MD Notes

creation date: 2026-03-09 16:16
tags: Pathologies

Generalized Anxiety Disorder

Background

Definitions

Generalized anxiety disorder (GAD) is a anxiety disorder characterized by persistent, excessive, and unrealistic worry about everyday things.

GAD is highly prevalent and occurs more frequently in females (2:1). The average age of onset is around 30 with a broad range.

Pathogenesis

Genetics
There is a genetic predisposition for the development of GAD which may be common heritability with major depression and the personality trait “neuroticism”.

Neurotransmitter disturbances
GAD may be associated with:

  • Elevated norepinephrine
  • Blunted postsynaptic alpha-2 adrenergic receptor sensitivity
  • Elevated serotonin (associated with somatic anxiety symptoms)

Structural changes and metabolism
There may be associated white matter volume changes within the brain. Additionally, glucose metabolism is altered in the cortex, limbic system, and basal ganglia.

Brain functional MRI have shown greater anticipatory activity in bilateral dorsal amygdala to aversive and neutral pictures suggesting greater emotional responsiveness in GAD.

Cognitive and psychological factors
Individuals with GAD have shown consistent bias in generating negative interpretations of ambiguous material. They may be more vigilant in detecting threatening stimuli.

There is an association with traumatic experiences and other ACEs.

Clinical Presentation

Signs & Symptoms

The characteristic symptom is excessive worry, typically out of proportion to the expected impact of the anticipated event or the object of worry.

Severity fluctuates but the disturbances are chronic (although there may be symptom free periods).

History & Physical Exam

History should assess the frequency, character, and severity of symptoms. This can be made using screening tools such as GAD-7. If indicated, an MSE may be documented.

Physical exam should be targeted to any suspected physical cause of anxiety.

Risk Factors

Diagnosis

Criteria

Diagnosis is made using DSM-5 criteria:

  1. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least six months, about a number of events or activities
  2. The worry is difficult to control
  3. The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past six months). Note: Only one item is required in children.
    • Restlessness or feeling keyed up or on edge
    • Being easily fatigued
    • Difficulty concentrating or mind going blank
    • Irritability
    • Muscle tension
    • Sleep disturbance
  4. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
  5. The disturbance is not attributable to the physiologic effects of a substance (eg, a drug of abuse, a medication) or another medical condition (eg, hyperthyroidism)
  6. The disturbance is not better explained by another mental disorder

Work-up

Screening
Screening is recommended using the GAD-7. A score of ≥10 indicates further assessment (diagnostic interview and MSE).

  • Score 5-9: mild
  • Score 10-14: moderate
  • Score ≥15: severe

Laboratory testing
General screening for underlying medical disorders:

  • CBC
  • Electrolytes and creatinine
  • Thyroid function
  • Urinalysis
  • ECG (if presenting with palpitations)
  • Urine toxicology

Differential

In addition to major depression, several anxiety-related and psychiatric disorders are on the differential:

  • Illness anxiety disorder
  • Panic disorder
  • Adjustment disorder
  • Obsessive-compulsive disorder
  • Substance use disorder

Additionally, nonpathologic anxiety should be differentiated. In contrast to GAD, nonpathologic anxiety:

  • Have minimal or no effect on areas of functioning
  • Have no significant distress

Red Flags / Complications

The primary psychosocial complication is psychological impairment in occupational, social, and household functioning.

Comorbid conditions include other forms of anxiety as well as major depression.

GAD is also associated with:

  • Poor cardiovascular health
  • Coronary heart disease
  • Cardiovascular mortality

Management

General Considerations

The goal of treatment is to reduce symptoms to improve functioning. Thus, patients with mild patients may not need treatment initially if functioning is not significantly impaired.

Depending on patient preference, treatment may consist of pharmacotherapy and/or cognitive-behavioural therapy.

Pharmacotherapy

The first line treatment is SSRIs or SNRIs.

  • Start at lowest dose and titrate up after a week if tolerated

In cases of suboptimal/no response to SRIs, other options include:

  • Buspirone
  • Gabapentin or pregablin

Other alternatives are available if there is a specific symptom to target following partial response (eg. mirtazapine if prominent insomnia)

Cognitive-Behavioural Therapy

CBT is effective as monotherapy or as adjunctive treatment.

References

Tools / Guidelines

MDCalc - GAD-7

Additional Reading