Generalized anxiety disorder (GAD) is a chronic anxiety disorder characterized by excessive, persistent, and uncontrollable worry about multiple aspects of daily life (health, finances, work, family, minor matters) accompanied by physical symptoms of autonomic hyperarousal and muscle tension. Lifetime prevalence is approximately 5-6% with twice the incidence in women compared to men. Onset is typically in early adulthood (median age 30) but can occur at any age, with chronic course often lasting decades. Pathophysiology involves dysfunction in the amygdala and prefrontal cortex (impaired top-down regulation of fear/worry), serotonergic and noradrenergic dysregulation, GABA receptor dysfunction, HPA axis hyperactivity, and genetic vulnerability (heritability ~30%) with environmental contributors (childhood adversity, traumatic experiences).
DSM-5-TR diagnostic criteria require: (1) excessive anxiety and worry about a number of events or activities for more days than not for >=6 months; (2) the individual finds it difficult to control the worry; (3) anxiety and worry are associated with >=3 of 6 symptoms in adults (only 1 needed in children): restlessness or feeling keyed up/on edge, easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, sleep disturbance (difficulty falling/staying asleep, restless unsatisfying sleep); (4) anxiety, worry, or physical symptoms cause clinically significant distress or impairment; (5) symptoms are not attributable to substances or medical conditions; (6) symptoms are not better explained by another mental disorder. Common comorbidities include major depression (60%), other anxiety disorders, substance use disorders, and somatic symptom disorders.
Treatment is multimodal and individualized: first-line pharmacotherapy includes selective serotonin reuptake inhibitors (escitalopram 10-20 mg, sertraline 50-200 mg, paroxetine 20-50 mg), serotonin-norepinephrine reuptake inhibitors (venlafaxine XR 75-225 mg, duloxetine 60-120 mg), and buspirone 15-60 mg/day (5-HT1A partial agonist, non-sedating, non-addictive but slow onset 2-4 weeks); benzodiazepines (lorazepam, alprazolam, clonazepam) provide rapid relief but reserved for short-term/acute severe anxiety due to dependence and rebound risk; pregabalin 150-600 mg/day approved in Europe and effective. Cognitive behavioral therapy (CBT) is the most evidence-based psychotherapy with components including psychoeducation, cognitive restructuring (identifying/challenging catastrophic worry), worry exposure, problem-solving training, and applied relaxation; mindfulness-based stress reduction (MBSR) and acceptance and commitment therapy (ACT) also effective. Adjunctive interventions include exercise, sleep hygiene, caffeine reduction, mindfulness meditation, and yoga. Refractory GAD may require augmentation with atypical antipsychotics (quetiapine), gabapentin, or hydroxyzine. Treatment duration typically 12+ months after symptom remission to reduce relapse risk.