Generalised Anxiety Disorder

Generalised Anxiety Disorder (GAD) is a chronic, "free-floating" anxiety disorder defined by excessive, uncontrollable worry about multiple everyday matters, persisting for at least 6 months and accompanied by somatic and cognitive symptoms. It is one of the most under-diagnosed yet eminently treatable psychiatric conditions and a recurrent NEET PG favourite for its differentiation from normal worry and from panic disorder.

Definition & Diagnostic Criteria

GAD is characterised by persistent and excessive anxiety and worry (apprehensive expectation) that the patient finds difficult to control, occurring more days than not for ≥6 months, focused on a number of events or activities (work, health, finances, family) rather than a single circumscribed concern.

The worry must be associated with somatic/cognitive symptoms and cause clinically significant distress or functional impairment, and must not be better explained by another disorder or a substance/medical condition.

High-yield: The single most-tested anchor is the 6-month duration of excessive, difficult-to-control worry. A "diffuse, free-floating, non-episodic" anxiety = GAD. "Episodic, paroxysmal, peaks in 10 minutes" = panic disorder.

DSM-5 vs ICD-11 — symptom requirements

Feature	DSM-5	ICD-11
Core feature	Excessive worry, hard to control	Marked apprehension / "general worry" or worry about multiple events
Duration	≥6 months	Several months (≥several)
Associated symptoms needed	≥3 of 6 (only 1 in children)	Autonomic + muscle tension + restlessness
The 6 DSM symptoms	Restlessness, easy Fatigue, poor Concentration, Irritability, Muscle tension, Sleep disturbance	—
Exclusion	Not due to substance/medical/other mental disorder	Same

Mnemonic for the DSM-5 associated symptoms — "WATCHERS" is popular, but the cleaner fit is "Worry FRICMS": Fatigue, Restlessness, Irritability, Concentration impaired, Muscle tension, Sleep disturbance. Need ≥3 of these 6 in adults.

High-yield: Muscle tension is the symptom that most reliably distinguishes GAD from major depressive disorder and from other anxiety disorders — it is the most specific somatic marker.

Epidemiology

• Lifetime prevalence ~5–6%; 12-month prevalence ~3%.
• Female:male ≈ 2:1 (like most anxiety/mood disorders).
• Bimodal-leaning onset; mean onset around 30 years, often later than other anxiety disorders, and frequently insidious. Can present for the first time in the elderly.
• Highly comorbid: >50–90% have another disorder — most commonly major depression, panic disorder, social anxiety, and substance use. "Pure" GAD is the exception, not the rule.

Etiology & Pathophysiology

Neurotransmitter dysregulation underlies the disorder:

• GABA — reduced inhibitory tone; benzodiazepines and the GABA-modulating effect explain rapid anxiolysis.
• Serotonin (5-HT) — dysregulation; basis for SSRI/SNRI efficacy.
• Noradrenaline — locus coeruleus hyperactivity drives autonomic symptoms (palpitations, sweating, tremor).
• Glutamate — excitatory excess.

Neurocircuitry: an over-reactive amygdala with deficient top-down regulation by the prefrontal cortex, plus involvement of the bed nucleus of the stria terminalis (sustained, non-cued anxiety) — contrasting with the phasic, cued fear circuit of panic disorder.

Genetics: heritability ~30%; shares genetic loading with major depression (the two are considered partly the same diathesis expressed differently). Temperament of behavioural inhibition and the trait neuroticism are predisposing.

High-yield: GAD and major depressive disorder share a common genetic substrate; environment largely determines which phenotype emerges.

Clinical Features

The presentation straddles psychological and somatic domains, and patients frequently present first to physicians, not psychiatrists.

• Psychological: chronic apprehension, "what-if" catastrophising, feeling on edge, irritability, poor concentration, indecisiveness, anticipatory dread.
• Motor tension: muscle aches, tension headaches, trembling, inability to relax, fatigability.
• Autonomic hyperactivity: palpitations, sweating, dry mouth, epigastric discomfort, urinary frequency, dizziness.
• Sleep: classically initial insomnia (difficulty falling asleep due to worry), unrefreshing sleep.

Because somatic complaints dominate, GAD is a classic cause of medically unexplained symptoms and repeated, negative work-ups for cardiac or GI disease.

High-yield: A patient with chronic headaches, IBS-like symptoms, fatigue, and "always worrying about everything" with normal investigations — think GAD.

Screening & Assessment — GAD-7

The GAD-7 is the standard validated self-report screening and severity tool — 7 items, each scored 0–3 over the last 2 weeks, total range 0–21.

GAD-7 Score	Severity
0–4	Minimal anxiety
5–9	Mild
10–14	Moderate
15–21	Severe

High-yield: A GAD-7 cut-off of ≥10 is the commonly cited threshold for "probable GAD" warranting further assessment/treatment (sensitivity ~89%, specificity ~82%). The first two items (GAD-2) form a brief screen.

Diagnosis & Investigation of Choice

GAD is a clinical diagnosis; there is no confirmatory laboratory test. The "investigation of choice" question is really about ruling out mimics:

• TSH / free T4 — exclude hyperthyroidism (the classic organic mimic; weight loss, heat intolerance, tremor, tachycardia).
• ECG ± cardiac work-up if palpitations/chest pain prominent.
• Glucose (hypoglycaemia), calcium.
• Consider phaeochromocytoma (episodic; but more panic-like), carcinoid, caffeine/stimulant/withdrawal states.

Stepwise diagnostic approach: Excessive worry ≥6 months → rule out medical mimic (TSH first) → rule out substance/withdrawal (caffeine, alcohol, stimulants) → exclude another primary psychiatric disorder → confirm ≥3 somatic symptoms + impairment → diagnose GAD + grade with GAD-7.

High-yield: The first screening investigation before labelling anxiety as primary GAD is thyroid function (TSH) — hyperthyroidism is the most commonly tested organic mimic.

Management

Treatment combines psychotherapy and pharmacotherapy; for mild cases, psychotherapy alone may suffice.

First-line: Psychotherapy

Cognitive Behavioural Therapy (CBT) is the psychotherapy of choice — equal in efficacy to medication and with more durable benefit. Techniques: cognitive restructuring of catastrophic thoughts, worry exposure, relaxation training, and applied relaxation.

First-line: Pharmacotherapy

SSRIs and SNRIs are the first-line drugs of choice.

• SSRIs: escitalopram, sertraline, paroxetine.
• SNRIs: venlafaxine (XR), duloxetine.
• Start low, go slow; anxiety may transiently worsen in the first 1–2 weeks ("jitteriness/activation"), so warn the patient.
• Therapeutic effect takes 2–4 weeks (often 4–6); treat for ≥12 months after response to prevent relapse.

Drug class	Examples	Role	Key caution
SSRI	Escitalopram, sertraline, paroxetine	First-line	Initial activation, sexual dysfunction, discontinuation syndrome (paroxetine)
SNRI	Venlafaxine XR, duloxetine	First-line	Dose-related hypertension (venlafaxine), monitor BP
Azapirone	Buspirone	Second-line / augmentation	Delayed onset (1–2 wks), no dependence, not for acute relief
Benzodiazepine	Diazepam, clonazepam, lorazepam, alprazolam	Short-term only	Dependence, sedation, falls in elderly
Anticonvulsant	Pregabalin	Effective alternative (esp. Europe)	Sedation, abuse potential
Antihistamine	Hydroxyzine	Non-dependence option	Sedation, anticholinergic

Buspirone — the classic exam drug

A 5-HT1A partial agonist azapirone. Non-sedating, no dependence, no withdrawal, no abuse potential, and no interaction with alcohol — but takes 1–2 weeks to act, so it is useless for acute anxiety relief. Especially useful in patients with substance-use history where benzodiazepines are best avoided.

High-yield: Buspirone = 5-HT1A partial agonist; slow onset; no dependence; ineffective for acute/PRN use. It does NOT relieve benzodiazepine withdrawal and does not work for panic disorder.

Role of benzodiazepines

Benzodiazepines act rapidly and are useful only for short-term relief (≤2–4 weeks) while waiting for the SSRI/SNRI to take effect, or for acute crises. They are not first-line for chronic GAD because of tolerance, dependence, cognitive impairment, and falls (especially in the elderly).

High-yield: Benzodiazepines provide bridging therapy for the 2–4 week SSRI latency; they are not maintenance treatment. Avoid in elderly, in COPD/sleep apnoea, and in those with substance misuse.

Stepwise pharmacological flow: SSRI or SNRI (± short benzodiazepine bridge) → if no response in 6–8 weeks, switch to another SSRI/SNRI → then consider pregabalin or buspirone → augment / specialist referral / combine with CBT for resistant cases.

Complications

• Major depressive disorder — the commonest complication; worsens prognosis.
• Substance use disorders — alcohol and benzodiazepine dependence (self-medication).
• Increased suicide risk when comorbid with depression.
• Chronic medical morbidity: hypertension, peptic/GI symptoms, IBS, coronary disease association.
• Significant functional and occupational impairment; high healthcare utilisation.

Key Differentials

Condition	Distinguishing feature
Normal worry	Proportionate, controllable, not pervasive, no impairment, no somatic cluster, < persistent 6 months
Panic disorder	Episodic, abrupt panic attacks peaking in ~10 min + anticipatory fear of attacks; GAD is sustained/non-episodic
Major depression	Pervasive low mood/anhedonia primary; if both meet criteria, diagnose both. Anxiety often secondary
Social anxiety disorder	Worry confined to social/performance scrutiny
OCD	Worry takes form of intrusive obsessions + compulsions
PTSD	Anxiety tied to re-experiencing a traumatic event
Hyperthyroidism	Weight loss, heat intolerance, tachycardia, raised free T4, low TSH
Substance/caffeine intoxication or withdrawal	Temporal link to substance; resolves on cessation
Adjustment disorder with anxiety	Identifiable stressor, <6 months, resolves
Illness anxiety / somatic symptom disorder	Worry focused specifically on having a disease

High-yield: GAD vs Panic disorder is the single most common exam pairing — diffuse, continuous, free-floating worry = GAD; paroxysmal, crescendo attacks with fear of dying = panic disorder.

Prognosis

Chronic and fluctuating, often waxing and waning with life stress. Only about a third achieve full remission; the disorder is frequently lifelong but very responsive to combined CBT + SSRI/SNRI. Comorbid depression and personality pathology worsen outcome.

Recently asked / exam angle

• Duration criterion: "Excessive worry for at least how many months defines GAD?" → 6 months.
• Drug of choice: First-line for GAD → SSRI/SNRI (not benzodiazepine, not buspirone alone).
• Buspirone MOA: 5-HT1A partial agonist — recurring single-best-answer.
• GAD-7: identify it as the screening/severity scale; cut-off ≥10.
• Benzodiazepine role: "short-term/bridging only" — distractor options call them first-line; reject that.
• Most specific somatic symptom: muscle tension.
• Organic mimic to exclude first: hyperthyroidism (TSH).
• GAD vs panic disorder clinical vignette differentiation.
• "Non-dependence-producing anxiolytic suitable for a patient with alcohol use" → buspirone (or hydroxyzine/pregabalin distractors).
• Pregabalin recognised as an effective alternative anxiolytic — increasingly appearing.

Rapid revision

1. GAD = excessive, uncontrollable, free-floating worry ≥6 months about multiple domains, with impairment.
2. DSM-5 needs ≥3 of 6 somatic symptoms (FRICMS: Fatigue, Restlessness, Irritability, Concentration impaired, Muscle tension, Sleep disturbance); only 1 needed in children.
3. Muscle tension is the most specific symptom; initial insomnia is the classic sleep complaint.
4. F:M = 2:1; later mean onset (~30 yrs) than other anxiety disorders; highly comorbid with depression.
5. Pathophysiology: GABA↓, serotonin/noradrenaline dysregulation, hyperactive amygdala, weak prefrontal control.
6. GAD-7 = screening + severity scale; ≥10 = probable GAD; scored over last 2 weeks, range 0–21.
7. Always check TSH to exclude hyperthyroidism before labelling primary anxiety.
8. First-line drugs: SSRIs/SNRIs; first-line psychotherapy: CBT; effect in 2–4 weeks; treat ≥12 months.
9. Buspirone = 5-HT1A partial agonist — non-sedating, no dependence, slow onset, useless for acute relief and for panic disorder.
10. Benzodiazepines = short-term bridge only (≤2–4 weeks); avoid in elderly, COPD, substance misuse.
11. Pregabalin and hydroxyzine are useful non-SSRI alternatives.
12. Differentiate GAD (continuous worry) from panic disorder (episodic crescendo attacks) — top exam pairing.