or substance use disorders.
• There is no improvement with first-line treatment, i.e., a full course of CBT and/or 1–2 trials of SSRI or SNRI.
• Long-term benzodiazepines, TCAs, or antipsychotics are being considered.
• The patient does not tolerate pharmacotherapy.

Special patient groups

Perinatal generalized anxiety disorder ^[10]

• Definition: GAD that occurs during pregnancy and/or up to one year postpartum
• Epidemiology: ∼ 10% prevalence ^[10]
• Risk factors
  • History of anxiety or mood disorders
  • Family history of anxiety disorders
• Clinical features
  • Time-consuming, overwhelming, intrusive fears about illness, mortality, and well-being of the fetus, oneself, and the other parent
  • Functional impairment, such as inability to perform regular activities (in moderate to severe anxiety)
  • Physical symptoms (e.g., fatigue, insomnia, muscle tension)
  • Comorbid MDD (common)
• Screening: Screen all pregnant and postpartum individuals using, e.g., GAD-7 , EPDS anxiety subscale ^[5][6][11]
• Diagnostics: Confirm diagnosis using the DSM-5 criteria for GAD.
• Treatment
  • Mild symptoms: CBT (preferred) or another type of psychotherapy
  • Mild to moderate symptoms: SSRI or SNRI
  • Moderate to severe symptoms: CBT and SSRI or SNRI, consider referral to psychiatry

Definition

An acute panic attack is an abrupt episode of intense fear associated with physical and cognitive symptoms. ^[12][13]

Etiology ^[3][12]

• 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 ^[3]

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.

Diagnostics

• Clinical diagnosis based on typical clinical features and the exclusion of organic causes of symptoms ^[12][13]
• Consider basic investigations, e.g. : ^[12]
  • 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 diagnoses

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 ^[14][15]

• 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. ^[12]
• 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. ^[14]

Definition

Panic disorder is an anxiety disorder characterized by recurrent, unexpected panic attacks in addition to a ≥ 1-month period of persistent worry about experiencing additional attacks or their consequences, and/or maladaptive behavior to avoid further episodes.

Epidemiology ^[16]

• Lifetime prevalence: 1–4% of the population ^[17]
• Peak incidence: adults aged 26–34 years ^[16]
• ♀ > ♂ (2:1)

Etiology ^[9]

• Strong genetic predisposition ^[9]
• Associated conditions
  • Agoraphobia
  • Substance use disorder
  • Comorbid mood disorders, e.g., major depressive disorder (MDD), bipolar disorder

Clinical features ^[9]

• Recurrent panic attacks characterized by:
  • Symptoms that peak within minutes
  • Somatic symptoms, e.g., palpitations, chest pain or tightness, tremor
  • Cognitive symptoms, e.g., fear of dying
• Persistent worry about future panic attacks
• Avoidance of triggering situations

Diagnostics ^[9]

Approach

• Consider panic disorder in patients with recurrent panic attacks.
• Perform a complete patient history and physical examination.
• Consider diagnostic studies to rule out organic causes based on clinical evaluation. ^[12]
• Confirm the diagnosis using DSM-5 criteria.
• Assess for psychiatric and medical comorbidities, e.g., MDD, substance use disorder.
• Evaluate suicide risk.

Exclusion of organic causes

Consider the following studies based on clinical suspicion.

• Thyroid function tests to rule out thyroid disease
• CBC to rule out anemia
• ECG to rule out acute coronary syndromes
• Urine drug screen to rule out substance use or poisoning
• BMP to rule out electrolyte disturbances

DSM-5 diagnostic criteria for panic disorder ^[3]

Diagnosis is confirmed in individuals who meet all of the following criteria.

• Recurrent panic attacks, during which ≥ 4 of the following symptoms occur:
  • Tachycardia, palpitations
  • Sweating
  • Shaking or trembling
  • Shortness of breath or sensation of smothering
  • Sensation of choking
  • Chest pain or discomfort
  • Abdominal distress or nausea
  • Dizziness, lightheadedness
  • Heat sensation or chills
  • Parasthesias
  • Depersonalization or derealization
  • Fear of losing control
  • Fear of dying
• ≥ 1 panic attacks followed by ≥ 1 month of one or both of the following:
  • Persistent concern about having another panic attack or about its consequences (e.g., losing control)
  • Significant maladaptive behavioral changes in response to the attacks (e.g., avoiding situations in which previous attacks occurred)
• Panic attacks are not attributable to:
  • Effects of a medication, substance, or medical condition
  • Another psychiatric disorder (e.g., specific phobias, social anxiety disorder)

Differential diagnoses ^[18]

• Other anxiety disorders
  • GAD
  • Substance/medication-induced anxiety disorder
  • Anxiety due to another medical condition
• Mood disorders, e.g., MDD, bipolar disorder
• Substance use disorder

Management ^[17][18]

See also “Management of acute panic attack.”

Patients with panic disorder are at increased risk of suicide. ^[9][18]

General principles

• Treatment options for panic disorder are psychotherapy and/or pharmacotherapy.
• Lifestyle modifications can help reduce symptoms.
• Treatment response is measured using the Panic Disorder Severity Scale.
• Consider indications for specialist referral, e.g., no improvement after first-line treatment.
• Consider hospitalization for patients with intractable symptoms and/or suicidal ideation.

Psychotherapy ^[17][18]

• CBT is the preferred modality.
• Consider especially for patients who decline or do not tolerate pharmacotherapy.
• Effectiveness is similar to pharmacotherapy.

Pharmacotherapy

• First-line
  • SSRIs, e.g., paroxetine , sertraline
  • SNRIs, e.g., venlafaxine
• Additional agents include:
  • Benzodiazepines, e.g., alprazolam, clonazepam, or diazepam, for short-term use only
  • TCAs

Cannabis can trigger psychiatric disorders, and there is no scientific evidence to recommend its use in patients with anxiety disorders.

Long-term use of benzodiazepines is associated with an increased risk of tolerance, dependence, and withdrawal. ^[18]

Indications for referral

Refer to a psychiatrist in any of the following situations.

• There is no improvement with first-line pharmacotherapy.
• The patient does not tolerate pharmacotherapy.
• The patient has comorbid psychiatric and/or substance use disorders.
• Long-term benzodiazepines or alternative agents (e.g., TCAs) are being considered.

Definition ^[3]

Social anxiety disorder is characterized by intense and disproportionate fear and/or anxiety of social situations in which the individual may be scrutinized or judged (e.g., meeting new people, parties, eating in public) that lasts for ≥ 6 months.

Epidemiology

• One of the most common psychiatric conditions
• 13% lifetime prevalence ^[19]
• Peak incidence: adolescence and early adulthood
• ♀ > ♂ (2:1)

Subtypes

• Performance-only social anxiety disorder: : an anxiety disorder characterized by intense fear and/or anxiety related to speaking or performing in public
• Paruresis (shy bladder syndrome): the inability to urinate in the presence of others ^[20]

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 fear and/or anxiety triggers (e.g., not attending parties, refusing to attend school)
• In children ^[3]
  • Refusing to speak at social events, crying, throwing a tantrum, clinging to caregiver
  • Symptoms occur both in peer settings and with adults.

Diagnostics ^[19]

Approach

• Consider screening individuals with other psychiatric or substance use disorders by asking about:
  • Avoidance of social situations or activities
  • Feeling anxious or embarrassed in social situations
• Confirm the diagnosis using the DSM-5 criteria.
• Assess for comorbidities, e.g., MDD, substance use disorders.

Individuals with social anxiety disorder often do not seek medical care for their psychological symptoms.

DSM-5 diagnostic criteria for social anxiety disorder ^[3]

Diagnosis is confirmed in individuals who meet all of the following criteria.

• Significant fear or anxiety related to social situations in which scrutiny by others is anticipated (e.g., conversing with or meeting unfamiliar people, eating or giving a speech in front of others)
• Fear of behaving in ways that will lead to negative judgment by others
• Fear or anxiety that is almost always triggered by social situations
• Avoidance of or intense anxiety during social situations
• Fear or anxiety that is disproportionate to the actual threat
• Symptoms that persist for ≥ 6 months
• Symptoms causing significant distress or functional impairment (e.g., social, occupational)
• Symptoms not attributable to or better explained by substance use or another psychiatric or medical condition

Differential diagnoses ^[19]

• Other anxiety disorders
  • Agoraphobia
  • Panic disorder
  • Generalized anxiety disorder
  • Separation anxiety disorder
• Shyness as a personality trait
• Medical conditions that cause embarrassing symptoms (e.g., incontinence, tremor)
• Avoidant personality disorder

Management ^[19][21]

Psychotherapy and pharmacotherapy can be offered together or alone based on patient preferences and clinical judgment.

• Psychotherapy: : CBT is the most effective type.
• Pharmacotherapy
  • Social anxiety disorder
    • First-line agents: SSRIs,; e.g., paroxetine , sertraline or SNRIs, e.g., venlafaxine
    • Alternative agents: benzodiazepines (e.g., clonazepam), pregabalin, phenelzine
  • Performance-only social anxiety disorder: as needed 30–60 minutes before anxiety-inducing event
    • Beta blockers, e.g., propranolol (off-label) ^[19]
    • OR Benzodiazepines, e.g., clonazepam

CBT combined with pharmacotherapy provides more rapid and long-lasting improvement of social anxiety disorder than CBT alone. ^[19]

• 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 ^[22]
  • 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) ^[23][24][25]
    • 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:^[3]

Background ^[26][27][28]

• 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 ^[29]

Clinical features ^[30]

• 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 ^[30][31]

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 diagnoses

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 ^[30]

• 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. ^[32]

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 ^[33]
• Etiology ^[34][35]
  • Alcohol
  • Caffeine
  • Anticonvulsants, opioids, and sedatives
  • Anticholinergics
  • Beta agonists
  • Corticosteroids
  • Amphetamines, cannabis, cocaine, phencyclidine, hallucinogens, and inhalants
• Clinical features ^[3][33][36]
  • 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. ^[37]
  • 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) ^[3]
  • 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 ^[38]
  • 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 ^[37]

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. ^[37]

• 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) ^[3]
  • 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 ^[39]
  • 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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