Behavioral Health

Generalized anxiety disorder: diagnosis and management

Clinical Overview and When to Suspect Generalized Anxiety Disorder

— Lifetime prevalence ~5–6% in US adults; 2:1 female-to-male predominance

— Median age of onset ~30 years, but onset can occur from adolescence through late life

— High comorbidity with major depression (~60%), other anxiety disorders, substance use, and chronic medical illness (IBS, migraine, CAD)

— Frequent primary care visits for vague somatic complaints: fatigue, insomnia, muscle tension, headaches, GI upset, palpitations

— "Worrier" personality, catastrophizing about routine matters, sleep-onset insomnia from racing thoughts

— Polypharmacy seekers, frequent reassurance-seeking, repeated negative workups

— Comorbid hypertension or IBS flares triggered by stress

— Self-rated 7-item questionnaire; score 0–21

— 5 = mild, 10 = moderate, 15 = severe; ≥10 is the typical treatment threshold

— USPSTF (2023) recommends screening all adults <65 for anxiety disorders (Grade B)

— Dysregulation of amygdala–prefrontal circuits; reduced GABAergic tone; serotonergic and noradrenergic dysregulation

— Genetic heritability ~30%; gene–environment interaction with early adversity

Board pearl: Distinguish GAD from normal worry by three features: excessive intensity, difficulty controlling it, and functional impairment with somatic symptoms for ≥6 months. A stem describing a businesswoman who worries "constantly" about minor work issues, has neck tension, insomnia, and a normal TSH/ECG is classic GAD — not panic disorder (no discrete attacks) and not adjustment disorder (no identifiable stressor within 3 months).

Definition: Generalized anxiety disorder (GAD) is excessive, difficult-to-control worry about multiple domains (work, health, family, finances) occurring more days than not for ≥6 months, accompanied by somatic and cognitive symptoms causing functional impairment.

Epidemiology:

When to suspect on a Step 3 stem:

Screening tool — GAD-7:

Pathophysiology snapshot:

Presentation Patterns and Key History

— Restlessness or feeling keyed up

— Irritability

— Muscle tension

— Fatigue (easy fatigability)

— Concentration difficulty / mind going blank

— Sleep disturbance (onset or maintenance)

— Mnemonic: "WATCHERS" (Worry, Anxiety, Tension, Concentration, Hyperarousal, Energy loss, Restlessness, Sleep)

— Timeline: symptoms must predate or be independent of substance use, medication changes, or medical illness

— Domains of worry: typically ≥2 (family, finances, work, health) — single-domain worry suggests specific phobia or illness anxiety

— Triggers: worry is often free-floating, not tied to discrete cues (vs. panic, PTSD, OCD)

— Functional impact: missed work, strained relationships, avoidance, decreased productivity

— Substance review: caffeine intake (>400 mg/day), stimulants, decongestants, albuterol, levothyroxine overreplacement, alcohol/benzo withdrawal

— Sleep history: initial insomnia from rumination is classic

— Suicide screen: always — comorbid depression raises risk

— Chest pain with normal ECG/troponin

— Chronic headaches, neck/shoulder pain

— IBS-type GI symptoms

— Dizziness, paresthesias, globus sensation

— Frequent ED visits for "near-syncope"

— Perfectionism, reassurance-seeking, school refusal, somatic complaints (stomachaches before school), "old beyond their years"

Key distinction: GAD worry is chronic and pervasive, panic disorder presents with discrete paroxysmal attacks, social anxiety is performance/scrutiny-triggered, and OCD features intrusive ego-dystonic thoughts with compulsions. A patient who worries continuously about "everything" without rituals or attacks → GAD. Always document the 6-month duration explicitly to lock in the diagnosis on the boards.

Core symptom cluster (DSM-5-TR criteria): excessive worry ≥6 months plus ≥3 of 6 symptoms (only 1 required in children):

High-yield history elements:

Common somatic chief complaints disguising GAD:

Pediatric/adolescent presentation:

Physical Exam Findings (and Autonomic Assessment)

— Tense posture, furrowed brow, fidgeting, hand-wringing, leg-bouncing

— Sighing respirations, frequent throat clearing

— Difficulty sitting still during the encounter; may pace

— Mild resting tachycardia (often 90–110), borderline hypertension (white-coat amplification)

— Tachypnea; occasional hyperventilation with paresthesias and lightheadedness

— Normothermic — fever should redirect workup

— Dry mouth from sympathetic tone

— Trapezius and paraspinal tenderness (muscle tension is core symptom)

— Palpate thyroid carefully — must exclude goiter/nodule before attributing tremor and tachycardia to anxiety

— Tachycardia without murmur; benign systolic flow murmur possible

— Clear lungs; sighing breaths

— Cool, clammy palms; mild fine postural tremor (sympathetic, not resting)

— Symmetric brisk reflexes possible

— No focal deficits — focal findings demand neurologic workup

— Mental status: anxious affect, ruminative thought content, intact reality testing, no psychosis

— Exophthalmos, lid lag, thyroid bruit → hyperthyroidism

— Episodic paroxysmal HTN with diaphoresis, headache → pheochromocytoma

— Orthostatic hypotension with tachycardia → consider POTS, dehydration, autonomic dysfunction

— Pinpoint or dilated pupils, track marks, slurred speech → substance use

— Murmur of MVP/aortic stenosis or irregular rhythm → cardiac workup

Step 3 management: Always obtain an orthostatic BP and HR, perform a focused thyroid exam, and screen for substance use before committing to a GAD diagnosis. Step 3 stems frequently bury hyperthyroidism, pheochromocytoma, or stimulant misuse inside an "anxious patient" presentation — the exam clue (thyroid nodule, paroxysmal HTN, dilated pupils) tells you to redirect testing rather than start an SSRI.

General appearance:

Vital signs:

HEENT/neck:

Cardiopulmonary:

Neurologic:

What you should NOT find (red flags that argue against pure GAD):

Diagnostic Workup — Initial Labs and Baseline Studies

— TSH (± free T4) — must rule out hyperthyroidism in any new anxiety presentation

— CBC — anemia can mimic fatigue/palpitations

— CMP — glucose (hypoglycemia mimics panic), electrolytes, hepatic/renal baseline before SSRI/SNRI

— Fasting glucose / HbA1c if hypoglycemic spells

— Urine toxicology when stimulant or substance use is suspected

— Pregnancy test (β-hCG) in reproductive-age women before prescribing

— Palpitations, chest pain, syncope, family history of sudden death

— Baseline before citalopram/escitalopram in patients >60, with cardiac disease, or on QT-prolonging meds (citalopram max 20 mg if >60 or hepatic impairment)

— Before TCAs (rare in GAD)

— Episodic spells with HTN, diaphoresis, headache → plasma free metanephrines for pheochromocytoma

— Diarrhea, flushing → 5-HIAA for carcinoid

— Tremor + weight loss + heat intolerance → confirm hyperthyroid panel

— New-onset anxiety after age 40 with no prior history → broaden medical workup (cardiac, endocrine, neurologic, occult malignancy)

— GAD-7 — primary diagnostic aid and treatment-response tracker

— PHQ-9 — co-administer to screen depression (60% comorbidity)

— AUDIT-C — alcohol use screen

— Hamilton Anxiety Rating Scale (HAM-A) — clinician-rated, used in research

Board pearl: New-onset anxiety in a patient >40 years old with no prior psychiatric history is a red-flag stem — the answer is rarely "start sertraline." Look for organic cause: hyperthyroidism, pheochromocytoma, arrhythmia, early dementia, occult cancer, or medication side effect. The Step 3 vignette often hides one abnormal vital sign or lab — anchor on it before prescribing.

GAD is a clinical diagnosis — no lab confirms it. Labs serve to exclude mimics and to baseline before pharmacotherapy.

Targeted initial labs (driven by history/exam):

ECG indications:

When to extend the workup:

Validated screening/severity tools:

Diagnostic Workup — Advanced or Confirmatory Evaluation

— Recurrent palpitations with abnormal baseline ECG → ambulatory Holter or event monitor to exclude SVT, AF, WPW

— Exertional symptoms → stress testing

— Syncope with anxiety → tilt-table, echocardiogram

— Borderline TSH with strong clinical suspicion → free T4, free T3, TSI/TRAb

— Paroxysmal HTN spells → 24-hour urine metanephrines if plasma test equivocal

— Cushingoid features → late-night salivary cortisol or dexamethasone suppression

— Focal deficits, new headache pattern, seizure-like spells → MRI brain

— Cognitive complaints in older adults → formal cognitive testing (MoCA), as anxiety can be a prodrome of neurocognitive disorder

— Loud snoring, witnessed apneas, daytime somnolence → polysomnography to rule out OSA (often presents as anxiety/irritability)

— Structured interview (MINI, SCID) in ambiguous cases

— Reassess for bipolar disorder before starting antidepressant — SSRIs can precipitate mania

— Screen for PTSD (PCL-5), OCD (Y-BOCS), social anxiety (LSAS)

— Not routinely recommended; consider only after multiple failed trials

— CYP2D6/2C19 status may guide dosing of some SSRIs

— GAD-7 at baseline, 4–6 weeks, and at each med adjustment

— Sheehan Disability Scale to quantify functional impairment

Key distinction: Step 3 frequently tests GAD vs. early hyperthyroidism vs. pheochromocytoma vs. cardiac arrhythmia. The discriminator is episodic vs. continuous symptoms — GAD worry is persistent and cognitive-driven, while pheochromocytoma and arrhythmia produce discrete, autonomic-dominant paroxysms with measurable abnormalities (metanephrines, ECG capture).

There is no confirmatory test for GAD — diagnosis remains DSM-5-TR criteria-based. Advanced workup is reserved for atypical features or treatment-refractory cases.

When to pursue advanced cardiac workup:

When to pursue advanced endocrine workup:

Neurologic workup:

Sleep evaluation:

Psychiatric formulation:

Pharmacogenomic testing:

Severity & functional measures to track over time:

Risk Stratification and First-Line Management Logic

— Mild (5–9): psychoeducation, lifestyle modification, watchful waiting, self-help CBT apps; pharmacotherapy not required

— Moderate (10–14): offer CBT or pharmacotherapy (SSRI/SNRI) — patient preference drives choice; combine if impairment significant

— Severe (≥15) or marked impairment: combination CBT + pharmacotherapy is most effective

— Discuss expected onset of pharmacologic benefit (4–6 weeks, full response 8–12 weeks)

— Discuss CBT logistics (12–16 weekly sessions, cost, availability, telehealth options)

— Address patient concerns about "dependence" — SSRIs/SNRIs are not addictive but require taper

— Aerobic exercise ≥150 min/week — moderate effect size

— Sleep hygiene — consistent schedule, screen reduction

— Caffeine reduction to <200 mg/day; eliminate energy drinks

— Alcohol limitation — alcohol worsens anxiety via withdrawal rebound

— Mindfulness-based stress reduction (MBSR) — moderate evidence

— CBT is first-line, including cognitive restructuring + exposure to worry

— Applied relaxation, mindfulness-based CBT, acceptance and commitment therapy (ACT) also effective

— Digital CBT (e.g., FDA-cleared apps) reasonable when access limited

— Moderate-to-severe symptoms

— Failed psychotherapy trial

— Patient preference

— Significant comorbid depression

Step 3 management: For a patient with GAD-7 of 16, insomnia, and impaired work function, the best initial answer is start an SSRI (e.g., escitalopram 10 mg) AND refer to CBT — not benzodiazepines, not "lifestyle changes alone." If the stem offers only one option, SSRI beats benzodiazepine because of dependence/falls risk, especially in elderly patients.

Stratify severity using GAD-7:

Shared decision-making elements:

Lifestyle interventions (evidence-supported adjuncts):

Psychotherapy options:

Pharmacotherapy initiation triggers:

Pharmacotherapy — First-Line Drug Regimen

— Escitalopram 10 mg daily (max 20 mg; 10 mg cap if >60 or hepatic impairment)

— Sertraline 25–50 mg daily, titrate to 50–200 mg

— Paroxetine 20–50 mg — effective but anticholinergic, weight gain, avoid in elderly and pregnancy (Category D)

— Duloxetine 30 mg → 60 mg (max 120 mg); helpful when comorbid neuropathic pain or fibromyalgia

— Venlafaxine XR 37.5 mg → 75–225 mg; monitor BP (dose-dependent HTN >150 mg)

— "Start low, go slow" — anxious patients are sensitive to activation/jitteriness in first 1–2 weeks

— Counsel about transient worsening of anxiety, GI upset, insomnia, sexual dysfunction

— Black-box warning: increased suicidality in patients <25; document discussion

— Reassess at 2 weeks (tolerability) and 4–6 weeks (efficacy via GAD-7)

— Continue effective dose for ≥12 months after remission before considering taper

— Buspirone 7.5 mg BID → 15–30 mg BID — non-sedating, no dependence, slow onset (2–4 weeks); useful as augmentation or in patients avoiding SSRIs

— Pregabalin 150–600 mg/day (off-label in US; first-line in Europe) — rapid onset, watch for sedation and misuse potential

— Hydroxyzine 25–50 mg up to QID — short-term, non-addictive, sedating

— Mirtazapine when insomnia/weight loss prominent

— Short-term bridge only (2–4 weeks) while SSRI takes effect

— Avoid in elderly, substance use history, OSA, pregnancy

— Lorazepam or clonazepam preferred over alprazolam (less rebound)

Board pearl: Avoid benzodiazepines as monotherapy or long-term in GAD — Step 3 punishes this choice. The correct sequence: SSRI/SNRI + CBT first, buspirone or hydroxyzine as non-addictive adjuncts, benzodiazepine only as a brief bridge with a documented taper plan. Discontinue SSRI gradually over 2–4 weeks to prevent discontinuation syndrome (flu-like, paresthesias, "brain zaps").

First-line agents — SSRIs and SNRIs (equivalent efficacy):

Initiation principles:

Second-line / adjunctive agents:

Benzodiazepines:

Expanded Pharmacology — Augmentation, Switching, and Refractory GAD

— <50% reduction in GAD-7 after 8–12 weeks at therapeutic dose

— Persistent functional impairment despite tolerability

— Step 1: Confirm adherence, adequate dose, adequate duration; reassess diagnosis (missed bipolar, substance use, OSA, hyperthyroid)

— Step 2: Optimize dose of current SSRI/SNRI to maximum tolerated

— Step 3: Switch within class (e.g., escitalopram → sertraline) or cross to SNRI (sertraline → duloxetine/venlafaxine)

— Step 4: Augment with buspirone, pregabalin, or hydroxyzine

— Step 5: Consider atypical antipsychotic augmentation (quetiapine XR 50–300 mg has evidence) — weigh metabolic risk; usually requires psychiatry referral

— Taper outgoing SSRI by 25–50% every 1–2 weeks while introducing new agent

— Avoid combining serotonergic agents at full dose — serotonin syndrome risk (with tramadol, linezolid, MAOIs, triptans, St. John's wort)

— Highest with paroxysmal and venlafaxine (short half-life)

— Symptoms: dizziness, flu-like illness, paresthesias, sleep disturbance, irritability, "brain zaps"

— Resolves within days of resuming or slowing taper; consider fluoxetine bridge for severe cases

— Fluoxetine/paroxetine: potent CYP2D6 inhibitors → ↑levels of metoprolol, TCAs, codeine ineffective

— Fluvoxamine: CYP1A2 inhibitor → toxicity with theophylline, clozapine

— SSRI + NSAID or anticoagulant → ↑GI bleed risk (consider PPI)

— SSRI + diuretic → SIADH/hyponatremia, especially in elderly

— Continue ≥12 months after remission; 24+ months if recurrent or severe

— Taper over 4+ weeks, longer if on >6 months

Step 3 management: For a patient failing escitalopram 20 mg after 12 weeks: the best next step is switch to venlafaxine or duloxetine rather than add a benzodiazepine. Always check adherence, dose, duration, and diagnosis before declaring treatment failure.

Defining inadequate response:

Stepwise approach to partial/non-response:

Cross-tapering tips:

Discontinuation syndrome management:

Drug interactions to memorize:

Maintenance and taper:

Special Populations — Elderly and Renal/Hepatic Impairment

— Prevalence ~7%; often underdiagnosed (somatic complaints, comorbid depression, dementia)

— Distinguish from early neurocognitive disorder — anxiety can be a prodrome

— Screen for medical mimics (thyroid, cardiac, COPD, polypharmacy-induced)

— Escitalopram (max 10 mg) or sertraline — fewer interactions, well-tolerated

— Avoid paroxetine (anticholinergic, falls, Beers list)

— Avoid benzodiazepines — Beers criteria; increased falls, fractures, delirium, cognitive decline

— Buspirone is a reasonable non-sedating adjunct

— Hydroxyzine also on Beers list (anticholinergic) — minimize use

— Hyponatremia (SIADH) — check sodium at 2–4 weeks after SSRI initiation, especially with thiazide co-administration

— Falls and bone density — SSRIs ↑fracture risk

— QT prolongation — citalopram >20 mg contraindicated >60

— Bleeding risk if on antiplatelet/anticoagulant

— Sertraline and escitalopram require no dose adjustment in mild-moderate CKD

— Venlafaxine: reduce dose 25–50% in CrCl <30; avoid in dialysis when possible

— Duloxetine: avoid if CrCl <30

— Paroxetine, fluoxetine: reduce dose in severe renal impairment

— Pregabalin: dose by CrCl

— Escitalopram: max 10 mg in hepatic impairment

— Sertraline: reduce dose or extend dosing interval in moderate hepatic disease

— Duloxetine: contraindicated in any hepatic impairment or heavy alcohol use

— Venlafaxine: reduce dose 50%

Board pearl: In a 78-year-old with new anxiety, insomnia, and a creatinine of 1.6, the safest first-line agent is sertraline or low-dose escitalopram. Never pick lorazepam, alprazolam, paroxetine, or duloxetine as the answer in a frail elderly stem. Always recheck sodium at 2–4 weeks — SIADH is the classic Step 3 trap.

Geriatric GAD (>65 years):

Preferred agents in elderly:

Geriatric-specific monitoring:

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Postpartum, and Pediatrics

— Prevalence ~8–10%; untreated anxiety associated with preterm birth, low birth weight, postpartum depression

— Shared decision-making essential — weigh maternal benefit vs. fetal exposure

— Psychotherapy (CBT) is first-line in mild-moderate cases

— Sertraline is the preferred SSRI (low placental transfer, extensive safety data, lowest milk-to-plasma ratio for lactation)

— Escitalopram, citalopram acceptable alternatives

— Avoid paroxetine — associated with cardiac malformations (Ebstein anomaly historical concern); FDA Category D

— Benzodiazepines: avoid in 1st trimester (cleft palate risk debated); avoid near delivery (neonatal sedation, withdrawal)

— Persistent pulmonary hypertension of the newborn (PPHN) — small absolute risk increase with SSRIs late pregnancy

— Neonatal adaptation syndrome — transient jitteriness, feeding difficulty, respiratory distress; self-limited

— Do not abruptly discontinue SSRI before delivery — relapse risk outweighs neonatal effects

— Screen with EPDS at postpartum visits; GAD often overlaps with postpartum depression

— Sertraline preferred during breastfeeding

— Lifetime prevalence ~3% in adolescents

— DSM-5 requires only 1 of 6 somatic symptoms (vs. 3 in adults)

— CBT is first-line monotherapy; combination with SSRI for moderate-severe cases (CAMS trial: CBT + sertraline > either alone)

— FDA-approved SSRIs for pediatric anxiety: duloxetine (≥7 yrs for GAD); escitalopram/sertraline used off-label

— Black-box suicidality warning — weekly monitoring first 4 weeks, biweekly through week 12

— Involve school, parents; assess for bullying, learning disorder, family stress

Key distinction: Sertraline = safest in pregnancy and lactation; paroxetine = avoid in pregnancy; duloxetine = FDA-approved for pediatric GAD. For a pregnant patient with severe GAD already stable on sertraline, continue the medication — abrupt discontinuation triples relapse risk in the peripartum period.

GAD in pregnancy:

Preferred medications in pregnancy:

Third-trimester considerations:

Postpartum:

Pediatric and adolescent GAD:

Complications and Adverse Outcomes

— Major depressive disorder — 60% lifetime comorbidity; doubles disability

— Substance use disorders — alcohol (self-medication), benzodiazepine misuse, cannabis

— Suicidality — increased risk especially with comorbid depression or substance use

— Progression to panic disorder, agoraphobia, social anxiety

— Cardiovascular: chronic sympathetic activation linked to hypertension, CAD, and increased cardiac mortality; GAD independently predicts MI recurrence post-ACS

— GI: worsened IBS, functional dyspepsia, GERD

— Pain: chronic tension headaches, migraine amplification, fibromyalgia overlap

— Endocrine/metabolic: elevated cortisol, insulin resistance, weight changes

— Immune: chronic stress linked to impaired wound healing and infection susceptibility

— Reduced workplace productivity ("presenteeism"), increased disability claims

— Healthcare overutilization — repeated ED visits, unnecessary imaging

— Social withdrawal, relationship strain

— SSRI/SNRI: sexual dysfunction (30–50%), GI upset, weight gain (paroxetine), hyponatremia, bleeding, serotonin syndrome

— Benzodiazepines: dependence (within weeks), tolerance, cognitive impairment, falls, MVCs, respiratory depression with opioids/alcohol, paradoxical disinhibition in elderly

— Pregabalin/gabapentin: sedation, edema, misuse potential, withdrawal seizures

— Discontinuation syndrome from abrupt SSRI/SNRI cessation

— Polypharmacy with multiple sedatives

— Concurrent opioid use → respiratory depression risk (FDA boxed warning on benzo + opioid combo)

Board pearl: Patients with GAD post-MI have worse cardiac outcomes — treat the anxiety as part of secondary cardiovascular prevention. Sertraline is the preferred SSRI in coronary disease (SADHART data). On Step 3, anxiety in a cardiac patient is a treatment indication, not a "softer" issue to defer.

Psychiatric complications:

Medical/somatic complications:

Functional and occupational impact:

Treatment-related adverse outcomes:

Safety events specific to GAD population:

When to Escalate Care — Consult or Inpatient Triage

— Diagnostic uncertainty (rule out bipolar, OCD, PTSD, psychosis)

— Treatment-resistant GAD — failure of ≥2 adequate SSRI/SNRI trials

— Severe functional impairment, disability

— Pregnancy/postpartum with severe symptoms requiring medication

— Pediatric GAD with moderate-severe symptoms or suicidality

— Comorbid substance use disorder requiring integrated care

— Need for benzodiazepine taper in long-term users

— All patients with moderate-severe GAD should be offered CBT referral; co-locate care when possible

— Active suicidal ideation with plan/intent or recent attempt

— Suicidality with disorganized thinking or severe agitation

— Inability to maintain self-care or safety

— Severe comorbid substance use requiring detox

— Catatonia or psychotic features (suggests alternate diagnosis)

— Acute chest pain with abnormal ECG/troponin → cardiology

— Confirmed hyperthyroidism → endocrine

— Pheochromocytoma workup positive → endocrine surgery

— New focal neurologic findings → neurology + imaging

— Sleep medicine for OSA when suspected

— Cardiology if QT prolongation limits SSRI choice

— Pain medicine for comorbid chronic pain

— C-SSRS (Columbia Severity Scale) — standard in EDs and primary care

— Document plan, intent, access to lethal means; counsel on firearm/medication safety

CCS pearl: If a CCS-style anxiety case develops active suicidal ideation with plan, the correct sequence is assess access to lethal means → 1:1 observation → psychiatric evaluation → involuntary hold if patient refuses voluntary admission and meets criteria. Do not discharge home from the office.

Outpatient management is appropriate for the vast majority of GAD patients — escalation is the exception.

Psychiatry referral indications:

Therapy referral:

Emergency/inpatient psychiatric admission criteria:

Medical escalation triggers (rule out organic cause):

Special consults:

Suicide risk assessment tools:

Key Differentials — Other Anxiety and Mood Disorders

— Discrete paroxysmal attacks peaking within 10 minutes — palpitations, dyspnea, choking, derealization, fear of dying

— Worry is about having attacks ("anticipatory anxiety"), not about life domains

— Treatment overlap (SSRI + CBT) but distinct presentation

— Fear of scrutiny/embarrassment in social or performance situations

— Avoidance of specific contexts; physiologic symptoms triggered by social exposure

— First-line: SSRI + CBT; propranolol PRN for performance subtype

— Single-stimulus fear (flying, heights, spiders, blood-injection-injury)

— Treatment: exposure therapy

— Intrusive ego-dystonic thoughts (obsessions) + repetitive compulsions that neutralize anxiety

— Higher-dose SSRIs (e.g., fluoxetine 60–80 mg) + ERP-based CBT

— Identifiable traumatic event + intrusion, avoidance, negative cognition/mood, hyperarousal

— Re-experiencing (flashbacks, nightmares) is the key discriminator

— Sertraline, paroxetine FDA-approved; trauma-focused CBT, EMDR

— Onset within 3 months of identifiable stressor; resolves within 6 months of stressor cessation

— Does not meet full GAD criteria; treat with brief psychotherapy

— Anhedonia, low mood, neurovegetative symptoms dominate

— GAD and MDD frequently coexist — SSRI/SNRI treats both

— Anxiety is common but mood episodes (mania/hypomania) define

— Screen with MDQ before starting SSRI — antidepressant monotherapy can precipitate mania

Key distinction: GAD = chronic, multi-domain, free-floating worry. Panic = paroxysmal autonomic surges. Social anxiety = scrutiny-triggered. OCD = obsessions + compulsions. PTSD = post-trauma re-experiencing. Adjustment = <6 months post-stressor. On Step 3, the time course and trigger pattern usually nail the diagnosis.

Panic disorder:

Social anxiety disorder:

Specific phobia:

Obsessive-compulsive disorder:

PTSD:

Adjustment disorder with anxiety:

Major depressive disorder:

Bipolar disorder:

Key Differentials — Medical and Substance-Induced Mimics

— Hyperthyroidism — tremor, heat intolerance, weight loss, tachycardia, lid lag; check TSH

— Pheochromocytoma — paroxysmal HTN, headache, diaphoresis, palpitations; plasma metanephrines

— Hypoglycemia — adrenergic surge with tremor, sweating, anxiety; especially in diabetics on insulin/sulfonylureas

— Cushing syndrome — anxiety, depression, central obesity, striae

— Carcinoid syndrome — flushing, diarrhea, wheezing; 5-HIAA

— Arrhythmias (SVT, AF, WPW) — palpitations; Holter monitor

— Mitral valve prolapse — mid-systolic click, palpitations

— Acute MI / unstable angina — atypical presentation in women, diabetics

— PE — dyspnea, tachycardia, anxiety; check D-dimer/CTPA when suspicious

— COPD/asthma exacerbation — dyspnea-driven panic

— Obstructive sleep apnea — fatigue, irritability, morning headaches, anxiety

— Temporal lobe epilepsy — episodic fear, déjà vu; EEG

— Vestibular disorders — dizziness mistaken for anxiety

— Early dementia — anxiety as prodromal feature

— Intoxication: caffeine, cocaine, methamphetamine, MDMA, cannabis (paradoxical), albuterol, decongestants, levothyroxine excess, corticosteroids

— Withdrawal: alcohol, benzodiazepines, opioids, nicotine, cannabis

— Check medication list: albuterol, theophylline, pseudoephedrine, stimulants for ADHD, levothyroxine, corticosteroids

— SSRI-induced akathisia in first weeks

— Antipsychotic-induced akathisia

— Interferon, isotretinoin, varenicline (mood effects)

Step 3 management: A 45-year-old with new-onset "anxiety," 10-lb weight loss, fine tremor, and HR 110 = check TSH before prescribing sertraline. A patient with episodic HTN to 210/120 with headache and diaphoresis = plasma metanephrines, not an SSRI. Always rule out organic mimics in atypical presentations — especially new-onset anxiety after age 40.

Endocrine causes:

Cardiopulmonary causes:

Neurologic causes:

Substance-induced anxiety:

Iatrogenic:

Secondary Prevention, Maintenance, and Long-Term Plan

— Continue effective SSRI/SNRI for at least 12 months after remission (GAD-7 <5)

— 24+ months or indefinite if: recurrent episodes, severe baseline impairment, residual symptoms, significant comorbid depression

— Relapse risk after discontinuation is 30–50% within 12 months

— Reduce by 25% every 2–4 weeks; longer tapers for long-term users or short-half-life agents (paroxetine, venlafaxine)

— Counsel on discontinuation syndrome symptoms; instruct to resume previous dose if severe

— Time tapers to low-stress periods (avoid major life transitions)

— Booster CBT sessions every 1–3 months sustain gains

— Self-monitoring with GAD-7 quarterly

— Regular aerobic exercise ≥150 min/week

— Sleep: 7–9 hours, consistent schedule

— Limit caffeine to <200 mg/day; eliminate alcohol/cannabis as self-medication

— Mindfulness practice 10–20 min/day

— Social connection — isolation is a relapse driver

— Identify personal early warning signs (sleep loss, rumination, irritability, somatic symptoms)

— Pre-arranged action plan: contact primary care/therapist, re-initiate CBT skills, consider medication resumption

— Maintain therapist relationship for booster sessions

— Collaborative care model (PCP + behavioral health specialist + care manager) is evidence-based and reimbursable via CoCM CPT codes

— Use of measurement-based care (repeat GAD-7) is standard of care

Step 3 management: A patient in stable remission for 14 months on sertraline asks to stop. Correct approach: discuss relapse risk, plan a gradual taper over 4–8 weeks, schedule follow-up at 4 and 12 weeks post-taper, and instruct on warning signs. Don't stop abruptly, and don't refuse the request outright.

Duration of pharmacotherapy:

Tapering principles:

Maintenance psychotherapy:

Lifestyle pillars to reinforce:

Relapse prevention plan:

Health systems integration:

Follow-Up, Monitoring Parameters, and Counseling

— Week 1–2: phone or in-person tolerability check (especially patients <25 for suicidality; activation/jitteriness)

— Week 4: in-person — partial response expected; repeat GAD-7

— Week 6–8: assess efficacy; titrate dose if GAD-7 reduction <50%

— Week 12: evaluate full response; document remission (GAD-7 <5)

— Maintenance: every 3 months once stable; annually after long-term stability

— Sodium at 2–4 weeks in elderly or those on diuretics (SIADH)

— BP monthly with venlafaxine titration (dose-dependent HTN >150 mg)

— ECG at baseline and after dose changes for citalopram in at-risk patients

— Pregnancy test before initiation in reproductive-age women

— LFTs as clinically indicated with duloxetine

— GAD-7 every visit — primary response metric

— PHQ-9 quarterly to monitor comorbid depression

— Sheehan Disability Scale for functional outcomes

— Track sleep, work productivity, social functioning qualitatively

— Adherence reinforcement — most early "failures" are nonadherence

— Side effect management (sexual dysfunction, GI, sleep)

— Substance use re-screen (AUDIT-C annually)

— Suicide risk re-screen with C-SSRS

— Lifestyle reinforcement

— Written information on expected timeline, side effects, discontinuation syndrome

— CBT workbook or app (e.g., FDA-cleared digital therapeutics)

— Crisis hotline numbers (988) and safety planning

Board pearl: Measurement-based care with serial GAD-7 is the Step 3 standard — vague "patient feels better" is not adequate. If GAD-7 has not dropped by ≥50% at 8–12 weeks at therapeutic dose, switch or augment. Document the score in the chart at every visit.

Follow-up cadence after medication initiation:

Lab monitoring:

Symptom tracking:

Counseling content at each visit:

Patient education materials:

Ethical, Legal, and Patient Safety Considerations

— Discuss black-box warning for suicidality in patients <25 — document explicitly

— Discuss sexual side effects, discontinuation syndrome, pregnancy implications

— Discuss off-label use (pregabalin, quetiapine) when applicable

— Mental health records have enhanced protections under HIPAA in most states

— Adolescents: state laws vary on minor consent for mental health treatment; many states permit ages 12+ to consent independently

— Disclose limits of confidentiality at initiation: harm to self, harm to others, abuse of vulnerable persons

— Suspected child, elder, or dependent adult abuse must be reported regardless of patient confidentiality preferences

— Tarasoff duty to warn/protect identifiable third parties when patient makes credible threats (state-dependent specifics)

— Document suicide assessment with C-SSRS

— Counsel on firearm safety, medication lock boxes, limiting pill quantities dispensed if elevated risk

— Safety planning intervention is evidence-based and required

— Counsel about sedation from benzodiazepines, hydroxyzine, pregabalin — avoid driving until tolerance assessed

— Certain occupations (pilots, commercial drivers) have regulatory restrictions on psychotropic use

— GAD itself rarely impairs decisional capacity

— Involuntary hold criteria require danger to self/others or grave disability — anxiety alone does not meet

— Hospital discharge is a high-risk period — ensure outpatient follow-up within 7 days, medication reconciliation, and clear taper plans for any benzodiazepines started inpatient

— Communicate diagnosis and treatment plan to PCP at handoff

— Address cultural and racial disparities in anxiety diagnosis and treatment

— Use culturally informed assessment tools when possible

Step 3 management: A patient discharged on a new benzodiazepine prescription must have a documented taper plan, follow-up within 7 days, and counseling on driving and falls — these are testable patient-safety expectations on transitions of care.

Informed consent for pharmacotherapy:

Confidentiality:

Mandatory reporting:

Suicide risk and means restriction:

Driving and occupational safety:

Capacity and involuntary care:

Transition-of-care risk:

Stigma and equity:

High-Yield Associations and Rapid-Fire Clinical Facts

— GAD + MDD = 60% — treat with single SSRI/SNRI

— GAD + IBS common — duloxetine helps both anxiety and visceral pain

— GAD + chronic pain/fibromyalgia — duloxetine is dual-purpose

— GAD post-MI worsens cardiac outcomes — sertraline preferred (SADHART)

— GAD + OSA — anxiety often improves with CPAP

— Sertraline = safest in pregnancy, lactation, post-MI

— Escitalopram = max 10 mg if >60 or hepatic impairment

— Paroxetine = avoid in pregnancy and elderly (anticholinergic, weight gain, sedation)

— Venlafaxine = dose-dependent HTN >150 mg

— Duloxetine = avoid if CrCl <30 or hepatic impairment; FDA-approved pediatric GAD

— Buspirone = non-sedating, non-addictive, slow onset (2–4 weeks); ineffective in benzo-experienced patients sometimes

— Hydroxyzine = non-addictive, anticholinergic — avoid in elderly

— Pregabalin = European first-line; Schedule V in US

— Worry >6 months, multi-domain, with somatic symptoms → GAD

— New anxiety after 40 with weight loss → hyperthyroidism

— Paroxysmal HTN + headache + sweating → pheochromocytoma

— Discrete 10-minute attacks → panic disorder

— Fear of scrutiny → social anxiety

— Obsessions + compulsions → OCD

— Trauma + flashbacks → PTSD

— Stressor <3 months ago → adjustment disorder

— GAD criteria: "WATCHERS" — Worry, Anxiety, Tension, Concentration, Hyperarousal/Headache, Energy loss, Restlessness, Sleep

— Or DSM "3 of 6 RIMFCS" — Restlessness, Irritability, Muscle tension, Fatigue, Concentration, Sleep

— Diagnosis: ≥6 months

— SSRI response: 4–6 weeks

— Full benefit: 8–12 weeks

— Maintenance: ≥12 months after remission

— Pregnancy follow-up: peripartum visits + EPDS

Board pearl: When a Step 3 stem mentions a patient with anxiety AND fibromyalgia, neuropathic pain, or chronic low back pain, duloxetine is often the highest-value single-agent answer.

Comorbidity pearls:

Drug-specific high-yield facts:

Test-taking discriminators:

Mnemonics:

Time intervals to memorize:

Board Question Stem Patterns

— 34-year-old woman, 8 months of constant worry about work, family, finances, with insomnia, muscle tension, fatigue, irritability; normal TSH, ECG, exam. Best initial therapy? → SSRI + CBT (escitalopram or sertraline)

— 75-year-old with new anxiety, on HCTZ, requests "something for nerves." Tempting wrong answer: lorazepam. Correct: sertraline or low-dose escitalopram; avoid benzodiazepines and paroxetine (Beers list)

— 28-year-old at 12 weeks gestation with worsening GAD despite CBT. Best medication? → sertraline (not paroxetine)

— Patient on escitalopram 20 mg for 12 weeks with GAD-7 still 14. Next step? → switch to SNRI (venlafaxine or duloxetine) or augment with buspirone; not benzodiazepine

— Patient stopped venlafaxine abruptly, now has dizziness, paresthesias, "brain zaps," flu-like symptoms. Diagnosis? → SSRI/SNRI discontinuation syndrome; resume and taper slowly

— 45-year-old with new "anxiety," tremor, 12-lb weight loss, HR 108, fine tremor. Next step? → TSH (hyperthyroidism), not start sertraline

— 50-year-old with episodic palpitations, HTN to 210/120, headache, sweating. Next step? → plasma metanephrines, not benzodiazepine

— Patient with GAD-7 = 14 and PHQ-9 = 16. Best treatment? → single SSRI treats both

— Anxiety post-MI affecting recovery. Best agent? → sertraline (SADHART)

— Patient with GAD now expressing suicidal ideation with plan and access to firearm. Next step? → inpatient psychiatric admission; means restriction; do not discharge home

— Elderly woman 3 weeks after starting escitalopram, now confused with Na 126. Diagnosis? → SSRI-induced SIADH; stop SSRI, fluid restrict, consider alternative

— 14-year-old with multi-domain worry, school avoidance, somatic complaints for 8 months. First-line? → CBT, add SSRI (sertraline or escitalopram) if moderate-severe; duloxetine FDA-approved for GAD ≥7 years

Key distinction: On Step 3, the answer is rarely "benzodiazepine" — always look for the SSRI/SNRI + CBT combination or the organic mimic redirect.

Classic GAD stem:

Elderly trap stem:

Pregnancy stem:

Treatment-resistant stem:

Discontinuation syndrome stem:

Organic mimic stem:

Comorbid depression stem:

Cardiac comorbidity:

Suicide stem:

Hyponatremia stem:

Pediatric stem:

One-Line Recap

Generalized anxiety disorder is chronic, multi-domain, difficult-to-control worry lasting ≥6 months with somatic symptoms, diagnosed clinically (GAD-7), managed first-line with SSRI/SNRI plus CBT, after excluding medical mimics like hyperthyroidism, pheochromocytoma, arrhythmia, and substance use.

Board pearl: The Step 3 right answer almost always pairs an SSRI/SNRI with CBT, prioritizes non-addictive options, and uses measurement-based follow-up with the GAD-7 — never default to benzodiazepines, and never skip the medical mimic workup in atypical or late-onset presentations. Mastery of GAD on Step 3 hinges on recognizing the chronic-worry pattern, choosing the right SSRI for the right patient, and managing follow-up cadence and transitions of care safely.

Diagnosis: ≥6 months excessive worry + ≥3 of 6 symptoms (Restlessness, Irritability, Muscle tension, Fatigue, Concentration, Sleep); rule out thyroid, cardiac, substance, and other organic mimics before treating, especially in new-onset anxiety after age 40.

First-line treatment: SSRI (sertraline, escitalopram) or SNRI (venlafaxine, duloxetine) + CBT; expect response in 4–6 weeks, full benefit in 8–12 weeks; continue ≥12 months after remission; track with serial GAD-7.

Special populations: sertraline for pregnancy/lactation and post-MI; escitalopram max 10 mg in elderly/hepatic impairment; avoid paroxetine in pregnancy and elderly; avoid benzodiazepines in elderly, substance-use history, OSA, and as monotherapy.

Safety musts: screen suicidality (C-SSRS, 988), counsel on black-box warning <25, monitor sodium at 2–4 weeks in elderly, monitor BP with venlafaxine, taper SSRIs gradually to prevent discontinuation syndrome, and document informed consent including pregnancy and driving precautions.