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Generalised anxiety disorder

Definition
  • At least 6 months of excessive worry about everyday issues that is disproportionate to any inherent risk, causing distress, or impairment.
  • The worry is not confined to features of another mental disorder, or as a result of substance abuse or a general medical condition.
  • At least 3 of the following emotional, somatic, and cognitive symptoms are present most of the time:
    • restlessness or nervousness
    • being easily fatigued
    • poor concentration
    • irritability
    • muscle tension
    • sleep disturbance
  • Other common complaints are autonomic in nature, such as sweating, lightheadedness, palpitations, dizziness, and epigastric discomfort. [2] 
  • Anxiety may be 'free-floating' (i.e., not restricted to, or even strongly predominating in, any particular environmental circumstances). [2] 
  • Examples of worries include fears that the patient or a relative will shortly become ill or have an accident.
Risk Factors
  • FHx of anxiety
  • Physical or emotional stress
  • Hx of physical or emotional trauma
  • Depression
  • Other anxiety disorder
  • Female gender
  • Diabetes
Differential diagnosis
  • Panic disorder
    • Characterised by recurrent episodes of sudden onset of anxiety
    • Strong autonomic and physical complaints without the predominant picture of worry. [1]
    • At least 4 symptoms including shortness of breath, palpitations, shakiness, nausea, hot or cold flushes, dizziness, and fear of dying.
    • Panic may exist along with GAD
  • Social phobia 
    • Anxiety or persistent fear is limited to social situations and fear of social scrutiny or embarrassment. [1] 
  • Obsessive-compulsive disorder 
    • Anxiety is directly related to compulsions or obsessions. 
  • Post-traumatic stress disorder 
    • Anxiety is directly related to exposure to reminders of past trauma. 
  • Somatoform disorders 
    • Anxiety is directly related to specific physical complaints. 
    • Thorough medical evaluation shows no basis for physical complaints. 
  • Depression 
    • Inability to feel pleasure with an overall sad or irritable mood. [1] [28] 
  • Substance- or drug-induced anxiety disorder 
    • Anxiety is directly related to exposure to:
      • substance (e.g., caffeine, toxin, alcohol, illicit drug)
      • drug (e.g., salbutamol, theophylline, corticosteroid, antidepressant)
      • herbal medicine (e.g., ma huang, St. John's wort, ginseng, guarana, belladonna).
  • CNS-depressant withdrawal 
    • Anxiety may occur during withdrawal of a substance (e.g., alcohol, opioids, sedative-hypnotics)
    • Characteristic symptoms such as shakiness (i.e., rapid heart rate, fluctuating blood pressure), and, if delirium is present, mental confusion. 
    • Typical signs on are tachypnoea, tachycardia, and disorientation
  • Anorexia nervosa 
    • Anxiety is directly related to a fear of gaining weight. 
    • Body weight <85% of ideal. 
  • Situational anxiety (non-pathological) 
    • Anxiety can be avoided and is more controllable and less pervasive. 
    • Situational worries are less likely to be accompanied by physical symptoms. [1] 
    • Restlessness, fatigue, and other physical symptoms are rarely present.
  • Adjustment disorder 
    • Anxiety occurs temporarily in response to a life stressor and does not persist for more than 6 months after the stressor ends. 
  • Cardiac disease 
    • Anxiety symptoms are predominantly cardiac in nature
    • Palpitations, sensation of rapid heartbeat or skipped heartbeat, dizziness, dyspnoea on exertion, chest pain, and numbness
    • Chest pain is typically exertional.
  • Pulmonary conditions
  • Hyperthyroidism 
    • Weight loss, warm moist skin, heat intolerance, ophthalmopathy, or goitre. 
    • TFTs (increased T4, decreased TSH) can identify primary hyperthyroidism or use of excessive thyroid hormone. 
  • Infections 
    • Anxiety limited to the time period of the infection. 
  • Peptic ulcer disease 
    • Typically, burning epigastric pain which occurs hours after meals or with hunger, relieved by food or antacids. 
  • Crohn's disease 
    • Chronic diarrhoea, weight loss, and right lower quadrant abdominal pain mimicking acute appendicitis. 
    • Perianal lesions including skin tags, fistulae, abscesses, scarring or sinuses. 
  • Irritable bowel syndrome 
    • Alteration of bowel habits associated with pain, and abdominal discomfort, bloating, or distention.
Epidemiology
  • Generalised anxiety disorder (GAD) usually occurs along with other mental disorders. [5] [6] [7] 
    • One study in Europe showed that 76% of people who had more than 1 mental disorder for 12 months had GAD.
  • In the US, GAD has an estimated lifetime prevalence of 5% and a 12-month prevalence of 3%
  • About two thirds of patients diagnosed are female, and more women (55% to 60%) than men are diagnosed in clinical settings. [1]
  • Over half of the people seeking help have an onset in childhood or adolescence.
  • Diagnosis is less common in people over 65 years of age. [9] [10] 
  • A large US epidemiological study found that almost half of people retained the diagnosis over 2 years after diagnosis. [5]
Aetiology
  • No single aetiology exists
  • An increase in minor life stressors, [13] [14] presence of physical or emotional trauma, [15] and genetic factors seem to contribute.
  • A systematic review found that bullying or peer victimisation among youths was associated with an increased incidence. [16] 
  • A review of 35 twin and family studies found a significant association with other anxiety disorders and depression, suggesting a common underlying genetic factor. [18]
  • Abnormality of chromosome 15 has been associated with panic, agoraphobia, social phobia, and joint laxity in families, and with panic disorder in non-familial cases.
    • However, this data is preliminary only
    • Further investigations, including more sophisticated studies of genetic markers, are warranted to substantiate this and identify other genetic factors associated with anxiety disorders. [19]
Clinical features
  • Presence of risk factors
  • Excessive worry for at least 6 months
  • Anxiety not confined to another mental disorder
  • Anxiety not due to medication or substance
  • Muscle tension
  • Sleep disturbance
  • Fatigue
  • Restlessness
  • Irritability
  • Poor concentration
  • Headache
  • Sweating
  • Dizziness
  • GI symptoms
  • Muscle aches
  • Increased heart rate
  • Shortness of breath
  • Trembling
  • Exaggerated startle response
  • Chest pain
Pathophysiology
  • Not clearly understood
  • Studies have identified changes in cerebral blood flow in response to stress
  • Hypervigilance and increased metabolic activity suggest hyperactive brain circuitry. [20]
  • Multiple neurotransmitters involving wide areas of the brain have been implicated in anxiety and other disorders [21] 
    • Including receptors for benzodiazepines, N-methyl-D-aspartate/glutamate, serotonin, and cholecystokinin.
  • Abnormalities in brain corticotrophin-releasing factor secretion in the hypothalamic-pituitary-adrenal axis appear to co-occur with anxiety episodes
    • May adversely affect neurotransmitters and arousal. [22] 
  • The associated heightened vigilance and arousal are associated with insomnia and diurnal fatigue. [23]
Investigations
  • DSM-IV-TR criteria for GAD:
    • At least 6 months of excessive worry about everyday issues that is disproportionate to any inherent risk, causing distress, or impairment.
    • The worry is not confined to features of another mental disorder or as a result of substance abuse or a general medical condition.
    • At least 3 of the following symptoms are present most of the time:
      • restlessness or nervousness, being easily fatigued, poor concentration, irritability, muscle tension, or sleep disturbance. [1] 
  • Tests to rule out other conditions:
Management

a) conservative
  • CBT
  • Psychotherapy
  • Applied relaxation
b) medical
  • Hydroxyzine
  • Benzodiazepines
  • Antidepressants if depression coexists
    • SSRIs, SNRIs, or buspirone are considered the drugs of choice
c) surgical

Prognosis
  • Pharmacotherapy should be given for at least 6 to 8 weeks to determine efficacy, and continued for up to 6 to 12 months if effective. [27]
  • The physician may attempt to taper the medication after this period, monitoring the patient for recurrence of symptoms.
  • With proper treatment, a decrease in symptoms, improved psychosocial functioning, and a reduction in over-utilisation of medical care can be achieved.
  • Generalised anxiety disorder may recur under physical or emotional stress.
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