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Anxiety Disorders - Comprehensive Overview

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1. Definition & What Is an Anxiety Disorder?

• Excessive fear (a response to a real or perceived imminent threat)
• Excessive worry (apprehensive anticipation of future threats)

• Stahl's Essential Psychopharmacology, p. 375

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2. Classification (DSM-5-TR)

Note: OCD and PTSD are no longer classified as anxiety disorders in DSM-5, though they share overlapping symptom dimensions.

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3. Epidemiology

• Anxiety disorders are the most common class of psychiatric disorders
• ~1/3 of people meet criteria at some point in their lifetime
• Approximately 19% of U.S. adults are affected at any given time
• Disorders are highly comorbid - patients frequently have two or more anxiety disorders simultaneously, plus major depression (>80% comorbidity in GAD), dysthymia, or substance use disorders
• Early effective treatment can prevent the development of comorbid conditions
• Harrison's Principles of Internal Medicine 22E, p. 3700

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4. Neurobiology & Pathophysiology

The Fear Circuit

• Prefrontal Cortex / VMPFC - top-down regulation; suppresses amygdala output
• Hippocampus - contextual memory; stores fear memories and re-experiences (critical in PTSD)
• Amygdala - generates fear outputs; drives autonomic, endocrine, and behavioral responses
• CSTC loops (cortico-striato-thalamo-cortical) - generate the symptom of worry

Key Neurotransmitters

Fear Conditioning vs. Fear Extinction

• Fear conditioning: Synaptic strengthening in the amygdala following a threatening stimulus (long-term potentiation)
• Fear extinction: New learning that suppresses fear - VMPFC and hippocampus activate GABAergic interneurons in the amygdala's intercalated cell mass, gating fear output
• Fear extinction is more labile than fear conditioning - it can reverse over time ("renewal"), which explains relapse after CBT
• This is the neurobiological basis for exposure therapy
• Stahl's Essential Psychopharmacology, pp. 382-390

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5. Clinical Features by Disorder

Generalized Anxiety Disorder (GAD)

• Persistent, excessive, unrealistic worry about multiple life domains (work, health, finances)
• Symptoms: muscle tension, impaired concentration, restlessness/"on edge," insomnia, autonomic arousal
• Duration: ≥6 months, more days than not
• Lifetime prevalence: 5-6%; higher in first-degree relatives
• Unlike panic disorder - no short-lived episodic attacks; worry is chronic and pervasive

Panic Disorder

• Recurrent unexpected panic attacks: sudden surge of intense fear peaking within minutes
• Symptoms: palpitations, sweating, trembling, shortness of breath, chest pain, dizziness, derealization, fear of dying/losing control
• Followed by ≥1 month of anticipatory anxiety OR behavioral change (avoidance)
• Patients have heightened sensitivity to somatic symptoms - triggers a feedback loop escalating arousal

Social Anxiety Disorder (SAD)

• Marked fear of social/performance situations where scrutiny may occur
• Fear of acting in a way that will be humiliating or embarrassing
• Avoidance of social situations causes significant functional impairment

Specific Phobia

• Intense, irrational fear of a specific object or situation (heights, animals, blood, flying)
• Immediate anxiety response upon exposure; recognized as excessive by the individual

PTSD (now in "Trauma and Stressor-Related Disorders")

• Following exposure to actual/threatened death, serious injury, or sexual violence
• Four symptom clusters: intrusion, avoidance, negative cognitions/mood, hyperarousal/reactivity
• Hippocampal re-experiencing of traumatic memories activates the amygdala → fear response
• Harrison's Principles of Internal Medicine 22E, p. 2978-2990

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6. Diagnosis

1. Rule out medical causes - hyperthyroidism, pheochromocytoma, cardiac arrhythmias, hypoglycemia, substance use/withdrawal
2. Screening tools: GAD-7 (most validated), PHQ for comorbid depression, PRIME-MD
3. Duration thresholds: GAD ≥6 months; specific phobia/SAD symptoms persistent
4. Assess comorbidities: depression, substance use, other anxiety disorders
5. Rule out substance-induced anxiety: caffeine, stimulants, corticosteroids, thyroid hormone, alcohol withdrawal

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7. Treatment

Pharmacological

• Start SSRIs at 1/3 to 1/2 normal antidepressant dose (e.g., fluoxetine 5-10 mg, sertraline 25-50 mg, venlafaxine 37.5 mg)
• Maintain treatment 1-2 years after response to prevent relapse

• Benzodiazepines: positive allosteric modulation at GABA-A receptors in the amygdala and CSTC circuits → reduce fear and worry
• α2δ ligands: bind to presynaptic VSCCs → reduce excessive glutamate release → blunt amygdala hyperactivity

Psychological / Non-pharmacological

Treatment Approach Summary

1st line:  SSRI or SNRI + CBT (combined > monotherapy)
Acute relief: Short-term benzodiazepine while awaiting SSRI effect
GAD-specific: Buspirone or pregabalin as alternatives
Refractory: Augmentation (aripiprazole, valproate) or MAOI
Duration: Minimum 1-2 years after remission

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8. Special Considerations

• Comorbid depression: Very common (>80% in GAD); SSRIs/SNRIs treat both
• Substance use: Screen carefully - alcohol and benzodiazepines used for self-medication create dependence
• Pregnancy: Psychotherapy preferred; weigh risks of pharmacotherapy individually
• Children/adolescents: CBT is first-line; SSRIs second-line; ADHD is a common comorbidity with anxiety (PMID: 40245462)
• CBD: A 2024 systematic review and meta-analysis (PMID: 38924898) examined CBD for anxiety; evidence is emerging but not yet sufficient for routine recommendation

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9. Prognosis

• Anxiety disorders are chronic but treatable
• Early treatment reduces comorbidity risk
• Combined pharmacotherapy + CBT produces superior outcomes vs. either alone
• Relapse is common if treatment is stopped prematurely
• Fear extinction is more labile than fear conditioning - long-term behavioral maintenance strategies are important

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• Harrison's Principles of Internal Medicine 22E (2025), Chapter 463
• Stahl's Essential Psychopharmacology - Neuroscientific Basis, Chapter 8
• MSD Manual Professional Edition - Overview of Anxiety Disorders

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Anxiety in Anesthesia and Surgery

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1. Prevalence & Clinical Significance

• 40-85% of patients are apprehensive before surgery (depending on assessment method) - Barash's Clinical Anesthesia, p. 1803
• Up to two-thirds of ambulatory surgery patients show symptoms of anxiety - Miller's Anesthesia 10e
• Up to 30% of patients suffer from anesthesia-related preoperative anxiety, whether the procedure is elective or emergent
• 10% of surgical patients have a diagnosed generalized anxiety disorder - NYSORA / Rolfzen et al., Anesthesiology 2024

Why It Matters - Consequences of Unmanaged Perioperative Anxiety

• Cummings Otolaryngology, PMC11901026

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2. Risk Factors for Perioperative Anxiety

• Patient factors: Pre-existing anxiety disorder, depression, somatization, fearful temperament, poor sleep night before surgery
• Surgical factors: Type of surgery (ophthalmology, ENT - highest risk for emergence delirium), emergency vs. elective (both are equally affected for preoperative anxiety)
• Systemic factors: Poor information/communication; surgery in public vs. private hospital; ASA class III/IV
• Social factors: Lack of family support; previous negative hospital experiences
• Pediatric-specific: Age 2-7 years highest risk; separation anxiety peaks at age 1-3; adolescents may mask anxiety despite high internal distress

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3. Preoperative Assessment

• GAD-2 / GAD-7 - brief, validated tools
• PHQ-2 - for comorbid depression
• Modified Yale Preoperative Anxiety Scale (mYPAS) - standard in pediatric anesthesia
• Pre-anesthesia evaluation clinics: An anesthesiologist-led preoperative evaluation clinic is associated with reduced anxiety, improved acceptance of regional anesthesia, fewer day-of-surgery cancellations, and shorter hospital stay - Miller's Anesthesia 10e

Key insight: A preoperative consultation more than 2 weeks before surgery can reduce anxiety and improve satisfaction, especially when the same anesthesiologist who consulted also provides intraoperative care. More patients were adequately prepared by a preoperative interview than by 2 mg/kg pentobarbital IM given 1 hour before surgery. - Barash's Clinical Anesthesia, p. 1803

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4. Management of Perioperative Anxiety

A. Psychological / Non-Pharmacological (First-Line)

Important: Preoperative depressant drugs should never be used as a substitute for a comforting and tactful preoperative visit. - Barash's Clinical Anesthesia

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B. Pharmacological (Anxiolytic Premedication)

Adults

Meta-analysis: No evidence that anxiolytic premedication delays discharge in ambulatory patients, though some psychomotor impairment exists. Recovery primarily depends on other factors (type of anesthetic, duration).

Children

Note: Oral midazolam itself can provoke anxiety in children - giving the child a small toy first significantly reduces this. Distraction/play therapy is often equivalent or superior.

• Miller's Anesthesia 10e, pp. 9973-9975

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5. Patients with Pre-Existing Anxiety Disorders on Chronic Medications

Continuing Existing Medications

• SSRIs/SNRIs: Generally continue perioperatively unless contraindicated by NPO status. Sudden cessation causes withdrawal (flu-like symptoms, "brain zaps") or relapse
• Benzodiazepines (chronic use): Continue - abrupt withdrawal risks seizures and severe rebound anxiety
• Buspirone: Continue when possible
• MAOIs: Require special planning - interactions with many anesthetic agents (meperidine/serotonin syndrome; indirect sympathomimetics)

Drug Interaction Risks

Perioperative Phase-Specific Management

• Screen with PHQ-2/GAD-2
• Medication reconciliation - continue psychiatric drugs
• Educate and counsel; involve family support

• Continue existing medications when possible
• Coordinate with psychiatry if complex
• Avoid serotonin-augmenting anesthetics in SSRI patients
• For hypotension: prefer phenylephrine over ephedrine in MAOI patients

• Reassess mental status (brief tools)
• Resume all psychiatric medications as soon as oral intake resumes
• Higher risk for emergence delirium, postoperative cognitive dysfunction, and acute pain
• Consider structured psychological support; telehealth follow-up

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6. Special Populations

Pediatric Patients

• <9 months: Respond to surrogates (rocking, soothing)
• 1-3 years: Separation anxiety - distraction + parental surrogates
• 3-6 years: Fear of bodily harm - reassurance + play therapy
• 7-12 years: Want explanation + active participation; VR, videos highly effective
• Adolescents: May mask anxiety; screen carefully; risk factors include baseline anxiety, depression, somatization

Elderly / Cognitive Impairment

• Higher risk of emergence delirium and postoperative cognitive dysfunction
• Minimize benzodiazepines (Beers Criteria)
• Dexmedetomidine preferred for sedation/anxiolysis

Regional Anesthesia

• Pre-anesthesia evaluation clinics improve acceptance of regional anesthesia
• Regional techniques may themselves reduce anxiety by providing better pain control
• Anxiolytic premedication facilitates patient cooperation for block placement

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7. Summary Algorithm

Perioperative Anxiety Management
│
├── PREOP: Screen (GAD-2/PHQ-2) → Risk stratify
│       │
│       ├── Non-pharmacological (ALL patients):
│       │     • Preoperative visit + education
│       │     • Music, VR, distraction
│       │     • Family involvement
│       │
│       └── Pharmacological (selected patients):
│             Adults: IV midazolam pre-induction
│             Children: Oral midazolam 0.2 mg/kg OR
│                       Intranasal dexmedetomidine
│
├── INTRAOP: Continue chronic psych meds
│            Check drug interactions (SSRIs, MAOIs)
│            Sympathomimetic selection in MAOI patients
│
└── POSTOP: Resume meds ASAP
            Monitor for delirium/PCOD
            Structured psychological support
            Mental health follow-up at discharge

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• Miller's Anesthesia 10e - Management of Anxiety, Perioperative Anxiety in Children
• Barash's Clinical Anesthesia 9e - Psychological Preparation/Premedication
• Rolfzen ML et al. Management of Depression and Anxiety in Perioperative Medicine. Anesthesiology 2024;141:765-778
• Bello CM et al. Perioperative Anxiety: Current Status and Future Perspectives. PMC 2025
• Li H et al. Virtual Reality for Preoperative Anxiety. J Med Internet Res 2025 - PMID 40305092

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Perioperative Management of Diabetes Mellitus During Anaesthesia

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1. Why This Matters - The Metabolic Stress Response

• Counterregulatory hormones released: Cortisol, glucagon, growth hormone, catecholamines
• Net effects: Reduced insulin secretion, increased insulin resistance, elevated lipolysis and proteolysis, hyperglycaemia
• Anaesthesia and surgery interrupt normal meal and insulin schedules

Consequences of Uncontrolled Perioperative Hyperglycaemia

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2. Preoperative Assessment & Optimization

History & Examination

• Type of diabetes (T1DM vs T2DM), duration
• Current medications: insulin type/regimen, OHAs, CGM/insulin pump use
• HbA1c - marker of medium-term glycaemic control
• Diabetic complications:
  • Cardiovascular: CAD, autonomic neuropathy, orthostatic hypotension
  • Renal: Nephropathy - affects drug dosing, contrast use
  • Neuropathy: Autonomic neuropathy → gastroparesis → aspiration risk
  • Retinopathy: Eye protection intraoperatively

Key Laboratory Investigations

• Blood glucose (immediate)
• HbA1c - if >8% (T1DM) or >7% (T2DM) → consider delaying elective surgery
• Serum electrolytes (hypokalaemia common)
• Serum creatinine / eGFR (affects metformin, contrast, SGLT2 decisions)
• Urine ketones (especially T1DM)
• ECG (silent MI common in diabetic autonomic neuropathy)

When to Delay Elective Surgery

• HbA1c above target range (>8% T1DM, >7% T2DM)
• Abnormal electrolytes
• Ketonuria / DKA / HHS
• Uncontrolled hyperglycaemia without a sustainable plan

Scheduling

• Schedule as the first case of the day - minimises fasting duration, reduces glycaemic variability
• Arrive early in the morning; check blood glucose on arrival

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3. Perioperative Blood Glucose Targets

Key principle: Glucose trends are more important than single readings. Premixed insulin regimens should be avoided - too high a risk of hypoglycaemia.

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4. Medication Management - What to Do With Each Drug Class

Insulin

Oral / Non-Insulin Antidiabetic Agents

SGLT2 inhibitor warning: Euglycaemic DKA is a serious perioperative risk - BG may appear "normal" while significant ketoacidosis is developing. Always check ketones if a patient has been on an SGLT2 inhibitor recently. [FDA label warning; StatPearls]

GLP-1 agonist warning: The ASA 2024 consensus guidance and 2025 ADS/ANZCA recommendations (PMID 40814081) specifically address aspiration risk. These drugs delay gastric emptying and can cause significant gastric residue even after prolonged fasting. Consider full-stomach precautions if not held appropriately.

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5. Intraoperative Management

Blood Glucose Monitoring

• Check BG on arrival and then every 1-2 hours intraoperatively
• More frequent checks in complex/long cases
• CGM systems can be used with point-of-care BG meters (SAMBA 2024); accuracy may vary perioperatively (PMID 40613260) - do not rely on CGM alone without confirming with capillary BG

Insulin Administration

• Short, minor procedures (well-controlled T2DM): Sliding scale subcutaneous + hourly BG checks
• Major / long surgery, T1DM, poorly controlled T2DM: IV infusion of regular insulin
  • Run insulin infusion and dextrose as two separate infusions (easier to titrate than combined GIK)
  • Insulin infusion via side port on the same line as the dextrose infusion
  • Use a separate non-glucose isotonic fluid for volume replacement
• Target BG: 140-180 mg/dL (ADA) or <180 mg/dL (SAMBA)

Fluid Management

• Avoid dextrose-containing fluids as the sole resuscitation fluid in diabetic patients
• Use isotonic saline or balanced crystalloids (Ringer's/Hartmann's) for fluid replacement
• Hartmann's solution contains small amounts of lactate but is acceptable - not significantly hyperglycaemic

Treatment of Hyperglycaemia Intraoperatively

• BG 180-250 mg/dL: Insulin correction per sliding scale or infusion titration
• BG >300 mg/dL: IV insulin infusion mandatory
• Avoid correctional-only ("correction factor") insulin approach alone - too unpredictable

Treatment of Hypoglycaemia

• BG <70 mg/dL or symptomatic:
  • IV access in place: 50 mL of 50% dextrose (D50W) IV
  • No IV: Glucose tablet or clear juice (if awake)
  • Recheck BG in 15 minutes
  • Reduce insulin dose; investigate cause

Anaesthetic Considerations Specific to Diabetics

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6. Postoperative Management

Immediate Goals

• Ensure adequate BG control before discharge (ambulatory) or transfer (inpatients)
• Target BG 140-180 mg/dL (ADA); <200 mg/dL absolute upper limit
• Resume oral medications and diet as soon as possible

Resuming Medications

• Insulin: Restart usual regimen as soon as oral intake is established
• Metformin: Resume when eating normally and renal function confirmed stable (especially if contrast was used)
• SGLT2 inhibitors: Do not restart until wound healing is established and patient is eating normally
• GLP-1 agonists: Resume at next scheduled dose once tolerating oral intake
• Sulfonylureas/meglitinides: Resume with first meal

Key Postoperative Risks

PONV Prophylaxis

• Especially important in T1DM - PONV delays return to oral intake, risks DKA, and prevents resumption of the baseline insulin regimen

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7. Special Situations

Emergency Surgery

• No time for optimization - accept that glycaemia will not be ideal
• Check BG immediately; start IV insulin infusion if BG >180 mg/dL
• Hold ALL oral agents immediately
• Check for DKA/HHS - treat before or concurrent with surgery if life-threatening
• Aspiration precautions always (gastroparesis presumed possible)

T1DM vs T2DM Summary Differences

Insulin Pump (CSII) Management

• Continue for procedures <2 hours (coordinate with anaesthesiologist)
• Switch to IV infusion for longer or major operations
• Check institutional policy; requires patient ability to self-manage
• Recent studies show better glycaemic control (longer time-in-range) with pumps without increased hypoglycaemia or ketosis

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8. Summary Algorithm

PREOPERATIVE
│
├── Assess: Type, duration, HbA1c, complications, medications
├── Labs: BG, HbA1c, electrolytes, creatinine, ECG, urine ketones
├── Optimize: HbA1c <7-8% before elective surgery
├── Schedule FIRST CASE of the day
└── Medications:
      Stop: Sulfonylureas, meglitinides, SGLT2 (3-4 days), GLP-1 (1 day/1 week)
      Reduce: Long-acting insulin 20-25% night before
      Continue: Basal insulin (T1DM especially); metformin (minor procedures)

INTRAOPERATIVE
│
├── BG monitoring: on arrival, then every 1-2 hours
├── Target: 140-180 mg/dL
├── Short/minor: Sliding scale SC insulin
├── Long/major, T1DM: IV insulin infusion (separate from glucose infusion)
├── Fluids: Isotonic (not dextrose) for resuscitation
└── Special: Aspiration precautions, tilt test, padding, stiff joint assessment

POSTOPERATIVE
│
├── Resume oral intake + medications ASAP
├── PONV prophylaxis (especially T1DM)
├── BG monitoring every 4-6 hours until eating normally
├── Watch for: hypoglycaemia, wound infection, DKA, AKI, gastroparesis
└── Discharge: BG controlled; patient educated on medication resumption

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• Barash's Clinical Anesthesia 9e, Chapter 23 - Perioperative Glucose Management, p. 1781-1782
• StatPearls - Diabetic Perioperative Management (NIH/NCBI)
• Rajan N et al. SAMBA 2024 Updated Consensus Statement on Perioperative Blood Glucose Management. Anesth Analg 2024;139(3):459-477
• Hocking SL et al. 2025 ADS/ANZCA/GESA/NACOS Recommendations on peri-procedural GLP-1/GIP receptor agonists. PMID 40814081
• Jones IA et al. Perioperative Dexamethasone in Diabetic Patients (meta-analysis). Anesth Analg 2024 - PMID 39151134
• CPOC Guideline for Perioperative Care in Diabetes (Updated 2022)