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.