Anxiety Disorders in Adults: Comprehensive Clinical Management

SECTION 1: Clinical Overview

1.1 Summary

Anxiety disorders represent the most prevalent class of mental disorders worldwide, characterized by excessive fear, anxiety, and associated behavioral disturbances that cause clinically significant distress or functional impairment. [1] According to the Global Burden of Disease Study 2019, anxiety disorders affect approximately 301 million individuals globally, making them one of the leading causes of disability-adjusted life years (DALYs) in the mental health domain. [2] The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) classifies anxiety disorders as a distinct nosological category comprising generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), specific phobias, and agoraphobia, each with unique diagnostic criteria but sharing core features of excessive and persistent fear and anxiety. [3]

The clinical significance of anxiety disorders extends far beyond subjective distress. These conditions are associated with substantial functional impairment, healthcare utilization, reduced work productivity, and diminished quality of life. [4] The lifetime prevalence of any anxiety disorder ranges from 15% to 33.7% in high-income countries, with 12-month prevalence estimates of approximately 18.1% in the United States adult population. [5] Anxiety disorders demonstrate high comorbidity with major depressive disorder (MDD), with approximately 60% of individuals with anxiety disorders experiencing a comorbid mood disorder during their lifetime. [6] This comorbidity is associated with greater severity, poorer treatment response, and higher suicide risk.

Contemporary management follows an evidence-based stepped-care approach integrating psychological therapies—predominantly cognitive behavioral therapy (CBT)—with pharmacological interventions including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and adjunctive agents. [7] The National Institute for Health and Care Excellence (NICE) guidelines recommend low-intensity psychological interventions for mild anxiety, progressing to high-intensity CBT and/or pharmacotherapy for moderate-to-severe presentations. [8] Prognosis is generally favorable with evidence-based interventions, though chronic trajectories are common without treatment, emphasizing the importance of early identification and intervention.

1.2 Key Facts

• Definition: Anxiety disorders are characterized by excessive fear (emotional response to perceived or real imminent threat) and anxiety (anticipation of future threat) that are out of proportion to actual risk and persist beyond developmentally appropriate periods. [3]
• Global Prevalence: Approximately 4.05% (301 million individuals) globally; 7.3% in high-income countries, representing the most common mental disorder category. [2]
• Lifetime Prevalence: 33.7% for any anxiety disorder in the United States adult population, with women having approximately 2-fold higher rates than men. [5]
• 12-Month Prevalence: 18.1% in US adults; GAD affects 3.1%, panic disorder 2.7%, social anxiety disorder 7.1%, specific phobias 8.7%, and agoraphobia 0.8%. [5]
• Age of Onset: Median age of onset is 11 years for specific phobias, 13 years for social anxiety disorder, 20 years for panic disorder, and 31 years for generalized anxiety disorder. [9]
• Sex Distribution: Female-to-male ratio approximately 2:1 across most anxiety subtypes; this difference emerges at puberty and persists throughout the lifespan. [10]
• Mortality Risk: Indirectly increased via suicide (10-fold higher risk in severe cases), cardiovascular disease association (26-48% increased risk), and substance use disorders. [11]
• Disability Burden: Anxiety disorders rank as the sixth leading cause of disability globally (measured in years lived with disability). [2]
• Comorbidity: 60% lifetime comorbidity with major depression; 30% comorbidity with substance use disorders. [6]
• Gold Standard Assessment: Structured Clinical Interview for DSM-5 (SCID-5) or validated screening tools including GAD-7 (sensitivity 89%, specificity 82% at cutoff ≥10). [12]
• First-line Treatment: Cognitive behavioral therapy (CBT) and SSRIs (sertraline, escitalopram, paroxetine) demonstrate Level I evidence. [7]
• Treatment Response: Approximately 50-60% of patients achieve remission with first-line treatment; combined CBT plus pharmacotherapy demonstrates superior outcomes. [13]

1.3 Clinical Pearls

Diagnostic Pearl: "The Somatic Presentation" Approximately 40% of patients with anxiety disorders present primarily with physical symptoms to primary care settings—palpitations, dyspnea, gastrointestinal disturbance, or chronic pain—rather than reporting psychological distress. [14] Always screen for anxiety disorders in patients with medically unexplained symptoms, irritable bowel syndrome, chronic fatigue, or frequent emergency department presentations for chest pain with negative cardiac workup.

Examination Pearl: "The Panic-Cardiac Mimicry" Panic attacks closely mimic acute coronary syndrome and pulmonary embolism, with chest pain, dyspnea, and autonomic symptoms. Before diagnosing panic disorder, complete cardiac and pulmonary evaluation is mandatory. However, remember that panic disorder and coronary artery disease can coexist—treat both conditions when present. [15]

Treatment Pearl: "Start Low, Go Slow" When initiating SSRIs for anxiety disorders, begin at half the standard antidepressant dose (e.g., sertraline 25mg, escitalopram 5mg). Anxiety patients exhibit heightened sensitivity to the initial activating effects of serotonergic agents—transient increases in jitteriness, insomnia, and anxiety during the first 7-14 days frequently lead to premature discontinuation. [7] Warn patients about this paradoxical worsening and provide reassurance that it typically resolves within 2 weeks.

Pitfall Warning: "The Benzodiazepine Trap" Avoid prescribing benzodiazepines as monotherapy or for long-term use in anxiety disorders. While providing immediate symptomatic relief, benzodiazepines interfere with extinction learning essential for CBT efficacy and carry substantial risks of physiological dependence, cognitive impairment, and increased fall risk. [16] NICE guidelines recommend benzodiazepines only for short-term crisis management (maximum 2-4 weeks).

Mnemonic: "WATCHERS" for GAD Diagnostic Criteria Worry excessive (most days for ≥6 months), Anxiety difficult to control, Tension in muscles, Concentration difficulty, Hyperarousal (irritability), Energy loss (fatigue easily), Restlessness, Sleep disturbance. DSM-5 requires ≥3 of the 6 associated symptoms (excluding worry) for adults. [3]

Emergency Pearl: "Agitation Equals Risk" Psychomotor agitation in the context of anxiety—pacing, inability to sit still, wringing hands—represents a high-risk state for impulsive suicidal behavior. This agitated anxiety state warrants immediate escalation of care, one-to-one observation, and formal suicide risk assessment. [17] Never dismiss severe agitation as "just anxiety."

Exam Pearl: "Social Anxiety vs. Agoraphobia" Examiners frequently test this distinction: Social anxiety disorder involves fear of scrutiny and negative evaluation by others in social or performance situations. Agoraphobia involves fear of situations where escape may be difficult or help unavailable during panic-like symptoms—public transport, open spaces, enclosed spaces, crowds, or being outside home alone. [3] The cognitive focus differs: embarrassment vs. entrapment.

Evidence Pearl: "CBT Durability" Meta-analytic evidence demonstrates that the treatment gains from CBT for anxiety disorders are maintained at 12-24 month follow-up and may confer protection against relapse superior to pharmacotherapy alone. [18] This durability reflects the acquisition of active coping skills and corrective learning that persist after treatment termination.

1.4 Why This Matters Clinically

Patient Outcomes: Untreated anxiety disorders follow chronic trajectories with progressive functional decline. Longitudinal studies demonstrate that early-onset anxiety predicts subsequent development of major depression, substance use disorders, and cardiovascular disease. [11] The chronic hypercortisolemic state associated with untreated anxiety contributes to endothelial dysfunction, accelerated atherosclerosis, and increased risk of myocardial infarction and stroke—with hazard ratios of 1.26-1.48 for cardiovascular events. [19] Early treatment can interrupt this pathophysiological cascade.

Healthcare Burden: Anxiety disorders generate enormous healthcare costs—estimated at $42-47 billion annually in the United States—with over half attributed to non-psychiatric medical utilization as patients seek evaluation for somatic symptoms. [4] Patients with undiagnosed anxiety disorders are high utilizers of emergency departments, specialist consultations, and diagnostic testing, creating significant inefficiency in healthcare delivery.

Quality of Life: Anxiety disorders substantially impair quality of life across social, occupational, and physical domains. Social anxiety disorder leads to educational underachievement, occupational underperformance, and impaired intimate relationships. Agoraphobia can cause complete housebound status. Panic disorder generates anticipatory anxiety that restricts daily activities. [4]

Medico-legal Considerations: Failure to screen for suicidality in anxiety disorder presentations is a recognized source of litigation. Clinicians must document formal risk assessment, safety planning, and appropriate referral pathways. Additionally, prescribing benzodiazepines without discussing addiction risk or for prolonged periods creates liability exposure.

Training Relevance: Anxiety disorders are the most common psychiatric presentations in primary care and emergency medicine settings. Mastery of evidence-based assessment and management is a core competency for all medical practitioners, not exclusively psychiatrists. Examinations (MRCPsych, MRCP, USMLE) consistently test anxiety disorder knowledge.

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SECTION 2: Classification and DSM-5-TR Diagnostic Criteria

2.1 Overview of Anxiety Disorder Spectrum

The DSM-5-TR classifies anxiety disorders as a distinct category characterized by features of excessive fear and anxiety with related behavioral disturbances. [3] The disorders differ primarily in the types of objects or situations that induce fear, anxiety, or avoidance behavior, and the associated cognitive ideation.

2.2 Generalized Anxiety Disorder (GAD)

DSM-5-TR Diagnostic Criteria: [3]

A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (work, school performance, health).

B. Difficulty controlling the worry.

C. Associated with three or more of the following six symptoms (only one required in children):

1. Restlessness or feeling keyed up or on edge
2. Being easily fatigued
3. Difficulty concentrating or mind going blank
4. Irritability
5. Muscle tension
6. Sleep disturbance (difficulty falling/staying asleep, restless unsatisfying sleep)

D. Causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

E. Not attributable to the physiological effects of a substance or another medical condition.

F. Not better explained by another mental disorder.

Prevalence and Course: Lifetime prevalence is 5.7-6.2% with 12-month prevalence of 2.9-3.1%. [5] GAD demonstrates the latest median age of onset (31 years) among anxiety disorders and follows a chronic waxing-and-waning course. Full remission rates are low without treatment (approximately 20% at 2 years).

2.3 Panic Disorder

DSM-5-TR Diagnostic Criteria: [3]

A. Recurrent unexpected panic attacks—an abrupt surge of intense fear or discomfort reaching peak within minutes, with four or more of 13 symptoms:

• Palpitations, pounding heart, or accelerated heart rate
• Sweating
• Trembling or shaking
• Sensations of shortness of breath or smothering
• Feelings of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Dizziness, unsteadiness, light-headedness, or faintness
• Chills or heat sensations
• Paresthesias (numbness or tingling)
• Derealization or depersonalization
• Fear of losing control or "going crazy"
• Fear of dying

B. At least one attack followed by ≥1 month of:

• Persistent concern about additional attacks or their consequences
• Significant maladaptive behavioral change related to attacks (avoidance)

C-D. Not attributable to substances, medical conditions, or other mental disorders.

Prevalence and Course: Lifetime prevalence 4.7% with 12-month prevalence 2.7%. [5] Peak onset in late adolescence to mid-30s. Panic attacks are necessary but not sufficient for panic disorder—approximately 23% of the general population experience isolated panic attacks without developing the disorder.

2.4 Agoraphobia

DSM-5-TR Diagnostic Criteria: [3]

A. Marked fear or anxiety about two or more of five situations:

1. Using public transportation
2. Being in open spaces
3. Being in enclosed spaces
4. Standing in line or being in a crowd
5. Being outside of the home alone

B. Fear relates to thoughts that escape might be difficult or help unavailable in the event of panic-like symptoms.

C. Agoraphobic situations almost always provoke fear or anxiety.

D. Situations actively avoided, require companion, or endured with intense fear.

E. Fear is out of proportion to actual danger.

F. Fear persists for ≥6 months.

G-H. Causes significant distress/impairment; not better explained by other conditions.

Key Change in DSM-5: Agoraphobia is now a separate diagnosis from panic disorder. Approximately one-third of individuals with agoraphobia have never experienced panic symptoms. [3]

2.5 Social Anxiety Disorder (Social Phobia)

DSM-5-TR Diagnostic Criteria: [3]

A. Marked fear or anxiety about one or more social situations with possible scrutiny by others (social interactions, being observed, performing in front of others).

B. Fear of negative evaluation—acting in a way that will be embarrassing, humiliating, or lead to rejection.

C. Social situations almost always provoke fear or anxiety.

D. Social situations avoided or endured with intense fear/anxiety.

E. Fear is out of proportion to actual threat.

F. Persists for ≥6 months.

G-H. Causes significant distress/impairment; not attributable to substances or other conditions.

Specifier: Performance only—if fear restricted to speaking or performing in public.

Prevalence and Course: Lifetime prevalence 12.1% with 12-month prevalence 7.1%. [5] Typically begins in mid-teens with high chronicity. Early onset predicts greater severity and comorbidity.

2.6 Specific Phobia

DSM-5-TR Diagnostic Criteria: [3]

A. Marked fear or anxiety about a specific object or situation (e.g., flying, heights, animals, injections, blood).

B. Phobic object or situation almost always provokes immediate fear/anxiety.

C. Object or situation actively avoided or endured with intense fear/anxiety.

D. Fear is out of proportion to actual danger.

E. Persists for ≥6 months.

F-G. Causes significant distress/impairment; not better explained by other conditions.

Specifiers (by type):

• Animal (spiders, insects, dogs)
• Natural environment (heights, storms, water)
• Blood-injection-injury (needles, invasive medical procedures)
• Situational (airplanes, elevators, enclosed spaces)
• Other (choking, vomiting, loud sounds)

Prevalence and Course: Lifetime prevalence 12.5% with 12-month prevalence 8.7%—the most common anxiety disorder. [5] Median onset in childhood (7-11 years). Blood-injection-injury phobia is unique in producing vasovagal syncope rather than sympathetic activation.

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SECTION 3: Epidemiology

3.1 Prevalence and Incidence

Temporal Trends: Anxiety disorder prevalence increased by approximately 26% globally during the COVID-19 pandemic (2020), with particular impacts on young adults and women. [2] Pre-pandemic trends showed gradual increases in high-income countries, attributed to changing social structures, digital connectivity, and economic uncertainty.

3.2 Demographics Table

3.3 Risk Factors

Non-Modifiable Risk Factors:

Modifiable Risk Factors:

3.4 Protective Factors

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SECTION 4: Pathophysiology

4.1 Neurobiological Model of Anxiety

Anxiety disorders arise from dysregulation within interconnected neural circuits mediating threat detection, emotional processing, and fear extinction. The contemporary understanding integrates genetic vulnerability, environmental modifiers, and neuroplastic changes that create a self-perpetuating cycle of hypervigilance and maladaptive avoidance.

4.2 Neural Circuitry: The Fear Network

Core Structures:

Circuit Dysfunction: In anxiety disorders, the prefrontal cortex fails to provide adequate inhibitory control over amygdala activity. This results in "emotional hijacking"—threat-related stimuli trigger disproportionate fear responses without effective top-down modulation. [20] The hippocampus, which normally contextualizes threats and signals safety, shows reduced volume and impaired function in chronic anxiety, compromising the brain's ability to distinguish between genuinely dangerous and safe situations.

4.3 Neurotransmitter Systems

GABAergic System: Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. Anxiety disorders are associated with reduced GABAergic tone, particularly decreased sensitivity or density of GABA-A receptors (alpha-2 and alpha-3 subunits) in limbic structures. [21] This reduction diminishes inhibitory control over excitatory circuits. Benzodiazepines exert their anxiolytic effect by enhancing GABA-A receptor function.

Serotonergic System: Serotonin (5-HT) modulates emotional responses through extensive projections from the raphe nuclei to limbic and prefrontal regions. The 5-HT1A receptor subtype is particularly implicated in anxiety—reduced 5-HT1A binding in the amygdala and raphe nuclei correlates with anxiety severity. [21] The 5-HTTLPR polymorphism affecting serotonin transporter expression influences stress reactivity and anxiety vulnerability. SSRIs enhance serotonergic transmission and are first-line pharmacotherapy.

Noradrenergic System: The locus coeruleus noradrenergic system drives the physiological arousal component of anxiety—tachycardia, tremor, sweating, and hypervigilance. Hyperactivity of this system underlies the somatic manifestations of panic attacks and generalized anxiety. [22] Beta-blockers (propranolol) target peripheral noradrenergic effects for performance anxiety.

HPA Axis Dysregulation: The hypothalamic-pituitary-adrenal (HPA) axis demonstrates altered function in anxiety disorders. Corticotropin-releasing hormone (CRH) hyperactivity in the hypothalamus drives sustained cortisol elevation. [20] While acute cortisol enhances survival responses, chronic hypercortisolemia is neurotoxic—particularly to hippocampal neurons—creating a feedback loop that perpetuates anxiety vulnerability.

Glutamatergic System: Glutamate, the primary excitatory neurotransmitter, contributes to anxiety through NMDA receptor-mediated hyperexcitability. Excessive glutamatergic activity in the amygdala contributes to fear conditioning and "kindling"—whereby repeated anxiety episodes progressively lower the threshold for future episodes. [21]

4.4 Genetics and Epigenetics

Heritability: Twin studies demonstrate 30-50% heritability for anxiety disorders, indicating substantial genetic contribution with significant environmental influence. [23]

Candidate Genes:

Epigenetic Modifications: Early life adversity induces DNA methylation changes, particularly in the NR3C1 gene (glucocorticoid receptor), permanently altering HPA axis set-point and stress reactivity. [23] These epigenetic marks can be partially reversed through environmental enrichment and psychotherapeutic intervention.

4.5 The Fear Conditioning Model

Anxiety disorders involve aberrant fear conditioning and failed extinction learning:

1. Acquisition: Neutral stimuli become associated with threat through classical conditioning (e.g., panic attack in supermarket → supermarket becomes conditioned stimulus)

2. Generalization: Fear spreads from original trigger to similar stimuli (supermarket → all stores → leaving home)

3. Avoidance: Behavioral escape from feared stimuli provides immediate relief (negative reinforcement) but prevents extinction learning

4. Failed Extinction: Unlike healthy individuals, those with anxiety disorders fail to extinguish conditioned fear responses. The vmPFC fails to signal safety, and hippocampal context-dependent memory is impaired

Therapeutic Implications: CBT with exposure therapy directly targets this circuit by repeatedly exposing patients to feared stimuli without negative outcome, promoting extinction learning and strengthening prefrontal inhibitory control over the amygdala. [18]

4.6 Interoceptive Sensitivity Model (Panic Disorder)

Panic disorder involves heightened interoceptive sensitivity—excessive attention to and catastrophic misinterpretation of normal bodily sensations. [15] Minor physiological fluctuations (heart rate variation, breathing irregularity) are detected, interpreted as dangerous, triggering further autonomic activation in a positive feedback loop culminating in full panic attack. The insula cortex, which processes visceral sensation, shows heightened reactivity in panic disorder.

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SECTION 5: Clinical Presentation

5.1 Symptoms by Anxiety Disorder Subtype

Generalized Anxiety Disorder:

Panic Disorder:

Anticipatory Anxiety: Between attacks, persistent worry about future attacks and their consequences (embarrassment, medical emergency, loss of control).

Agoraphobic Avoidance: Many patients develop avoidance of situations associated with panic attacks, which may progress to complete agoraphobia.

Social Anxiety Disorder:

Specific Phobia:

Immediate, intense fear upon exposure to the specific phobic stimulus. Unlike other anxiety disorders, anxiety is circumscribed to the phobic object/situation. Blood-injection-injury phobia uniquely produces vasovagal syncope (biphasic response: initial tachycardia followed by bradycardia and hypotension).

5.2 Signs on Examination

General Observation:

• Appearance: Tense posture, furrowed brow, hypervigilance
• Behavior: Restlessness, fidgeting, frequent position shifts, poor eye contact (SAD)
• Speech: Rapid or hesitant, circumstantial when anxious

Vital Signs (during acute anxiety/panic):

• Tachycardia (HR 100-150 bpm)
• Tachypnea (RR 20-30/min)
• Mildly elevated blood pressure
• Normal oxygen saturation (distinguishes from medical emergency)

Physical Signs:

Mental Status Examination:

• Mood: "Anxious," "on edge," "terrified"
• Affect: Anxious, apprehensive, constricted to anxious range; congruent with mood
• Thought process: Goal-directed but may be circumstantial; racing thoughts
• Thought content: Worry, catastrophizing; check for suicidal ideation
• Perception: Usually normal; may report depersonalization/derealization during panic
• Cognition: May show impaired concentration; otherwise intact
• Insight: Usually preserved—patients recognize worry is excessive
• Judgment: May be impaired by avoidance behaviors

5.3 Red Flags

[!CAUTION] RED FLAGS — Require Immediate Action:

• Suicidal Ideation/Intent: Express desire to die or "escape" the anxiety permanently; assess plan, means, intent
• Psychomotor Agitation: Severe restlessness, pacing, inability to sit still—high risk for impulsive self-harm
• Chest Pain with Risk Factors: New-onset, especially with cardiac risk factors—exclude ACS before attributing to panic
• Syncope: Loss of consciousness is unusual in panic (except blood-injury phobia)—evaluate for cardiac arrhythmia
• Focal Neurological Signs: New weakness, speech changes—consider stroke or neurological emergency
• First Panic Attack After Age 45: Higher likelihood of medical etiology (cardiac, pulmonary, endocrine)
• Acute Benzodiazepine Withdrawal: Seizure risk; requires medical management
• Severe Weight Loss: Indicates severe anxiety-related anorexia or occult medical condition

5.4 Screening and Assessment Tools

GAD-7 Interpretation: [12]

• 0-4: Minimal anxiety
• 5-9: Mild anxiety
• 10-14: Moderate anxiety
• 15-21: Severe anxiety

Sensitivity 89%, specificity 82% at cutoff ≥10 for GAD diagnosis.

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SECTION 6: Differential Diagnosis

6.1 Psychiatric Differential Diagnosis

6.2 Medical Differential Diagnosis

Critical Rule: Always exclude medical causes of anxiety before establishing a primary anxiety disorder diagnosis, particularly in new-onset anxiety, atypical presentations, treatment-resistant cases, or anxiety with onset after age 45.

6.3 Investigations to Exclude Medical Causes

First-Line (All Patients):

• Full blood count (anemia, infection)
• Thyroid function tests (TSH, Free T4)
• Blood glucose
• Basic metabolic panel (electrolytes, calcium)
• ECG (arrhythmia)

Second-Line (Based on Clinical Suspicion):

• Liver function tests (hepatic encephalopathy, alcohol)
• Urine drug screen (substance-induced)
• Vitamin B12, folate, vitamin D
• Cortisol (if Cushing's suspected)
• Plasma/urine metanephrines (if pheochromocytoma suspected)
• Chest X-ray (pulmonary pathology)
• Echocardiogram (if murmur or cardiac symptoms)
• EEG (if seizure suspected)
• Brain MRI (if focal neurological signs)

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SECTION 7: Investigations

7.1 Bedside Investigations

7.2 Laboratory Investigations

7.3 Specialized Investigations (Selected Cases)

7.4 Psychological Assessment

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SECTION 8: Management

8.1 Management Algorithm

┌─────────────────────────────────────────────────────────────────────────┐
│              ANXIETY DISORDER MANAGEMENT ALGORITHM                       │
│                    (NICE Stepped Care Model)                            │
└─────────────────────────────────────────────────────────────────────────┘
                                    │
                                    ▼
              ┌─────────────────────────────────────────┐
              │        INITIAL ASSESSMENT               │
              │  • Screen with GAD-7, PHQ-9             │
              │  • Exclude medical causes (TSH, ECG)    │
              │  • Assess suicide risk                  │
              │  • Identify disorder subtype            │
              │  • Evaluate severity and impairment     │
              └─────────────────────────────────────────┘
                                    │
                                    ▼
              ┌─────────────────────────────────────────┐
              │        SEVERITY STRATIFICATION          │
              │  • Mild: GAD-7 5-9, minimal impairment  │
              │  • Moderate: GAD-7 10-14                │
              │  • Severe: GAD-7 ≥15, significant       │
              │    impairment or suicidality            │
              └─────────────────────────────────────────┘
                                    │
        ┌───────────────────────────┼───────────────────────────┐
        ▼                           ▼                           ▼
┌───────────────┐         ┌───────────────┐           ┌───────────────┐
│   STEP 1-2    │         │    STEP 3     │           │    STEP 4     │
│    MILD       │         │   MODERATE    │           │    SEVERE     │
│               │         │               │           │               │
│ Psychoeducation│        │ High-intensity│           │ Specialist    │
│ Self-help     │         │ CBT (12-15    │           │ referral      │
│ (guided or    │         │ sessions)     │           │               │
│ unguided)     │         │     AND/OR    │           │ Combined CBT  │
│ Lifestyle     │         │ SSRI/SNRI     │           │ + Pharmacol.  │
│ modifications │         │               │           │               │
│ Active        │         │ Applied       │           │ Consider      │
│ monitoring    │         │ relaxation    │           │ augmentation  │
└───────────────┘         │ for GAD       │           │ strategies    │
        │                 └───────────────┘           │               │
        │                         │                   │ Crisis team   │
        │                         │                   │ if needed     │
        ▼                         ▼                   └───────────────┘
┌───────────────┐         ┌───────────────┐                   │
│ 4-6 WEEK      │         │ 8-12 WEEK     │                   ▼
│ REVIEW        │         │ REVIEW        │           ┌───────────────┐
│               │         │               │           │ TREATMENT-    │
│ If improved:  │         │ Response?     │           │ RESISTANT     │
│ Continue      │         │ (≥50% ↓ GAD-7)│           │               │
│               │         └───────┬───────┘           │ • Combine Rx  │
│ If no change: │             Yes │ No                │ • Switch      │
│ → Step up     │                 ▼                   │   medication  │
└───────────────┘         ┌───────────────┐           │ • Augment     │
                          │ CONTINUE      │           │   (pregabalin,│
                          │ 6-12 months   │           │   buspirone,  │
                          │               │           │   quetiapine) │
                          │ Then gradual  │           │ • Intensive   │
                          │ taper with    │           │   CBT program │
                          │ relapse plan  │           └───────────────┘
                          └───────────────┘

8.2 Acute/Emergency Management

For Acute Panic Attack (Emergency Department):

1. Reassurance and Environment: Move to quiet room; calm, supportive approach
2. Breathing Control: Guide slow diaphragmatic breathing (4 seconds in, hold 4 seconds, 4 seconds out)
3. Exclude Medical Emergency: Brief cardiac and pulmonary assessment; ECG if indicated
4. Pharmacological (if severe/prolonged):
   • Lorazepam 0.5-1mg PO/SL/IM (single dose)
   • Avoid routine benzodiazepine prescriptions
5. Psychoeducation: Explain panic physiology; reassure about non-dangerous nature
6. Safety Planning: Assess suicide risk; provide crisis contacts
7. Follow-up: Arrange primary care or mental health follow-up within 1-2 weeks

For Severe Anxiety with Suicidal Ideation:

• Immediate psychiatric consultation
• One-to-one observation
• Remove access to means
• Formal risk assessment (C-SSRS)
• Consider psychiatric admission if high risk

8.3 Psychological Therapies

Cognitive Behavioral Therapy (CBT) — FIRST-LINE for all anxiety disorders [7,8]

Evidence: Meta-analyses demonstrate effect sizes of 0.8-1.3 for CBT vs. waitlist controls across anxiety disorders. [18] Treatment gains maintained at 12-24 month follow-up.

Format: Individual or group; typically 12-16 sessions; protocol-based manualized treatment

Disorder-Specific CBT Emphases:

• GAD: Worry exposure; intolerance of uncertainty modification; problem-solving
• Panic Disorder: Interoceptive exposure; behavioral experiments; cognitive restructuring of catastrophic misinterpretation
• Social Anxiety: Behavioral experiments in social situations; attention training; video feedback
• Specific Phobia: Graduated exposure hierarchy; in-vivo exposure; single-session treatment effective for simple phobias
• Agoraphobia: Graduated exposure to avoided situations; with or without therapist-accompanied exposure

Applied Relaxation — Alternative first-line for GAD [8] Technique involving progressive muscle relaxation and rapid relaxation skills applied in anxiety-provoking situations. Non-inferior to CBT for GAD in NICE evidence review.

Acceptance and Commitment Therapy (ACT) Third-wave CBT approach emphasizing acceptance of anxious thoughts rather than challenging content; focus on values-directed action despite anxiety. Growing evidence base; may be helpful for treatment-resistant cases.

8.4 Pharmacological Management

First-Line Medications: SSRIs and SNRIs [7,8]

Key Prescribing Principles:

1. Start low, go slow: Begin at half standard antidepressant dose due to initial activation/jitteriness
2. Warn about delayed onset: Therapeutic effects emerge at 2-4 weeks; full effect by 8-12 weeks
3. Warn about initial worsening: Anxiety may transiently increase in first 1-2 weeks
4. Duration: Continue for minimum 12 months after remission; longer if recurrent episodes
5. Discontinuation: Gradual taper over 4+ weeks to minimize discontinuation syndrome

Second-Line and Adjunctive Medications:

Treatment-Resistant Anxiety (After 2 adequate SSRI/SNRI trials):

Medications to Use with Caution or Avoid:

8.5 Benzodiazepine Prescribing Guidelines

If Benzodiazepines Must Be Used:

• Reserve for short-term crisis management only (maximum 2-4 weeks)
• Use lowest effective dose
• Document clear rationale and time-limited plan
• Provide psychoeducation about dependence risk
• Schedule definite review date
• Avoid in patients with substance use history
• Do not prescribe on repeat/ongoing basis

Benzodiazepine Selection (if indicated for short-term use):

8.6 Lifestyle and Complementary Interventions

8.7 Special Populations

Pregnancy and Breastfeeding:

• CBT is first-line (no fetal exposure)
• If pharmacotherapy required: sertraline preferred (most safety data)
• Avoid paroxetine in first trimester (cardiac malformation risk)
• Benzodiazepines: avoid if possible; floppy infant syndrome risk
• Discuss risks vs. benefits; untreated severe anxiety also carries fetal risks

Elderly:

• Start at lower doses; slower titration
• Avoid benzodiazepines (falls, cognitive impairment)
• SSRIs preferred; monitor for hyponatremia (SIADH)
• Shorter CBT protocols may be needed

Comorbid Substance Use Disorder:

• Treat both conditions concurrently
• Avoid benzodiazepines (high misuse potential)
• SSRIs safe and effective
• Integrated treatment programs optimal

Cardiovascular Disease:

• SSRIs are safe post-MI
• Sertraline has best evidence in cardiac population
• Avoid TCAs (cardiac toxicity)
• Treat anxiety to reduce cardiac risk

8.8 Treatment Duration and Discontinuation

Acute Phase: 8-12 weeks to achieve response Continuation Phase: 6-12 months post-remission for first episode; longer for recurrent Maintenance: Consider indefinite treatment for recurrent episodes (≥3) or severe residual symptoms

Discontinuation Protocol:

1. Achieve sustained remission (≥6 months symptom-free)
2. Taper gradually over minimum 4 weeks (longer if prolonged treatment)
3. Reduce by 25% every 2-4 weeks
4. Warn about discontinuation symptoms vs. relapse
5. Provide relapse prevention plan
6. Close follow-up during taper

Discontinuation Syndrome (especially with paroxetine, venlafaxine):

• Dizziness, nausea, headache, flu-like symptoms
• Electric shock sensations ("brain zaps")
• Irritability, insomnia
• Onset 2-4 days after stopping; typically resolves in 1-2 weeks
• Management: slower taper; temporarily increase dose if severe

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SECTION 9: Complications

9.1 Psychiatric Complications

9.2 Medical Complications

9.3 Treatment-Related Complications

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SECTION 10: Prognosis and Outcomes

10.1 Natural History (Untreated)

10.2 Outcomes with Treatment

Predictors of Good Outcome:

• Early treatment initiation
• Good treatment adherence
• Absence of avoidance behaviors
• Lower baseline severity
• Absence of comorbid personality disorder
• Strong social support
• Completion of full CBT course

Predictors of Poor Outcome:

• Delayed treatment (> 2 years from onset)
• Severe avoidance/agoraphobia
• Comorbid depression or substance use
• Personality disorder comorbidity
• Early onset
• History of childhood trauma
• Treatment non-adherence

10.3 Long-Term Functional Outcomes

• Occupational: 30-50% report significant work impairment; higher unemployment rates
• Social: Impaired relationships, social isolation (especially SAD)
• Quality of life: Significantly reduced across all domains
• Healthcare utilization: High service use continues even after diagnosis

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SECTION 11: Prevention and Screening

11.1 Primary Prevention

11.2 Screening Recommendations

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SECTION 12: Key Guidelines and Evidence

12.1 Major Clinical Guidelines

NICE Guideline NG116: Generalized Anxiety Disorder and Panic Disorder in Adults (2019, updated 2020) [8]

• Organization: National Institute for Health and Care Excellence (UK)
• Key Recommendations:
  • Stepped care model for anxiety management
  • CBT is first-line psychological therapy
  • SSRIs (sertraline) first-line pharmacotherapy
  • Benzodiazepines only for short-term crisis use (2-4 weeks maximum)
  • Do not use antipsychotics for GAD/panic
• Link: https://www.nice.org.uk/guidance/ng116

APA Practice Guideline for Treatment of Panic Disorder (2010, reaffirmed 2020) [7]

• Organization: American Psychiatric Association
• Key Recommendations:
  • CBT and SSRIs/SNRIs are Level I recommendations
  • Combined treatment may be superior
  • Benzodiazepines effective but not first-line due to dependence

WFSBP Guidelines for Anxiety Disorders (2023) [24]

• Organization: World Federation of Societies of Biological Psychiatry
• Key Recommendations:
  • SSRIs/SNRIs first-line for all anxiety disorders
  • Pregabalin alternative for GAD
  • CBT should be offered to all patients

12.2 Landmark Trials

CALM Trial (2010) [13]

• Design: Randomized controlled trial, n=1004
• Intervention: Coordinated Anxiety Learning and Management (CALM) vs. usual care
• Outcome: CALM achieved 60.7% response vs. 39.5% usual care (pless than 0.001)
• Impact: Demonstrated superiority of collaborative care integrating CBT and pharmacotherapy
• PMID: 20483971

STAR*D Anxiety Analysis (2008) [25]

• Design: Secondary analysis of STAR*D depression trial
• Key Finding: Patients with anxious depression have lower remission rates, more side effects, and require longer treatment
• Impact: Highlighted importance of addressing comorbid anxiety
• PMID: 18190331

Meta-analysis of CBT for Anxiety (Cuijpers et al., 2016) [18]

• Design: Meta-analysis of 144 studies
• Key Finding: Effect size d=0.84 vs. control; effects maintained at 12-month follow-up
• Impact: Established CBT as evidence-based first-line treatment
• PMID: 24607174

BALANCE Trial - Pregabalin for GAD (2010) [26]

• Design: RCT, n=454
• Intervention: Pregabalin vs. placebo vs. lorazepam
• Outcome: Pregabalin effective with anxiolytic effects within first week
• PMID: 16026622

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SECTION 13: Patient Explanation

13.1 What Are Anxiety Disorders?

Anxiety is a normal human emotion that helps protect us from danger. However, in anxiety disorders, this protective system becomes overactive—like a smoke alarm that goes off for burnt toast rather than a real fire. Your brain is signaling "danger" even when there is no actual threat, causing your body to react with a racing heart, rapid breathing, and muscle tension.

13.2 What Causes Anxiety Disorders?

Anxiety disorders develop from a combination of factors:

• Genetics: Anxiety tends to run in families
• Brain chemistry: Imbalances in brain chemicals like serotonin
• Life experiences: Stressful events, especially in childhood
• Learned patterns: Habits of worry and avoidance

13.3 How Are They Treated?

Two main approaches work well, often best when combined:

Talking therapy (CBT): You'll learn to identify anxious thoughts, challenge them, and gradually face feared situations. This rewires the brain's anxiety response.

Medication: Antidepressant medications (SSRIs) help rebalance brain chemistry. They take 2-4 weeks to work and are not addictive.

13.4 What Can I Do to Help Myself?

• Regular exercise (30 minutes, 5 times weekly)
• Reduce caffeine and alcohol
• Practice relaxation or mindfulness
• Maintain regular sleep patterns
• Stay connected with supportive people
• Face fears gradually rather than avoiding them

13.5 What Is the Outlook?

Most people with anxiety disorders improve significantly with treatment. About 50-60% achieve full remission. The skills you learn in therapy stay with you and help prevent future episodes. Early treatment leads to better outcomes.

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SECTION 14: Examination Focus

14.1 Common Examination Questions

1. "What are the DSM-5 criteria for generalized anxiety disorder?"

   • Excessive worry more days than not for ≥6 months
   • Difficulty controlling worry
   • ≥3 associated symptoms (restlessness, fatigue, concentration difficulty, irritability, muscle tension, sleep disturbance)
   • Significant distress/impairment
   • Not due to substance or medical condition

2. "A 28-year-old woman presents with palpitations, dyspnea, and fear of dying during episodes lasting 10-30 minutes. What is your differential and management?"

   • Differential: Panic disorder, cardiac arrhythmia, hyperthyroidism, pheochromocytoma
   • Immediate: ECG, pulse oximetry, glucose, reassurance
   • Investigations: TSH, 12-lead ECG, consider Holter if paroxysmal
   • If panic disorder confirmed: CBT first-line, SSRI (sertraline 25mg increasing to 50-100mg)

3. "Describe the mechanism of action and evidence for SSRIs in anxiety disorders."

   • SSRIs inhibit serotonin reuptake, increasing synaptic 5-HT
   • Downstream effects include 5-HT1A receptor desensitization and neuroplastic changes
   • NNT approximately 5-7 for response vs. placebo
   • Effect size d=0.3-0.5 in meta-analyses
   • Time course: 2-4 weeks initial effect, 8-12 weeks full effect

4. "Differentiate social anxiety disorder from agoraphobia."

   • Social anxiety: Fear of scrutiny and negative evaluation by others
   • Agoraphobia: Fear of situations where escape difficult or help unavailable
   • Cognitive focus: Embarrassment/judgment vs. entrapment/panic-like symptoms

14.2 Viva Opening Statement

"Anxiety disorders are a group of mental disorders characterized by excessive fear and anxiety with associated behavioral disturbances. They are the most common mental disorders globally, with a lifetime prevalence of approximately 33%. The disorders include generalized anxiety disorder, panic disorder, social anxiety disorder, specific phobias, and agoraphobia. Management follows evidence-based guidelines with cognitive behavioral therapy and SSRIs as first-line treatments, and prognosis is generally favorable with appropriate intervention."

14.3 Common Mistakes to Avoid

• Failure to exclude medical causes before diagnosing primary anxiety
• Prescribing benzodiazepines as first-line or for long-term use
• Starting SSRIs at full dose (causes activation; start at half dose)
• Not warning patients about initial worsening and delayed onset of effect
• Forgetting to assess suicide risk in anxiety presentations
• Confusing social anxiety with agoraphobia (scrutiny vs. entrapment)
• Missing comorbid depression (always co-screen with PHQ-9)

14.4 Key Evidence to Cite

• CALM trial: Integrated care superior to usual care (PMID: 20483971)
• Cuijpers meta-analysis: CBT effect size d=0.84 with maintained gains (PMID: 24607174)
• NCS-R epidemiology: 33.7% lifetime prevalence (PMID: 15939837)
• NICE NG116: Stepped care, CBT first-line, SSRIs first-line pharmacotherapy

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SECTION 15: References

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2. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019. Lancet Psychiatry. 2022;9(2):137-150. doi:10.1016/S2215-0366(21)00395-3 [PMID: 35026139]

3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision. Washington, DC: American Psychiatric Publishing; 2022.

4. Craske MG, Stein MB. Anxiety. Lancet. 2016;388(10063):3048-3059. doi:10.1016/S0140-6736(16)30381-6 [PMID: 27349358]

5. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21(3):169-184. doi:10.1002/mpr.1359 [PMID: 22865617]

6. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593-602. doi:10.1001/archpsyc.62.6.593 [PMID: 15939837]

7. Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci. 2017;19(2):93-107. doi:10.31887/DCNS.2017.19.2/bbandelow [PMID: 28867934]

8. National Institute for Health and Care Excellence. Generalised anxiety disorder and panic disorder in adults: management. NICE guideline [NG116]. 2019 (updated 2020). https://www.nice.org.uk/guidance/ng116

9. de Lijster JM, Dierckx B, Utens EM, et al. The Age of Onset of Anxiety Disorders. Can J Psychiatry. 2017;62(4):237-246. doi:10.1177/0706743716640757 [PMID: 27310233]

10. McLean CP, Asnaani A, Litz BT, Hofmann SG. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J Psychiatr Res. 2011;45(8):1027-1035. doi:10.1016/j.jpsychires.2011.03.006 [PMID: 21439576]

11. Batelaan NM, Seldenrijk A, Bot M, van Balkom AJ, Penninx BW. Anxiety and new onset of cardiovascular disease: critical review and meta-analysis. Br J Psychiatry. 2016;208(3):223-231. doi:10.1192/bjp.bp.114.156554 [PMID: 26932485]

12. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092-1097. doi:10.1001/archinte.166.10.1092 [PMID: 16717171]

13. Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. JAMA. 2010;303(19):1921-1928. doi:10.1001/jama.2010.608 [PMID: 20483971]

14. Tyrer P, Baldwin D. Generalised anxiety disorder. Lancet. 2006;368(9553):2156-2166. doi:10.1016/S0140-6736(06)69865-6 [PMID: 17174708]

15. Huffman JC, Pollack MH. Predicting panic disorder among patients with chest pain: an analysis of the literature. Psychosomatics. 2003;44(3):222-236. doi:10.1176/appi.psy.44.3.222 [PMID: 12724504]

16. Lader M. Benzodiazepines revisited—will we ever learn? Addiction. 2011;106(12):2086-2109. doi:10.1111/j.1360-0443.2011.03563.x [PMID: 21714826]

17. Ribeiro JD, Huang X, Fox KR, Franklin JC. Depression and hopelessness as risk factors for suicide ideation, attempts and death: meta-analysis of longitudinal studies. Br J Psychiatry. 2018;212(5):279-286. doi:10.1192/bjp.2018.27 [PMID: 29587888]

18. Cuijpers P, Cristea IA, Karyotaki E, Reijnders M, Huibers MJ. How effective are cognitive behavior therapies for major depression and anxiety disorders? A meta-analytic update of the evidence. World Psychiatry. 2016;15(3):245-258. doi:10.1002/wps.20346 [PMID: 27717254]

19. Penninx BWJH. Anxiety disorders. Lancet. 2021;397(10277):914-927. doi:10.1016/S0140-6736(21)00359-7 [PMID: 33675836]

20. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1):169-191. doi:10.1038/npp.2009.83 [PMID: 19625997]

21. Nuss P. Anxiety disorders and GABA neurotransmission: a disturbance of modulation. Neuropsychiatr Dis Treat. 2015;11:165-175. doi:10.2147/NDT.S58841 [PMID: 25653526]

22. Charney DS. Neuroanatomical circuits modulating fear and anxiety behaviors. Acta Psychiatr Scand Suppl. 2003;(417):38-50. doi:10.1034/j.1600-0447.108.s417.3.x [PMID: 12950435]

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Last Reviewed: 2026-01-09 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Always consult current guidelines and local protocols. This content does not replace clinical judgment or patient-specific assessment.