Generalized anxiety disorder

Diagnosis & Epidemiology - Worry Wart Central

• DSM-5 Criteria: Excessive, uncontrollable worry about various topics, occurring more days than not for ≥6 months.
• Requires ≥3 of the following symptoms (only 1 for children):
  • Restlessness or feeling on edge
  • Easily fatigued
  • Difficulty concentrating
  • Irritability
  • Muscle tension
  • Sleep disturbance
• Epidemiology: Lifetime prevalence ~9%. More common in women (2:1 ratio).

⭐ High-Yield: GAD has a very high comorbidity with other psychiatric disorders, especially Major Depressive Disorder.

Pathophysiology - Brain on Overdrive

• Core Dysregulation: Overactive "anxiety circuit" involving key brain regions.
  • ↑ Amygdala Activity: The brain's "fear center" is hyper-responsive to perceived threats, driving fear.
  • ↓ Prefrontal Cortex (PFC) Control: Ineffective top-down inhibition of the amygdala, leading to uncontrollable worry.
• Neurotransmitter Imbalance:
  • Serotonin & GABA: Dysregulation, particularly ↓ inhibitory GABAergic tone.
  • Norepinephrine: ↑ levels contribute to autonomic symptoms like palpitations and restlessness.

⭐ The bed nucleus of the stria terminalis (BNST) mediates the sustained, anticipatory anxiety of GAD, distinct from the amygdala's role in acute fear.

Clinical Presentation & Workup - The Daily Grind

• Hallmark: Pervasive, difficult-to-control anxiety and worry about multiple domains (e.g., work, health), lasting ≥6 months.
• Associated with ≥3 of the following symptoms:
  • Restlessness or feeling "on edge"
  • Easy fatigability
  • Difficulty concentrating
  • Irritability
  • Muscle tension
  • Sleep disturbance
• Workup:
  • Primarily a clinical diagnosis.
  • Rule out organic causes (hyperthyroidism, substance use) with TSH & urine toxicology.
  • GAD-7 scale helps quantify severity.

⭐ High comorbidity with Major Depressive Disorder is the rule, not the exception; always screen for depression and suicidality.

Differential Diagnosis - Is It Just Worry?

• Medical Conditions: Always rule out organic causes.
  • Hyperthyroidism (check TSH), pheochromocytoma, hypoglycemia, arrhythmias.
• Substance-Induced:
  • Intoxication: Caffeine, stimulants (amphetamines, cocaine).
  • Withdrawal: Alcohol, benzodiazepines, barbiturates.
• Other Psychiatric Disorders:
  • Panic Disorder: Worry is focused on future panic attacks.
  • Social Anxiety Disorder: Worry is specific to social situations.
  • MDD: Overlapping worry/rumination; assess for core depressive sx.

⭐ GAD involves excessive worry about real-life circumstances (finances, health), whereas OCD features ego-dystonic obsessions that are often bizarre or irrational.

Management - Taming the Worry Dragon

• First-Line: SSRIs (e.g., Sertraline) or SNRIs (e.g., Venlafaxine) are initial pharmacotherapy. Cognitive Behavioral Therapy (CBT) is equally first-line.
  • Allow 4-6 weeks for antidepressant efficacy.
  • Benzodiazepines can bridge severe, acute symptoms (⚠️ high dependence risk).
• Second-Line: Switch to a different SSRI/SNRI, or augment with buspirone.

⭐ Cognitive Behavioral Therapy (CBT) demonstrates efficacy comparable to pharmacotherapy and provides durable, long-lasting skills, making it a cornerstone of GAD management.

High-Yield Points - ⚡ Biggest Takeaways

• Chronic, excessive worry about multiple life domains, occurring more days than not for at least 6 months.
• Must have ≥3 associated symptoms: restlessness, fatigue, difficulty concentrating, irritability, muscle tension, or sleep disturbance.
• First-line treatment includes SSRIs (e.g., sertraline) or SNRIs (e.g., venlafaxine), often combined with psychotherapy.
• Cognitive Behavioral Therapy (CBT) is the most effective non-pharmacologic treatment.
• High comorbidity with major depressive disorder.
• Always rule out underlying medical causes (e.g., hyperthyroidism) and substance use.