Anxiety Disorders - A Comprehensive Overview

Definition

DSM-5 Classification

Note: PTSD and OCD were moved OUT of the anxiety disorders category in DSM-5 into their own separate chapters.

Individual Disorder Profiles

1. Panic Disorder

• Cardiopulmonary: palpitations, chest discomfort, shortness of breath
• Neurologic: dizziness, tremulousness, numbness/tingling
• Psychiatric: derealization, depersonalization, fear of losing control or dying
• GI: nausea

• Recurrent unexpected panic attacks
• At least 1 month of anticipatory anxiety ("worry about further attacks") OR behavioral change after the attacks
• At least some attacks must be "out of the blue" (unexpected)

2. Generalized Anxiety Disorder (GAD)

• Persistent, excessive, and/or unrealistic worry over multiple domains (minor matters included)
• Muscle tension, impaired concentration, autonomic arousal, feeling "on edge," restlessness, insomnia
• Duration: symptoms present most days for ≥6 months
• Onset usually before age 20

• 80% of patients with GAD also suffer from major depression, dysthymia, or social phobia

• Comorbid substance abuse (especially alcohol) is common

3. Social Anxiety Disorder (Social Phobia)

• Generalized - affecting many interpersonal situations
• Specific - e.g., public speaking, using public restrooms (performance anxiety)

4. Agoraphobia

5. Specific Phobia

Common Somatic Manifestations of Anxiety

Pathophysiology

• Serotonin (5-HT) - SSRI and SNRI efficacy demonstrates serotonergic and noradrenergic involvement
• GABA - Benzodiazepines enhance GABAergic inhibition, producing rapid anxiolysis
• Norepinephrine - Hyperactivation of the locus coeruleus contributes to somatic anxiety symptoms
• Glutamate - Alpha-2-delta (α2δ) ligands (pregabalin, gabapentin) modulate voltage-gated calcium channels on glutamatergic neurons

Diagnosis

1. Syndromic: Careful psychiatric history + mental status to determine pattern and fit to a specific disorder. Assess comorbidities.
2. Etiologic: Rule out secondary causes - medical conditions (thyroid disease, pheochromocytoma, cardiac arrhythmias), drug intoxication or withdrawal. Physical examination and labs (e.g., toxic drug screen, TFTs) are guided by clinical suspicion. - Goldman-Cecil Medicine

Treatment

Pharmacotherapy (Evidence-Based Monotherapy Recommendations)

• SSRIs/SNRIs: Preferred first line due to efficacy, safety, and effectiveness against comorbid depression. FDA-approved agents for GAD include escitalopram, paroxetine, venlafaxine, and duloxetine. Start at half the usual antidepressant dose (patients with anxiety are more sensitive to side effects). Allow 2-6 weeks for full effect.
• Benzodiazepines: Highly effective with rapid onset (hours vs. weeks). All theoretically equally effective; selection based on half-life. Long-acting agents (clonazepam, alprazolam XR) preferred over short-acting ones (lorazepam) to avoid rebound anxiety. NOT for patients with substance abuse history. Useful as short-term bridge during SSRI initiation.
• Buspirone: Non-sedating, non-addictive azapirone; takes 2-4 weeks for effect; useful in GAD.
• Pregabalin/Gabapentin (α2δ ligands): Approved for anxiety in Europe; used off-label in the US as augmenting agents. Good alternative to benzodiazepines in some patients.
• Beta-blockers: Used only for specific performance anxiety (e.g., public speaking), not as general anxiolytics.
• MAOIs: Effective especially for treatment-resistant panic disorder and social anxiety; limited by dietary tyramine restrictions and drug interactions. - Stahl's Essential Psychopharmacology; Harrison's 22E

Psychotherapy

• Cognitive component: Identifies and corrects dysfunctional automatic thoughts that trigger the anxiety cascade
• Behavioral component: Uses learning theory to extinguish avoidance behaviors and reinforce functional ones
• Exposure therapy: In vivo exposure is the treatment of choice for specific phobia
• CBT success rate for panic disorder: 75-85% in controlled trials
• CBT may be delivered individually, in group settings, or as part of family therapy

Recent Evidence

Prognosis and Duration of Treatment

• Antidepressant treatment should be maintained for 1-2 years after satisfactory response to prevent relapse (panic disorder)
• Anxiety disorders tend to have a chronic, relapsing course, particularly GAD
• First-degree relatives of GAD patients have a higher risk, indicating genetic/familial loading
• GAD and panic disorder segregate independently in family studies

Diagnosis of Generalized Anxiety Disorder (GAD)

DSM-5 Diagnostic Criteria

Criterion A - Core Feature

Criterion B

Criterion C - Associated Symptoms

Mnemonic: RICE-MI - Restlessness, Irritability, Concentration difficulty, Easy fatigue, Muscle tension, Insomnia

Criterion D - Functional Impairment

Criterion E - Medical Exclusion

Criterion F - Not Better Explained by Another Disorder

Clinical Manifestations

• Persistent, excessive, and/or unrealistic worry - often about minor matters - with life-disrupting effects
• Onset typically before age 20 years
• History of childhood fears and social inhibition may be present
• Unlike panic disorder, shortness of breath, palpitations, and tachycardia are relatively rare
• Worry is pervasive (multiple domains) rather than episodic or context-specific
• Patients feel they cannot "turn off" their worry
• Harrison's Principles of Internal Medicine 22E

Epidemiology

Differential Diagnosis

The most clinically challenging distinction is GAD vs. MDD - both have anxiety, worry, insomnia, and concentration difficulties. The presence of persistent anhedonia, prominent neurovegetative features, and hopelessness favors MDD. - Kaplan & Sadock's Comprehensive Textbook of Psychiatry

Diagnostic Workup

Clinical History

• Onset, duration, and severity of worry
• Number and type of worry domains
• Associated somatic and cognitive symptoms
• Functional impact (work, relationships, daily activities)
• History of trauma, substance use, medical conditions
• Family history of anxiety/depression

Physical Examination & Labs

• Thyroid function tests (TSH, free T4) - hyperthyroidism
• CBC, metabolic panel - rule out systemic illness
• Toxicology/drug screen - substance-related anxiety
• ECG if cardiac symptoms present
• Consider cortisol if Cushing's syndrome suspected

Screening Tools

• Cut-off ≥ 3 = positive screen
• Sensitivity 86%, Specificity 83% for GAD (LR+ 5.0, LR- 0.17)

• Cut-off ≥ 10: Sensitivity 89%, Specificity 82% (LR+ 5.1, LR- 0.13)
• Cut-off ≥ 5: Very sensitive (97%) - good for ruling OUT
• A GAD-7 < 5 also reduces probability of social anxiety disorder (sensitivity 88%) and panic disorder (sensitivity 94%)

The GAD-7 is validated for both screening and treatment monitoring. - Symptom to Diagnosis, 4th Edition; Kaplan & Sadock's

Important Clinical Points for Diagnosis

1. Suicide risk: Patients with GAD are at increased risk for suicide attempts - screen for suicidal ideation at every visit.
2. Comorbidities: Always assess for comorbid MDD, other anxiety disorders, and substance use - they are the rule, not the exception.
3. Course: GAD tends to fluctuate in severity. Higher symptom severity, longer duration of avoidance behavior, and high behavioral inhibition predict persistence.
4. Presentations in primary care: Patients commonly present with somatic complaints (headache, abdominal pain, palpitations) rather than directly reporting anxiety - a high index of suspicion is needed.
5. Atypical presentations requiring medical workup: Marked change in symptom intensity, atypical age of onset, or failure to respond to standard treatments should prompt broad medical assessment.

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry; Harrison's 22E

Recent Evidence on GAD-7 Screening