generalized anxiety disorders

**DSM-5 criteria (adults):** - Excessive anxiety and worry about multiple events or activities, occurring more days than not for ≥6 months. - Worry is difficult to control. - ≥3 of 6 associated symptoms: restlessness/feeling keyed up, easy fatigability, difficulty concentrating/mind going blank, irritability, muscle tension, sleep disturbance. (Children need only 1.) - Causes clinically significant distress or functional impairment. - Not attributable to a substance or medical condition, and not better explained by another psychiatric disorder (e.g., panic disorder, social anxiety, OCD, PTSD).

**Epidemiology and risk factors:** - Lifetime prevalence is about 5-6%. Women are affected about 2x as often as men. - Onset is typically in late adolescence to the 30s, with a chronic, waxing-waning course. - Risk factors: family history (modest heritability), childhood adversity, behavioral inhibition/neuroticism, and female sex. - Comorbid major depression is very common. Other comorbidities include other anxiety disorders and substance use disorders.

**Pathophysiology:** - Dysregulation of the amygdala-prefrontal cortex circuitry, with an overactive fear/threat response. - Decreased GABA-A inhibitory tone and altered serotonin and norepinephrine signaling. - The locus coeruleus (norepinephrine) and raphe nuclei (serotonin) are implicated.

**Clinical features:** - Chronic, free-floating worry that is often out of proportion to actual risk. - Somatic complaints: headaches, GI upset (IBS-like), palpitations, and muscle aches. - Patients often present to primary care with somatic symptoms rather than worry.

**Differential diagnosis (key board distinctions):** - Panic disorder: discrete, abrupt attacks of intense fear with peak symptoms within minutes, plus worry about future attacks. - Social anxiety disorder: fear limited to social or performance situations. - Specific phobia: fear of a specific object or situation. - OCD: obsessions with compulsions. - PTSD/acute stress disorder: follows a traumatic event. - Adjustment disorder with anxiety: within 3 months of an identifiable stressor, lasts <6 months after the stressor ends. - Medical mimics to rule out: hyperthyroidism, pheochromocytoma, hypoglycemia, arrhythmias, and caffeine, stimulant or withdrawal states (alcohol, benzodiazepines). Check TSH and consider a drug screen.

**Treatment:** - First-line: SSRIs (sertraline, escitalopram) or SNRIs (venlafaxine, duloxetine), and/or CBT. Combination therapy is often most effective. - Onset of pharmacologic benefit takes 2-6 weeks. Start low to avoid initial jitteriness. - Buspirone: a 5-HT1A partial agonist. It is non-sedating, has no abuse potential or dependence, and takes 2-4 weeks to work. It is not useful for acute panic. - Benzodiazepines (e.g., lorazepam, diazepam): act on GABA-A to increase the frequency of Cl⁻ channel opening. They give rapid relief but carry risks of dependence, tolerance, sedation, and respiratory depression with alcohol or opioids. Use only short term or as a bridge until SSRIs/SNRIs take effect. - Other options: hydroxyzine, pregabalin (used in some countries), and TCAs/imipramine (less favored). - Beta-blockers (propranolol) help performance anxiety/somatic symptoms but are not first-line for GAD.

**High-yield pearls:** - The 6-month duration is the key differentiator from adjustment disorder and brief anxiety states. - GAD worry spans multiple domains. Social anxiety and phobias are limited to specific triggers. - Choose buspirone when the patient has a history of substance abuse and needs a non-addictive agent. - Benzodiazepine withdrawal can cause seizures, so taper gradually. Flumazenil reverses benzodiazepine overdose.