Anxiety Disorders
Anxiety disorders are a group of mental health conditions characterized by excessive, persistent fear or worry that is disproportionate to the actual threat and causes significant functional impairment.
Anxiety disorders are a group of psychiatric conditions characterised by excessive, persistent fear and anxiety that is disproportionate to the actual threat, causes significant distress, and results in functional impairment [1][2]. The key distinction from normal anxiety — which is an adaptive, evolutionary survival response — is that in anxiety disorders, the fear response is out of proportion, persistent, and disabling.
Let's break down the terminology:
- Anxiety = a future-oriented emotional state characterised by apprehension and worry about potential threats (anticipatory)
- Fear = an immediate emotional response to a present or imminent threat (reactive)
- Both activate the same neurobiological "threat detection" circuitry, but anxiety disorders involve dysregulation of this system
Think of anxiety as your smoke alarm — useful when there's a real fire, but in anxiety disorders, the alarm goes off when you're just making toast.
Normal Anxiety vs. Pathological Anxiety
Normal anxiety is adaptive (e.g., motivating exam preparation). Pathological anxiety is distinguished by: (1) disproportionate intensity to the actual threat, (2) persistence beyond the stressor, (3) significant distress, and (4) functional impairment in social, occupational, or other domains.
The DSM-5-TR groups anxiety disorders as follows (note that OCD and PTSD are now in separate chapters since DSM-5, but are often taught alongside anxiety disorders for historical and clinical reasons):
- Generalised Anxiety Disorder (GAD)
- Panic Disorder
- Agoraphobia
- Social Anxiety Disorder (Social Phobia)
- Specific Phobia
- Separation Anxiety Disorder
- Selective Mutism
- Substance/Medication-Induced Anxiety Disorder
- Anxiety Disorder Due to Another Medical Condition
Anxiety disorders often have an early onset — teens or early twenties, show a 2:1 female predominance, have a waxing and waning course over lifetime, and are similar to major depression and chronic diseases such as diabetes in functional impairment and decreased quality of life. [1]
| Anxiety Disorder | One-Year Prevalence | Usual Age of Onset | Sex Ratio (F:M) |
|---|---|---|---|
| Generalised Anxiety Disorder | 2.8% | Variable: childhood to late adulthood | 2–3:1 |
| Panic Disorder (± agoraphobia) | 3.9% | Late adolescence to mid-30s | 2–3:1 |
| Social Phobia | 3.7% | Mid-teens | About equal |
| Specific Phobia | 4.4% | Childhood to adolescence | 2:1 |
| PTSD | 3.6% | Any age (after trauma) | 2:1 |
| OCD | 2.1% | Adolescence to early adulthood | Equal |
Table adapted from Narrow et al. 2002 [2]
Key epidemiological points:
- Most common mental disorders overall — lifetime prevalence ~30%
- Childhood anxiety disorders are the commonest mental disorders of childhood [2]
- Hong Kong context: Anxiety disorders are highly prevalent in Hong Kong, particularly GAD and social anxiety disorder. High population density, academic pressure (especially in adolescents), competitive work environments, and cultural factors (e.g., emphasis on face/"面子", stigma around mental health) contribute. The COVID-19 pandemic further increased prevalence.
- Comorbidity is the rule, not the exception: Anxiety disorders frequently co-occur with each other, with depression (>50% comorbidity), substance use disorders (especially alcohol as self-medication), and medical conditions [2]
High Yield — Comorbidity
When you see one anxiety disorder, actively look for others. GAD + MDD is extremely common ("anxious depression"). Panic disorder + agoraphobia co-occur in ~95% of agoraphobia cases. Substance misuse (particularly alcohol) is a frequent complication due to self-medication [2].
Risk Factors
Risk factors can be organised using the biopsychosocial model:
- Female sex (2:1 across most anxiety disorders) — likely related to hormonal factors (oestrogen modulates serotonergic and HPA axis function), greater amygdala reactivity, and psychosocial factors
- Family history / genetics (see Aetiology section for detail)
- Chronic medical illness (especially those causing autonomic symptoms — thyrotoxicosis, cardiac arrhythmias, COPD, asthma)
- Temperament of behavioural inhibition — a childhood temperamental trait of being timid and shy in novel situations, strongly predictive of later anxiety disorders
- Neuroticism — the personality trait of experiencing negative emotions easily; shared risk factor with depression [2][3]
- Early environment: parental separation, physical and sexual abuse, non-caring or overprotective parenting styles [3]
- Anxious attachment style — bidirectional escalation of anxiety in parent-child dyad [2]
- Cognitive biases — attentional bias towards threat, catastrophising, intolerance of uncertainty
- Lack of supportive networks, poorly functioning relationships, and poor social integration [3]
- Stress and trauma: long-term difficulties, recent life events (in particular events that lead to feelings of entrapment and humiliation) [3]
- Lower socioeconomic status
- Substance use (both as risk factor and consequence)
Anatomy and Neurocircuitry of Anxiety
Understanding the neuroanatomy is essential because it explains both the clinical features and the mechanisms of treatment. There are two key circuits to understand:
The amygdala is the central hub for processing fear. It is an almond-shaped ("amygdala" = Greek for "almond") structure in the medial temporal lobe [2].
Inputs to the amygdala:
- Thalamus → direct "quick and dirty" sensory relay (allows rapid fear response before conscious processing)
- Hippocampus → contextual memory cues ("I was attacked in this alley before") [2]
- Medial prefrontal cortex (mPFC) → top-down cognitive control and regulation of fear response [2]
Outputs from the amygdala (these explain the clinical features of anxiety):
| Amygdala Output | Target | Effect | Clinical Manifestation |
|---|---|---|---|
| Amygdala → Prefrontal cortex (orbitofrontal, anterior cingulate) | Cortex | Affect of fear, cognitive effects | Apprehension, worry, catastrophic thinking |
| Amygdala → Periaqueductal grey (PAG) | Brainstem | Fear behaviour (fight, flight, freeze) | Avoidance behaviour, agitation, freezing |
| Amygdala → Hypothalamus | HPA axis | Stress hormonal response (↑cortisol, ↑CRH) | Chronic stress effects, ↑medical comorbidity |
| Amygdala → Locus coeruleus | Brainstem | Autonomic response (↑noradrenaline release) | Palpitations, sweating, tremor, GI upset |
| Amygdala → Hippocampus | Temporal lobe | Fearful memory consolidation | Re-experiencing, conditioned fear responses |
Worry is mediated by the cortico-striato-thalamo-cortical (CSTC) loop [2]:
- Arises from the dorsolateral prefrontal cortex (DLPFC) → passes through striatum → thalamus → back to DLPFC
- This circuit is thought to account for recurrent, ruminative thoughts in anxiety disorders (e.g., ruminations, obsessions)
- Modulated by 5HT, GABA, DA, NA, glutamate [2]
- COMT polymorphisms may affect monoamine metabolism within this circuit → vulnerability to excessive worrying [2]
Two Circuits, Two Symptom Domains
Think of it this way: the amygdala circuit drives the fear and autonomic symptoms (palpitations, sweating, fight-or-flight), while the CSTC loop drives the worry and rumination (cognitive symptoms — "what if something terrible happens?"). Both are dysregulated in anxiety disorders.
| Brain Region | Normal Function | Abnormality in Anxiety |
|---|---|---|
| Amygdala | Registration of emotional significance of stimuli; development of emotional memory | Overactivation — exaggerated fear response [2] |
| mPFC / VMPFC | Cognitive control and regulation of amygdala; inhibitory role | Failure to recruit → inability to regulate excessive anxiety [2] |
| Hippocampus | Contextual memory cues for anxiety | Reduced volume (especially in PTSD); aberrant fear conditioning |
| Insula | Interoception (sensing internal body states) | ↑Activation → heightened awareness of bodily sensations (why patients "feel" their heart racing) |
| Dorsal ACC | Conflict monitoring, error detection | ↑Activation → excessive monitoring for threats |
| Locus coeruleus | Noradrenergic arousal | ↑Output → autonomic hyperarousal |
Neurochemical Basis of Anxiety
Dysregulation of the GABA, norepinephrine, and serotonin systems causes anxiety disorder [1].
- Inhibitory neurotransmitter [1]
- Suppresses other neurotransmitters e.g. serotonin, norepinephrine, dopamine etc. [1]
- GABA is the principal inhibitory neurotransmitter in the brain
- Mechanism: GABA-A receptors are chloride-channel-linked → when GABA binds → Cl⁻ influx → neuronal hyperpolarisation → ↓neuronal excitability
- In anxiety disorders: ↓GABA activity → failure to suppress amygdala and CSTC circuits → unchecked fear and worry responses
- Pharmacological implication: Benzodiazepines (BZDs) are positive allosteric modulators of GABA-A receptors → enhance GABA effect → rapid anxiolysis [2]
- Autonomic arousal and somatic symptoms in anxiety [1]
- Released from the locus coeruleus (LC) in the brainstem
- Mechanism: LC activation → widespread noradrenaline release → sympathetic activation → tachycardia, sweating, tremor, GI upset, pupil dilation
- In anxiety disorders: ↑central NA levels → autonomic hyperarousal
- Pharmacological implication: Long-term SNRIs → downregulation of adrenergic receptors → anxiolysis; β-blockers (e.g., propranolol) can block peripheral autonomic symptoms [2]
- Appetite, energy, sleep, mood, libido and cognitive function in anxiety [1]
- Serotonin innervates the amygdala and all elements of the CSTC circuit [2]
- Postulated role: signals presence of anxiety-producing stimuli but restrains associated behavioural responses — so serotonin is like a brake on anxiety behaviour
- In anxiety disorders: ↓cortical 5HT1A binding (demonstrated in panic disorder) → failure of this "braking" mechanism
- Pharmacological implication: SSRIs/SNRIs are first-line treatment — they increase serotonergic tone and restore the inhibitory modulation of anxiety [2]
- α₂δ ligands (e.g., pregabalin, gabapentin): bind α₂δ subunit of presynaptic voltage-sensitive calcium channels (VSCCs) → ↓release of excitatory neurotransmitters (especially glutamate) → anxiolytic effects [2]
- Glutamate: principal excitatory neurotransmitter; excessive glutamatergic activity in amygdala and CSTC circuit contributes to anxiety
- Dopamine: plays a role in CSTC circuit modulation; less directly implicated than 5HT/NA/GABA but relevant in certain anxiety-related conditions (e.g., social anxiety)
- HPA axis: chronic anxiety → sustained cortisol elevation → hippocampal damage (↓volume), immune dysregulation, metabolic effects
Exam Point: Neurotransmitter → Drug Mapping
- GABA → Benzodiazepines (agonists at GABA-A)
- Serotonin → SSRIs, SNRIs, buspirone (5HT1A partial agonist)
- Noradrenaline → SNRIs (long-term downregulation), β-blockers (peripheral)
- Glutamate (via α₂δ) → Pregabalin, gabapentin
- HPA axis → Not directly targeted but normalised by effective treatment
Aetiology (Biopsychosocial Model)
Biological Factors
- Twin studies: MZ > DZ concordance rate for anxiety disorders, but results are inconsistent and heritability is moderate (not as strong as schizophrenia or bipolar) [2]
- Shared heritability with other anxiety disorders, major depression, and neurotic personality — this explains why they so often co-occur [2]
- Specific gene profiles:
- 5HT transporter polymorphism (short allele of 5-HTTLPR → ↓serotonin reuptake efficiency → ↑vulnerability) [2]
- Glutamic acid decarboxylase (GAD65/67) polymorphism (enzyme converts glutamate → GABA; dysfunction → ↓GABA → ↑anxiety) [2]
- COMT polymorphisms → affects catecholamine metabolism → vulnerability to worrying [2]
- Heritability varies by disorder:
GAD:
- Neurochemistry: disturbances not consistently demonstrated [2]
- Functional imaging: inconsistent changes in amygdala reactivity, but altered activity in cortical regulatory regions (e.g., VLPFC) and altered connectivity with amygdala → inability to regulate excessive anxiety [2]
Panic Disorder:
- Structural: inconsistent changes in volumes of amygdala and cingulate cortex [2]
- Functional: abnormalities in baseline perfusion and during panic provocation in fear-related circuitry [2]
- Neurotransmitters: ↓cortical 5HT1A binding, ↓cortical GABA levels [2]
- Key structures: amygdala, dorsomedial hypothalamus/perifornical region (coordinates rapid mobilization of behavioural, autonomic, respiratory, and endocrine responses), insula, dorsal ACC, VMPFC [2]
Specific Phobia:
- ↑Activation of regions related to emotional appraisal and fear (amygdala, insula, ACC) [2]
- Failure to recruit VMPFC for regulation of limbic responses [2]
PTSD:
- Noradrenaline: ↑central NA levels with down-regulated central adrenergic receptors [2]
- HPA axis: ↓plasma cortisol with upregulation of glucocorticoid receptors, ↑CRH in CSF [2]
- Brain imaging: ↓hippocampus, left amygdala, ACC volume [2]
The PTSD HPA axis finding is counterintuitive: you'd expect ↑cortisol (as in chronic stress), but PTSD actually shows ↓cortisol with upregulated glucocorticoid receptors. This enhanced negative feedback "sensitises" the stress system, leading to exaggerated stress responses from smaller stimuli.
Psychological Factors
- Neuroticism: the tendency to experience negative emotions easily — shared vulnerability factor for both anxiety and depression [2][3]
- Behavioural inhibition: childhood temperamental trait of being timid and shy in novel situations — strongly predictive of later anxiety disorders (especially social anxiety) [2]
- Sociotropy (strong need for peer approval) — shared with depression [3]
- Anxiety sensitivity: tendency to fear anxiety-related sensations (e.g., fearing that palpitations mean a heart attack) — particularly relevant to panic disorder
Cognitive theories explain why anxiety becomes self-perpetuating:
- Coping style: worrying as a way to deal with potential threats — the person cannot relax until they have examined all possible dangers and identified potential solutions (this is GAD in a nutshell) [2]
- Cognitive bias: attention to potentially threatening stimuli, overestimation of environmental threat, preferential memory for threatening materials [2]
- Other cognitive styles: intolerance of uncertainty or ambiguity, meta-worry (worry about the consequences of excessive worrying) [2]
- Fear conditioning (classical conditioning): accounts for anxiety response associated with trauma-related cues with failure to extinguish conditioned responses — particularly relevant in phobias and PTSD [2]
- Cognitive theories of PTSD: overwhelming of normal processing of emotionally charged information → memories persist in an unprocessed form → can intrude into conscious awareness [2]
The cognitive model beautifully explains why anxiety disorders are self-maintaining: the person avoids the feared situation → never learns that the feared outcome doesn't occur → fear is maintained → further avoidance. This is why exposure is the core of CBT for anxiety.
Social Factors
- Lack of supportive networks, poorly functioning relationships, and poor social integration [3]
- Long-term difficulties, recent life events (especially entrapment and humiliation) [3]
- Lower socioeconomic status
- Hong Kong-specific: intense academic pressure (DSE exam culture), crowded living conditions, long working hours, limited mental health service access, and cultural stigma around help-seeking
Classification
| Category | Disorders |
|---|---|
| Anxiety Disorders | GAD, Panic Disorder, Agoraphobia, Social Anxiety Disorder, Specific Phobia, Separation Anxiety Disorder, Selective Mutism |
| Obsessive-Compulsive and Related Disorders (separate chapter since DSM-5) | OCD, Body Dysmorphic Disorder, Hoarding, Trichotillomania, Excoriation |
| Trauma- and Stressor-Related Disorders (separate chapter since DSM-5) | PTSD, Acute Stress Disorder, Adjustment Disorder |
Important Classification Change
A common exam pitfall: OCD and PTSD are NO LONGER classified under "Anxiety Disorders" in DSM-5/DSM-5-TR. They have their own separate chapters. However, they share overlapping neurocircuitry and are frequently tested alongside anxiety disorders.
ICD-11 (which has now replaced ICD-10) similarly separates anxiety disorders from OCD-related and stress-related disorders:
- 6B00 Generalised Anxiety Disorder
- 6B01 Panic Disorder
- 6B02 Agoraphobia
- 6B03 Specific Phobia
- 6B04 Social Anxiety Disorder
- 6B05 Separation Anxiety Disorder
- 6B06 Selective Mutism
| DSM-5 | ICD-10 (F93) |
|---|---|
| Separation anxiety disorder | Separation anxiety disorder of childhood |
| Specific phobia | Phobic anxiety disorder of childhood |
| Social anxiety disorder | Social anxiety disorder of childhood |
| Generalized anxiety disorder | — |
- Commonest mental disorders of childhood [2]
- Content of anxiety is influenced by developmental stage [2]:
- Infants: fear of strangers → social anxiety
- Preschool: fear of separation, specific objects → separation anxiety, specific phobias
- Early adolescence: fear of social situations / personal adequacy → social phobia
- Late adolescence: resembles adult patterns → GAD, panic disorders
- Diagnosis: only when developmentally inappropriate (more severe and prolonged than usual) and causes significant distress + functional impairment [2]
Clinical Features
The clinical features of anxiety disorders can be understood as the downstream effects of the neurocircuitry described above. A useful mnemonic for the core features is the 5 A's:
Apprehension, Arousal, Anticipatory anxiety, Avoidance, Autonomic activation [2]
Symptoms (Subjective — What the Patient Reports)
These arise from the CSTC worry circuit and amygdala → prefrontal cortex projections:
| Symptom | Pathophysiological Basis |
|---|---|
| Excessive worry / apprehension | Overactivity of CSTC loop → recurrent ruminative thoughts that cannot be suppressed; failure of mPFC regulatory control over amygdala |
| Feeling of dread / impending doom | Amygdala activation → direct projection to prefrontal cortex generating affect of fear |
| Difficulty concentrating | Prefrontal resources hijacked by worry circuit → ↓available cognitive capacity for other tasks |
| Irritability | Chronic amygdala activation and cortisol elevation → ↓threshold for emotional reactivity |
| Restlessness ("keyed up" or "on edge") | Sustained locus coeruleus activation → chronic heightened arousal state |
| Sleep disturbance (insomnia, especially difficulty falling asleep) | Failure to suppress amygdala and LC at night → hyperarousal prevents sleep initiation |
| Anticipatory anxiety | CSTC loop generates "what if" scenarios about future encounters with feared situations |
| Fear of losing control / going crazy / dying (particularly in panic disorder) | Catastrophic misinterpretation of autonomic symptoms — e.g., palpitations → "I'm having a heart attack" |
These arise primarily from the amygdala → locus coeruleus → sympathetic nervous system and amygdala → hypothalamus → HPA axis pathways:
| System | Symptom | Pathophysiological Basis |
|---|---|---|
| Cardiovascular | Palpitations, tachycardia | Sympathetic activation → ↑heart rate via β₁ adrenergic receptors on SA node |
| Chest pain/discomfort | Chest wall muscle tension (intercostals); hyperventilation-related coronary vasoconstriction | |
| Respiratory | Dyspnoea / sensation of choking | Hyperventilation driven by sympathetic activation of respiratory centres |
| Hyperventilation | ↑Respiratory rate → ↓pCO₂ → respiratory alkalosis → perioral tingling, lightheadedness | |
| Gastrointestinal | Nausea, "butterflies", abdominal discomfort | Sympathetic activation → ↓GI motility and blood flow diversion away from gut; vagal stimulation |
| Dry mouth | Sympathetic activation → ↓salivary gland secretion (salivary glands are predominantly parasympathetic) | |
| Difficulty swallowing (globus sensation) | Pharyngeal muscle tension | |
| Neurological | Tremor | ↑Noradrenaline → β₂ adrenergic activation of skeletal muscle |
| Dizziness / lightheadedness | Hyperventilation → ↓pCO₂ → cerebral vasoconstriction → ↓cerebral blood flow | |
| Paraesthesia (tingling in hands, feet, perioral) | Respiratory alkalosis from hyperventilation → ↓ionised Ca²⁺ → ↑neuronal excitability | |
| Headache | Sustained muscle tension (tension-type headache mechanism) | |
| Genitourinary | Urinary frequency / urgency | Autonomic activation of detrusor muscle |
| Musculoskeletal | Muscle tension, aching | Sustained sympathetic-mediated muscle contraction (especially neck, shoulders, back) |
| Dermatological | Sweating (diaphoresis) | Sympathetic cholinergic fibres to eccrine sweat glands |
| Flushing / pallor | Sympathetic vasomotor changes — vasoconstriction (pallor) or vasodilation (flushing) | |
| General | Fatigue / exhaustion | Chronic hyperarousal depletes energy reserves; sustained cortisol elevation → metabolic effects |
Why Hyperventilation Causes Tingling
Hyperventilation → ↓CO₂ → respiratory alkalosis → ↑pH → albumin releases H⁺ to buffer → binds more Ca²⁺ → ↓free ionised Ca²⁺ → ↑neuronal membrane excitability → perioral and peripheral paraesthesia, even carpopedal spasm (Trousseau's sign equivalent). This is why breathing into a paper bag (↑CO₂ rebreathing) helps.
| Sign | Pathophysiological Basis |
|---|---|
| Tachycardia | Sympathetic β₁ activation of SA node |
| Tachypnoea / hyperventilation | Sympathetic activation of respiratory drive |
| Diaphoresis (sweating) | Sympathetic cholinergic eccrine gland activation |
| Tremor (fine, postural) | β₂-adrenergic skeletal muscle activation |
| Muscle tension (palpable on examination) | Sustained sympathetic motor activation |
| Restlessness / psychomotor agitation | Generalised arousal from locus coeruleus activation |
| Exaggerated startle response | Amygdala hyperactivation → ↓threshold for startle |
| Pallor or flushing | Sympathetic vasomotor tone changes |
| Pupillary dilation (mydriasis) | Sympathetic activation of dilator pupillae muscle |
| Dry mouth (observable if patient licks lips, has difficulty speaking) | ↓Parasympathetic salivation |
| Feature | Explanation |
|---|---|
| Avoidance behaviour | Core maintaining factor — patient avoids feared situations → never learns feared outcome won't occur → fear persists. Driven by amygdala → PAG "flight" response |
| Safety behaviours | Subtle avoidance within situations (e.g., always sitting near exits, carrying medication "just in case") — maintains anxiety by preventing disconfirmation of fears |
| Reassurance-seeking | Reflects intolerance of uncertainty; provides transient relief but maintains the anxiety cycle |
| Substance use | Self-medication with alcohol, benzodiazepines, cannabis — ↓amygdala activation temporarily but worsens anxiety long-term (rebound, withdrawal) |
Disorder-Specific Clinical Features
Definition: Excessive, uncontrollable worry about multiple everyday concerns (work, health, family, finances, minor matters) occurring more days than not for ≥6 months (DSM-5) [2].
Core features:
- Pervasive, excessive worry about multiple topics — the worry is "free-floating" (not focused on one specific situation or object)
- Difficulty controlling the worry — the person recognises it's excessive but cannot stop
- Associated with ≥3 of: restlessness, easy fatigability, difficulty concentrating, irritability, muscle tension, sleep disturbance (DSM-5 criteria)
- The anxiety and worry cause clinically significant distress or functional impairment
- Not attributable to substance or medical condition
Pathophysiology-clinical correlation: GAD is thought to primarily involve the CSTC worry circuit with altered activity in cortical regulatory regions (e.g., VLPFC) and altered connectivity with amygdala → inability to regulate excessive anxiety [2]
Special features:
- Blood-injury phobia shows a unique vasovagal response: initial tachycardia → then bradycardia, pallor, dizziness, N/V, fainting (diphasic response) — contrast to the pure sympathetic activation seen in other anxiety disorders [2]
Definition: Recurrent, unexpected panic attacks — abrupt surges of intense fear/discomfort peaking within minutes, followed by persistent worry about future attacks or maladaptive behavioural changes [2].
Panic attack symptoms (≥4 of the following, peaking within minutes):
- Palpitations / tachycardia
- Sweating
- Trembling / shaking
- Shortness of breath / smothering
- Feelings of choking
- Chest pain / discomfort
- Nausea / abdominal distress
- Dizziness / lightheadedness / faintness
- Chills / hot flushes
- Paraesthesias (numbness / tingling)
- Derealisation / depersonalisation
- Fear of losing control / "going crazy"
- Fear of dying
Key distinguishing features:
- Unexpected: no obvious cue or trigger → can occur during sleep (nocturnal panic) or relaxation [2]
- Recurrent: at least one within one month
- Worry/behaviour change: persistent concern about additional attacks, worry about implications (heart attack, losing control), or significant maladaptive behaviour change (avoiding exercise, reorganising daily life) [2]
- These somatic symptoms may prompt help-seeking — patients often present to ED thinking they are having a heart attack or dying [2]
D/dx of panic attacks within anxiety disorders: Panic attacks can occur in ANY anxiety disorder, but are expected/predictable in those contexts (e.g., encountering feared object in phobia). Only in panic disorder are they truly unexpected [2].
Also known historically as: irritable heart, Da Costa's syndrome, neurocirculatory asthenia, disorderly action of the heart, effort syndrome [2]
Definition: Marked fear/anxiety about ≥2 of the following situations, due to concern that escape might be difficult or help might be unavailable if panic-like symptoms develop:
- Using public transportation
- Being in open spaces
- Being in enclosed places
- Standing in line / being in a crowd
- Being outside the home alone
Key features:
- The situations are actively avoided, require a companion, or endured with intense fear/anxiety
- Fear is out of proportion to actual danger
- Persists ≥6 months
- 95% comorbid with panic disorder [2]
- Lifetime prevalence: 1.1% (with PD), 0.8% (without PD) [2]
- Can exist independently of panic disorder in DSM-5 (a change from DSM-IV)
Definition: Marked fear/anxiety about social situations in which the individual is exposed to possible scrutiny by others [2].
Core features:
- Fear that they will behave in a way or show anxiety symptoms that will be negatively evaluated (humiliated, embarrassed, rejected, or offending others) [2]
- Fear is out of proportion to actual threat
- Can be generalised (widespread social situations) or performance-only (discrete triggers like public speaking) [2]
- Associated with: blushing, tremor, nausea, urinary urgency [2]
- Anticipatory anxiety and avoidance behaviour → significant distress and functional impairment [2]
- Onset: typically mid-teens as intensification of pre-existing shyness, or following stressful social experience [2]
- Course: only 50% seek treatment, usually after many years of symptoms [2]
D/dx from normal shyness: normal shyness tends to be less severe and pervasive, and associated with little distress and functional impairment [2]
Definition: Marked fear/anxiety about a specific object or situation [2].
Types: animal, natural environment, blood-injection-injury, situational, other
Core features:
- Fear recognised as completely irrational or excessive but unable to be controlled [2]
- Fear is intense/severe and out of proportion to actual danger [2]
- Evoked nearly every time individual contacts phobic stimulus [2]
- Associated with anticipatory anxiety and avoidance behaviour [2]
- Blood-injection-injury phobia: unique diphasic response — initial tachycardia → vasovagal response (↓HR, pallor, dizziness, N/V, fainting) [2]
Onset: generally mid-childhood/early adolescence; animals/blood-injury in childhood; situational/natural environment in late adolescence to early adulthood [2]
Recognising Anxiety That Is Secondary to Other Conditions
This is a critical clinical skill — not every anxious patient has a primary anxiety disorder.
The theme/focus of the anxiety helps identify the underlying diagnosis:
| Theme of Anxiety | Consider |
|---|---|
| Worry about gaining weight | Eating disorder |
| Worry about having serious illness | Illness anxiety disorder (hypochondriasis) |
| Fear of being poisoned or killed | Paranoid schizophrenia (delusional beliefs) |
| Ruminatory thoughts of guilt or worthlessness | Depression |
| Associated with obsessional thoughts or compulsions | OCD |
| Fear of separation or abandonment | Borderline or dependent PD |
| Fear of being rejected or inadequate | Avoidant PD |
| Mechanism | Examples |
|---|---|
| Autonomic symptoms | Thyrotoxicosis, hypoglycaemia (episodic), phaeochromocytoma (episodic) |
| Dyspnoea | Heart failure, PE, COPD, asthma |
| Others | Cerebral trauma, BPSD of dementia, malignancies, Cushing's disease, temporal lobe epilepsy |
| Mechanism | Examples |
|---|---|
| Intoxication | Alcohol, stimulants (amphetamines, cocaine, caffeine), cannabis, inhalants, hallucinogens (PCP) |
| Withdrawal | Alcohol, sedatives/hypnotics (BZDs, opiates), caffeine, cocaine, nicotine |
| Side effects of drugs | Antidepressants (especially first 2 weeks), corticosteroids, sympathomimetics, T₄, compound analgesics with caffeine, anticholinergics, antipsychotics (akathisia) |
Common Exam Trap
Always rule out medical causes of anxiety before diagnosing a primary anxiety disorder. The classic ones to remember: thyrotoxicosis, hypoglycaemia, phaeochromocytoma, PE, cardiac arrhythmias (SVT), and drug withdrawal (especially alcohol and benzodiazepines). A TFT and glucose are minimum investigations.
- Mild depression often co-exists with and cannot be separated from anxiety disorders
- Very commonly seen in primary care (6.9% prevalence) [2]
- Commonly present with prominent somatic symptoms to healthcare
- Mood symptoms: anxiety, depression, irritability
- Somatic symptoms: fatigue, insomnia, somatic symptoms and bodily preoccupation
- Cognitive symptoms: poor concentration
- May cause disabling difficulties in personal and occupational function
- Waxing and waning course over lifetime [1]
- Panic disorder: remission in 64% at 2 years; mean time to remission 5.7 years [2]
- Good prognostic factors: female, no ongoing stressors, subthreshold panic, no comorbid depression/agoraphobia/PD [2]
- GAD: tends to be chronic with fluctuating severity
- Social anxiety disorder: chronic; only 50% seek treatment [2]
- Specific phobia: tends to be lifelong when untreated [2]
- Childhood anxiety: ~2/3 disappear in 3-5 years, but ~1/3 will develop other anxiety disorders at follow-up [2]
- Impact: decreased QoL, functional impairment, and all-cause mortality (especially cardiovascular disorders) [2]
High Yield Summary
Definition: Anxiety disorders = excessive, persistent, disproportionate fear/anxiety → distress + functional impairment.
Epidemiology: Most common psychiatric disorders; early onset (teens-20s); F:M = 2:1; high comorbidity with depression and substance use.
Two key circuits: (1) Amygdala-based fear circuit → autonomic/somatic symptoms; (2) CSTC loop → worry/rumination.
Three key neurotransmitters: GABA (inhibitory, ↓ in anxiety → BZDs), serotonin (restrains anxiety behaviour → SSRIs), noradrenaline (autonomic arousal → SNRIs, β-blockers).
5 A's of anxiety: Apprehension, Arousal, Anticipatory anxiety, Avoidance, Autonomic activation.
Aetiology: Biopsychosocial — genetics (moderate, shared with depression), neurobiological (amygdala overactivation, mPFC failure), personality (neuroticism, behavioural inhibition), cognitive biases, early adversity, social factors.
Always rule out: Medical causes (thyrotoxicosis, hypoglycaemia, phaeochromocytoma, PE, arrhythmia), substance intoxication/withdrawal, medication side effects.
DSM-5 classification: GAD, panic disorder, agoraphobia, social anxiety disorder, specific phobia, separation anxiety disorder, selective mutism. OCD and PTSD are in SEPARATE chapters.
Panic attacks can occur in any anxiety disorder but are only "unexpected" in panic disorder.
Blood-injection-injury phobia = unique diphasic vasovagal response (not pure sympathetic).
Active Recall - Anxiety Disorders (Pre-DDx/Dx/Mx)
[1] Lecture slides: GC 167. I feel very nervous Anxiety disorders.pdf (p7, p16) [2] Senior notes: ryanho-psych.md (Sections 8.1 Anxiety Disorders, 8.1.3 Panic Disorder, 8.1.4 Phobic Anxiety Disorders, 8.2 PTSD aetiology, 12.5 Childhood Anxiety Disorders, Epidemiology table) [3] Lecture slides: GC 164. I am depressed Mood disorders.pdf (p12 — aetiology psychosocial hypothesis, shared risk factors)
Differential Diagnosis of Anxiety Disorders
The differential diagnosis of anxiety disorders is one of the most clinically important skills in psychiatry — and, frankly, in all of medicine. The reason is simple: anxiety symptoms are ubiquitous. They appear in virtually every psychiatric disorder, in dozens of medical conditions, and as effects of substances and medications. Your job is to work out what is driving the anxiety.
The approach is hierarchical and systematic. Think of it as peeling an onion — start with the most dangerous/treatable causes (organic, substance-related), then move to other psychiatric disorders, and only then settle on a primary anxiety disorder.
The Diagnostic Hierarchy for Anxiety
Always follow the diagnostic hierarchy [2]: Organic → Substance-induced → Psychotic disorders → Mood disorders → Anxiety disorders → Personality disorders. A higher-order diagnosis takes precedence because treating it often resolves the anxiety symptoms. Only diagnose a primary anxiety disorder when higher-order causes have been excluded or cannot fully explain the presentation.
Before diagnosing any primary anxiety disorder, you must exclude medical conditions that can mimic anxiety. The reason is that these conditions produce genuine autonomic symptoms (palpitations, sweating, tremor, dyspnoea) through direct physiological mechanisms — the patient isn't "anxious" in the psychiatric sense; their body is generating alarm signals from an organic source.
Physical disorders to exclude [1][2]:
| System | Condition | Why It Mimics Anxiety | Distinguishing Clue |
|---|---|---|---|
| Endocrine | Thyroid disease (thyrotoxicosis) | ↑T₃/T₄ → ↑sympathetic sensitivity → tachycardia, tremor, sweating, weight loss, heat intolerance | Persistent autonomic symptoms even at rest; weight loss despite ↑appetite; goitre; abnormal TFTs |
| Endocrine | Hypoglycaemia | ↓Glucose → counter-regulatory catecholamine surge → sweating, tremor, palpitations, anxiety | Episodic, temporally related to fasting/meals; resolves with glucose; finger-prick glucose confirms |
| Endocrine | Phaeochromocytoma | Catecholamine-secreting tumour → episodic surges of adrenaline/noradrenaline → severe palpitations, sweating, hypertension, headache | Episodic "attacks" with marked hypertension; 24h urinary catecholamines/metanephrines diagnostic |
| Endocrine | Cushing's disease | ↑Cortisol → anxiety, insomnia, mood disturbance | Cushingoid features; 24h urinary cortisol; dexamethasone suppression test |
| Endocrine | Hyperparathyroidism | ↑Ca²⁺ → neuropsychiatric symptoms including anxiety | Elevated serum calcium; "bones, stones, groans, moans" |
| Cardiovascular | Cardiac disease (arrhythmias, SVT) | Rapid/irregular heartbeat → palpitations perceived as anxiety | Episodic; ECG/Holter captures arrhythmia; may have syncope |
| Cardiovascular | Heart failure, PE | Dyspnoea → sensation of breathlessness interpreted as anxiety | Orthopnoea, JVP elevation, leg swelling (HF); pleuritic chest pain, haemoptysis, Wells score (PE) |
| Neurological | Epilepsy (especially temporal lobe) | Ictal fear as aura; déjà vu; automatisms | Stereotyped episodes; post-ictal confusion; EEG abnormalities |
| Neurological | Vestibular dysfunction | Dizziness/vertigo → anxiety; may trigger panic attacks | Positional component; nystagmus on examination |
| Respiratory | COPD, asthma | Dyspnoea and air hunger → anxiety | Wheeze, prolonged expiratory phase; spirometry abnormal |
| Other | Cerebral trauma, BPSD of dementia, malignancies | Various mechanisms including direct neurological effects | Focal neurology, cognitive decline, constitutional symptoms |
Substance abuse — intoxication or withdrawal [1][2]:
| Mechanism | Substances |
|---|---|
| Intoxication | Alcohol, stimulants (amphetamines, cocaine, caffeine), cannabis, inhalants, hallucinogens (PCP) |
| Withdrawal | Alcohol (can be life-threatening), sedatives/hypnotics (BZDs, opiates), caffeine, cocaine, nicotine |
| Side effects of medications | Antidepressants (especially first 2 weeks — paradoxical anxiety), corticosteroids, sympathomimetics, T₄, compound analgesics with caffeine, anticholinergics, antipsychotics (akathisia) |
Key distinguishing clue: Anxiety that occurs only in the context of substance use and is most severe in the morning (when withdrawal is typically most severe) points towards substance-induced anxiety [2].
Why antidepressants cause initial anxiety: SSRIs initially flood serotonin receptors including the anxiogenic 5HT2C receptors before adaptive downregulation occurs (~2 weeks). This is why the advice is to "start low, go slow" and warn patients about initial worsening.
Step 3: Differentiate Among Anxiety Disorders Themselves
This is where the exam really tests you. The core trick is to identify what the patient fears and when — the focus of fear and the pattern of anxiety distinguish one anxiety disorder from another.
The major anxiety-related disorders can be mapped by what they fear [1]:
Now let us go through each differential in detail.
A. Differentiating Between Primary Anxiety Disorders
| Feature | GAD | Panic Disorder |
|---|---|---|
| Pattern | Continuous, pervasive worry | Episodic, discrete panic attacks |
| Nature of attack | Panic attacks can occur (from escalating worry) but are expected/cued | Panic attacks are unexpected (no obvious trigger) — can occur during sleep or relaxation |
| Content of worry | Persistent worry about multiple chronic, non-specific complaints (finances, health, family, work) | Calamitous thoughts about acute life-threatening illness ("I'm dying", "I'm going mad"), anticipatory anxiety about next attack |
| Somatic focus | Multiple organ systems, chronic | Acute, dramatic autonomic surge peaking within minutes |
| ICD-10 note | GAD is NOT diagnosed if criteria for panic disorder are met (GAD is a diagnosis of exclusion in ICD-10) | Takes precedence over GAD in ICD-10 |
| DSM-5 note | Can be comorbid with panic disorder in DSM-5 | Can be comorbid with GAD in DSM-5 |
| Feature | GAD | Social Anxiety Disorder |
|---|---|---|
| Focus of worry | Widespread — not focused on a specific issue (finances, health, relationships, work, trivial matters) | Specifically concerns social situations where the person can be observed, scrutinised, or evaluated |
| Context | Anxious whether or not being evaluated | Anxious specifically when being evaluated or in anticipation of social situations |
| Social worries | May have social worries but focus is on nature of ongoing relationships rather than scrutiny | Focus is on fear of negative evaluation (humiliation, embarrassment, rejection) |
| Feature | GAD | OCD |
|---|---|---|
| Content of thoughts | Day-to-day worries (finances, work, health, family) — often realistic concerns, just excessive | Primal fears (contamination, harm, symmetry, blasphemy) — often bizarre, irrational, or magical |
| Nature of thoughts | Worries — ego-syntonic ("I can't help worrying about these things") | Obsessions — ego-dystonic ("these thoughts are intrusive and I don't want them") |
| Behaviours | Checking behaviours may occur but are directly related to preventing feared outcome and not usually excessive/time-consuming | Compulsions are ritualistic/rule-driven, may be unrelated to feared outcome (e.g., tapping three times to prevent harm), clearly excessive and time-consuming |
This is a critical distinction. Panic attacks can occur in almost any anxiety disorder, but the key question is: are they expected or unexpected?
| Disorder | Nature of Panic Attacks |
|---|---|
| Panic disorder | Unexpected — no obvious cue/trigger; can occur during sleep/relaxation |
| Specific phobia | Expected — triggered by encountering phobic stimulus |
| Social anxiety | Expected — triggered by social/performance situations |
| PTSD | Expected — triggered by trauma-related cues |
| OCD | Expected — triggered by contamination, intrusive thoughts |
| GAD | Expected — triggered by escalating worry |
| Separation anxiety | Expected — triggered by actual/anticipated separation |
"If panic attacks occur with agoraphobia, then the diagnosis should be agoraphobia with panic attacks instead of both disorders under ICD-10" [2]. In DSM-5, both can be coded separately.
| Feature | Specific Phobia | Agoraphobia | Social Anxiety |
|---|---|---|---|
| Focus of fear | Particular circumscribed stimulus (animal, blood, flying, heights) | Fear of panic symptoms / unavailability of help/escape — same fear across multiple situations | Fear of scrutiny, embarrassment, negative evaluation |
| Situation specificity | Highly specific (one or a few stimuli) | Range of situations (open spaces, crowds, enclosed spaces, public transport) but same underlying fear | Social situations specifically |
| Alone? | Fear persists whether alone or with others | Persists when left alone in phobic situations (no one to help) | May feel comfortable in social situations if attachment figure is present (cf. separation anxiety) |
Normal shyness or performance anxiety tends to be less severe and pervasive, and associated with little distress and functional impairment [2]. Social anxiety disorder is distinguished by:
- Intensity disproportionate to threat
- Pervasiveness (multiple social situations or avoidance of most social contexts)
- Significant distress and functional impairment
- Agoraphobia: focus of fear is panic attacks and unavailability of help/escape rather than scrutiny. Tends to persist when left alone in phobic situations.
- Social anxiety: focus is fear of scrutiny and negative evaluation. The social situation itself is feared, not the panic-related consequences.
- Panic disorder: fear concerns embarrassment due to panic attacks rather than the social situation itself
- Social anxiety: fear is specifically about being observed, criticised, or negatively evaluated in the social context
- Separation anxiety: tends to feel comfortable in social situations where attachment figure is present
- Social anxiety: anxiety occurs in social situations regardless of attachment figure presence
- Depression and delusions related to negative evaluation: may have fears of being negatively evaluated but these usually arise from mood-congruent beliefs (depressive cognitions of worthlessness) or delusional intensity (persecutory delusions), rather than the circumscribed social anxiety pattern
The theme/focus of anxiety is the key differentiating feature [2]:
| Psychiatric Disorder | Theme of Anxiety | Why It's NOT a Primary Anxiety Disorder |
|---|---|---|
| Depression | Ruminatory thoughts of guilt, worthlessness, hopelessness about past events | GAD worries are future-oriented; depressive rumination is past-oriented and mood-congruent. Note presence of somatic symptoms of depression: early morning wakening, diurnal variation in mood, suicidal thoughts (uncommon in pure GAD). Comorbidity is very common — 2/3 of GAD patients have other psychiatric diagnoses including depression [1][2] |
| OCD | Intrusive obsessional thoughts with compulsive rituals | Thoughts are ego-dystonic, bizarre/primal; compulsions are ritualistic and time-consuming (see above) |
| PTSD | Fear of traumatic memory re-experiencing | Must have exposure to traumatic event; re-experiencing symptoms (flashbacks, nightmares) and avoidance of trauma-related cues — these are not features of other anxiety disorders [2] |
| Eating disorder | Worry about gaining weight | Fear is specifically about weight/body shape, not about other concerns |
| Illness anxiety disorder (hypochondriasis) | Worry about having serious illness | GAD has multiple different worries; hypochondriacal patient worries principally about illness [2] |
| Paranoid schizophrenia | Fear of being poisoned or killed | Beliefs are of delusional intensity (fixed, not amenable to reason); other psychotic features present |
| Borderline / dependent PD | Fear of separation or abandonment | Pervasive personality pattern (not episodic); identity disturbance, affective instability |
| Avoidant PD | Fear of being rejected or inadequate | Pervasive personality pattern since adolescence; overlaps significantly with social anxiety disorder |
| ADHD (in children) | Distraction mimics anxiety-related poor concentration | Distraction in ADHD is due to external stimuli, new activities, preoccupation with enjoyable activities vs. worrying themes in anxiety [2] |
Comorbidity for GAD [1]:
- 2/3 of GAD patients have other psychiatric diagnosis
- Depression
- Other anxiety disorders (e.g. panic, social anxiety)
- Personality disorder (e.g. anankastic, paranoid, avoidant)
- Alcohol and drug abuse
GAD + Depression: A Common Trap
GAD and depression frequently coexist — this is the rule rather than the exception. When both are present, consider: (1) relative severity of each, (2) temporal sequence (which came first?), (3) content of rumination (future-oriented worry = GAD; past-oriented guilt/worthlessness = depression). In ICD-10, "mixed anxiety-depressive disorder" is used when neither is predominant and neither meets full criteria. In DSM-5, both can be diagnosed as comorbidities [2].
| Disorder | Distinguishing Feature |
|---|---|
| PTSD | Must follow traumatic event; characterised by re-experiencing (flashbacks, nightmares), avoidance of trauma cues, negative cognitions/mood, and hyperarousal. Anxiety/OCD: intrusive thoughts/worries are not related to a traumatic event |
| Acute Stress Disorder | Same symptom pattern as PTSD but lasts 3 days to 1 month following trauma (PTSD requires > 1 month) |
| Adjustment Disorder | Develops ≤3 months of a stressor; stressor can be of any severity (not necessarily traumatic); symptom pattern does not meet criteria for any specific disorder (GAD, MDD, PTSD). It is a residual category — diagnosed only when other diagnoses cannot be made [2] |
Adjustment disorder is essentially what you diagnose when someone has a disproportionate reaction to a stressor but doesn't tick the boxes for anything more specific. If they meet GAD criteria, diagnose GAD. If they meet PTSD criteria, diagnose PTSD. Adjustment disorder is the "none of the above" category.
| Disorder | Key Distinction from Anxiety Disorders |
|---|---|
| Somatic symptom disorder | Both have high levels of anxiety and somatic symptoms, but in somatic symptom disorder the focus is on distress and maladaptive response to somatic symptoms. In GAD, anxiety is pervasive over multiple aspects of life, not just bodily symptoms |
| Illness anxiety disorder (hypochondriasis) | Both have maladaptive health-related anxiety, but in hypochondriasis somatic symptoms are often minimal and the patient seeks diagnosis rather than relief of symptoms |
| Conversion disorder | Presents with neurological symptoms (weakness, numbness, seizure-like episodes) without organic cause; the core issue is symptom production rather than excessive anxiety |
Differential diagnosis for phobic disorder [1]:
- DDx for anxiety symptoms: physical disorder, substance abuse etc.
- DDx for avoidance features: personality disorder, psychosis, depression
This two-pronged approach is important: when a patient presents with a phobic pattern, you need to consider:
- What else could cause these anxiety symptoms? (medical, substance)
- What else could cause avoidance? (personality disorder — e.g., avoidant PD avoids social situations due to deep-seated feelings of inadequacy; psychosis — e.g., paranoid patient avoids going out due to persecutory delusions; depression — e.g., depressed patient avoids social situations due to anhedonia, not fear)
Differential diagnosis of panic disorder [1]:
- Physical disorders: epilepsy, thyroid disease, cardiac disease, vestibular dysfunction, phaeochromocytoma
- Substance abuse: intoxication or withdrawal
- Other anxiety disorders
| D/dx Category | Specific Conditions | How to Distinguish |
|---|---|---|
| Physical disorders | Epilepsy (TLE) | Stereotyped episodes; post-ictal confusion; EEG |
| Thyroid disease | Persistent symptoms; weight changes; TFTs | |
| Cardiac disease (arrhythmias, SVT) | ECG/Holter; may have syncope; exercise-related | |
| Vestibular dysfunction | Positional vertigo; nystagmus; Dix-Hallpike | |
| Phaeochromocytoma | Episodic attacks with severe HTN; urinary catecholamines | |
| Substance abuse | Stimulant intoxication, alcohol/BZD withdrawal | Temporal relationship to substance use; toxicology |
| Other anxiety disorders | Social phobia, specific phobia, GAD, PTSD | Panic attacks are expected/cued in these disorders (not unexpected as in panic disorder) |
| Somatoform disorders | Somatic symptom disorder | Both present with somatic complaints, but in panic disorder the fear is specifically about catastrophic consequences of the somatic symptoms (dying, going mad) rather than preoccupation with the symptoms themselves [2] |
| D/dx | Key Distinguishing Feature |
|---|---|
| Agoraphobia | Avoidance is across a range of situations but focus of fear is the same across them (fear of panic symptoms / unavailable help) vs. multiple specific fears for multiple specific stimuli in specific phobias |
| Panic disorder | Panic attacks occur unexpectedly (not tied to specific stimulus) |
| Social anxiety disorder | Fear specifically concerns scrutiny, embarrassment, critical evaluation |
| PTSD | Associated with general anxiety symptoms and re-experiencing symptoms related to trauma |
| Eating disorder | Fear concerns weight gain but not concerning specific objects/situations like choking |
| If the focus of anxiety is... | Consider... | Key differentiator from primary anxiety disorders |
|---|---|---|
| Free-floating, multiple topics | GAD | Continuous; future-oriented worry; ≥6 months |
| Unexpected panic attacks | Panic disorder | Attacks are uncued; persistent worry about attacks |
| Specific situation/object | Specific phobia | Circumscribed stimulus; recognised as irrational |
| Social scrutiny | Social anxiety disorder | Fear of negative evaluation in social contexts |
| Open spaces/crowds/confined | Agoraphobia | Fear of being unable to escape / get help |
| Separation from attachment | Separation anxiety disorder | Excessive distress on separation from attachment figure |
| Traumatic memories | PTSD / ASD | Trauma exposure; re-experiencing; avoidance of cues |
| Intrusive thoughts + rituals | OCD | Ego-dystonic obsessions; compulsions |
| Gaining weight | Eating disorder | Body image disturbance |
| Having serious illness | Illness anxiety / hypochondriasis | Principal focus on diagnosis of illness |
| Being poisoned/killed | Paranoid schizophrenia | Delusional intensity; other psychotic features |
| Guilt/worthlessness | Depression | Past-oriented rumination; mood-congruent |
| Rejection/inadequacy | Avoidant PD | Pervasive pattern since adolescence |
| Abandonment/separation | Borderline/dependent PD | Pervasive personality pattern |
| Only with substance use | Substance-induced | Temporal relationship; worst in AM (withdrawal) |
| With autonomic symptoms at rest | Medical condition | Physical signs; abnormal investigations |
D/dx for childhood anxiety: consider organic causes, e.g. hyperthyroidism, arrhythmias, neurological disease, substance-induced anxiety (alcohol, illicit drugs, caffeine) [2]
Additional childhood-specific differentials:
- Normal developmental fears — age-appropriate fears (e.g., stranger anxiety in infants, fear of the dark in preschoolers) are not anxiety disorders. Only diagnose when developmentally inappropriate, more severe and prolonged than usual, and causing significant distress + functional impairment [2]
- ADHD — both can show inattention and poor concentration, but in ADHD the distraction is from external stimuli and enjoyable activities, not from worrying themes [2]
- ASD — social avoidance is due to poor social skills and restricted interests, not fear of negative evaluation
- School refusal — may be a manifestation of separation anxiety disorder, social anxiety, specific phobia, depression, or even bullying. Identify the underlying driver.
High Yield Summary — Differential Diagnosis of Anxiety Disorders
Step 1: Exclude organic causes (thyrotoxicosis, hypoglycaemia, phaeochromocytoma, cardiac arrhythmia, PE, TLE, vestibular dysfunction) — always check TFTs and glucose at minimum.
Step 2: Exclude substance-induced anxiety (intoxication: stimulants, caffeine, cannabis; withdrawal: alcohol, BZDs; medication S/E: SSRIs early, steroids, T4).
Step 3: Exclude higher-order psychiatric disorders (psychosis → mood disorders → then anxiety).
Key differentiators between anxiety disorders: Identify the focus of fear and the pattern (continuous vs. episodic; expected vs. unexpected).
- GAD: free-floating, multiple topics, continuous, ≥6 months
- Panic disorder: unexpected panic attacks + persistent worry about attacks
- Social anxiety: fear of scrutiny/negative evaluation in social situations
- Specific phobia: circumscribed fear of specific object/situation
- Agoraphobia: fear of being unable to escape/get help (crowds, open/enclosed spaces)
- PTSD: follows trauma; re-experiencing + avoidance + hyperarousal
- OCD: ego-dystonic obsessions + ritualistic compulsions
2/3 of GAD patients have comorbid psychiatric diagnoses — depression, other anxiety disorders, personality disorders, substance use.
Adjustment disorder is a residual category — only diagnosed when no other specific disorder criteria are met.
Active Recall - Differential Diagnosis of Anxiety Disorders
References
[1] Lecture slides: GC 167. I feel very nervous Anxiety disorders.pdf (p12, p18, p27, p30) [2] Senior notes: ryanho-psych.md (Sections 8.1.1 Approach to Anxiety, 8.1.2 GAD D/dx, 8.1.3 Panic Disorder D/dx, 8.1.4 Phobic Anxiety Disorders D/dx, 8.2 PTSD D/dx, 8.3.3 Adjustment Disorder D/dx, 12.5 Childhood Anxiety Disorders D/dx)
Diagnostic Criteria for Anxiety Disorders
Diagnosis of anxiety disorders is fundamentally clinical — it rests on a careful psychiatric history, mental state examination, and the application of standardised diagnostic criteria (DSM-5-TR or ICD-11). There is no blood test or scan that "diagnoses" an anxiety disorder. Investigations exist primarily to exclude organic mimics and to assess comorbidities.
Let's walk through the diagnostic criteria for each major anxiety disorder, then the diagnostic algorithm and the role of investigations.
Before diving into individual criteria, understand that all anxiety disorder diagnostic criteria share the same logical skeleton:
- Core symptom cluster — the specific pattern of fear/anxiety/worry
- Trigger/context specificity — what triggers it (or whether it is "free-floating")
- Duration threshold — minimum time symptoms must be present (prevents diagnosing transient normal reactions)
- Severity threshold — must cause clinically significant distress or functional impairment
- Exclusion criteria — not attributable to substance/medical condition; not better explained by another mental disorder
The exclusion criteria exist because of the diagnostic hierarchy: organic → substance → psychotic → mood → anxiety. You only diagnose a primary anxiety disorder after ruling out conditions higher in the hierarchy [2].
ICD-10 vs DSM-5: A Key Philosophical Difference
In ICD-10, GAD is essentially a diagnosis of exclusion — it is NOT diagnosed if criteria for panic disorder, phobic anxiety, or OCD are met. In DSM-5, GAD can be diagnosed comorbidly alongside other anxiety disorders because DSM-5 emphasises excessive worry as a core feature with a specific 6-month duration [2]. This difference is commonly tested.
1. Generalised Anxiety Disorder (GAD)
A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). [1]
Why "more days than not for ≥6 months"? This duration threshold distinguishes GAD from normal transient worry. If it only lasted a few weeks after a stressor, you'd consider adjustment disorder or normal stress reaction instead.
B. The person finds it difficult to control the worry. [1]
This criterion captures the essence of pathological worry — the patient recognises their worry is excessive but cannot stop it. This is unlike normal worry which can be "put aside."
C. Associated with 3 or more of the following 6 symptoms (≥1 in children), with at least some symptoms present for more days than not for the past 6 months [1]:
- Restlessness or feeling keyed up or on edge — sustained locus coeruleus activation → chronic heightened arousal
- Being easily fatigued — chronic hyperarousal depletes energy reserves; sustained cortisol → metabolic effects
- Difficulty concentrating or mind going blank — prefrontal resources hijacked by worry circuit
- Irritability — chronic amygdala activation → ↓threshold for emotional reactivity
- Muscle tension — sustained sympathetic-mediated skeletal muscle contraction
- Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep) — failure to suppress amygdala/LC at night
Mnemonic: "R-E-D-I-M-S" — Restlessness, Easy fatigue, Difficulty concentrating, Irritability, Muscle tension, Sleep disturbance
D. Causes clinically significant distress and functional impairment. [1]
E. Not due to the direct physiological effects of substance or general medical conditions. [1]
F. Not explained by another mental disorder. [1]
| Feature | ICD-10 | DSM-5 |
|---|---|---|
| Core feature | Primary symptoms of anxiety most days, usually several months | Excessive anxiety and worry, ≥6 months |
| Symptom domains | (a) Apprehension, (b) Motor tension, (c) Autonomic overactivity | ≥3 of 6 symptoms (REDIMS) |
| Children | Frequent need for reassurance and recurrent somatic complaints | ≥1 of 6 symptoms |
| Co-diagnosis | NOT diagnosed if criteria for panic, phobic anxiety, or OCD are met (exclusionary) | CAN be diagnosed alongside other anxiety disorders |
ICD-11 (6B00) requires: a period of at least six months with prominent tension, worry and feelings of apprehension, about everyday events and problems, with at least four symptoms from: autonomic arousal symptoms, symptoms concerning chest and abdomen, symptoms concerning brain and mind, general symptoms [4]
Additional ICD-10/11 Features for GAD
The ICD approach groups symptoms differently — emphasising autonomic arousal, chest/abdominal symptoms, brain/mind symptoms, and general symptoms. The DSM approach groups them as the 6 REDIMS items. Both capture the same clinical picture from slightly different angles.
- Early morning wakening is NOT a feature of GAD → strongly suggests depressive disorder [2]
- Transient appearance of other symptoms (especially depression) does NOT rule out GAD as main diagnosis, but the sufferer must not meet full criteria for depressive episode, phobic anxiety, panic disorder, or OCD (ICD-10 approach) [2]
- In children: frequent need for reassurance and recurrent somatic complaints may be prominent [2]
- Course: usually gradual onset; full syndrome emerges after prolonged subsyndromal symptoms [2]
2. Panic Disorder
A. Recurrent unexpected panic attacks — an abrupt surge of intense fear/discomfort that reaches a peak within minutes, during which ≥4 of the following symptoms occur [1]:
| # | Symptom | Pathophysiological Basis |
|---|---|---|
| 1 | Palpitations, pounding heart or ↑HR | β₁ sympathetic activation of SA node |
| 2 | Sweating | Sympathetic cholinergic eccrine gland activation |
| 3 | Trembling or shaking | β₂-adrenergic skeletal muscle activation |
| 4 | Sensations of SOB or smothering | Sympathetic activation of respiratory drive |
| 5 | Feelings of choking | Pharyngeal muscle tension; hyperventilation |
| 6 | Chest pain or discomfort | Chest wall tension; hyperventilation-related vasospasm |
| 7 | Nausea or abdominal distress | Sympathetic → ↓GI motility; vagal stimulation |
| 8 | Feeling dizzy, unsteady, light-headed, or faint | Hyperventilation → ↓pCO₂ → cerebral vasoconstriction |
| 9 | Chills or heat sensations | Sympathetic vasomotor instability |
| 10 | Paraesthesias (numbness or tingling) | Respiratory alkalosis → ↓ionised Ca²⁺ → neuronal hyperexcitability |
| 11 | Derealisation or depersonalisation | Amygdala-cortical disconnect during extreme fear response |
| 12 | Fear of losing control or "going crazy" | Catastrophic misinterpretation of somatic symptoms |
| 13 | Fear of dying | Catastrophic misinterpretation (e.g., "this must be a heart attack") |
Why ≥4 symptoms? Because < 4 symptoms ("limited-symptom attacks") are common in the general population and are not sufficiently specific for panic disorder. The threshold of 4 increases diagnostic specificity.
B. At least one of the attacks has been followed by 1 month of one or both of the following [1]:
- Persistent concern about having additional attacks or their consequences ("anticipatory anxiety")
- A significant maladaptive change in behaviour related to the attacks (e.g., avoidance of exercise, agoraphobic patterns)
Criterion B is crucial — it's not enough to just have panic attacks. The attacks must lead to persistent worry or behavioural change. Otherwise, isolated panic attacks (which are common in the general population) would be over-diagnosed.
C. Not due to direct physiological effects of a substance or a general medical condition. [1]
D. Not better accounted for by another mental disorder. [1]
| ICD-10 | DSM-5 |
|---|---|
| Several severe attacks of autonomic anxiety within ~1 month | Recurrent unexpected panic attacks with ≥4/13 symptoms |
| (a) In circumstances where there is no objective danger | Unexpected = no obvious cue/trigger |
| (b) Not confined to known or predictable situations | Same concept — not cued by specific stimuli |
| (c) Comparable freedom from anxiety between attacks (anticipatory anxiety common) | ≥1 month of persistent concern or behavioural change |
| NOT diagnosed when secondary to phobic or depressive disorders | Not better explained by another mental disorder |
3. Specific Phobia
A. Marked fear or anxiety about a specific object or situation. [1]
B. The phobic object or situation almost always provokes immediate fear or anxiety. [1]
"Almost always" = the response is consistent and reliable — not occasional or variable. This distinguishes phobia from incidental anxiety.
C. The phobic object or situation is actively avoided or endured with intense fear or anxiety. [1]
D. The fear or anxiety is out of proportion to the actual danger posed by the specific object or situation and to the sociocultural context. [1]
"Sociocultural context" matters — fear of snakes is reasonable in rural Australia but not in urban Hong Kong. The fear must exceed what is culturally normative.
E. The fear, anxiety, or avoidance is persistent, typically lasting for 6 months or more. [1]
F. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. [1]
G. The disturbance is not better explained by other mental disorder. [1]
Specifiers: (1) animal, (2) natural environment, (3) blood-injection-injury, (4) situational, (5) other [2]
ICD-10 requires that:
- (a) Psychological or autonomic symptoms are primary manifestations of anxiety, not secondary to other symptoms (e.g., delusions, obsessions)
- (b) Anxiety is restricted to the presence of the particular phobic object/situation
- (c) The phobic situation is avoided whenever possible
4. Social Anxiety Disorder (Social Phobia)
A. Marked fear or anxiety about one or more social situations in which the individual is exposed to possible scrutiny by others. [1]
Examples: social interactions (conversations, meeting unfamiliar people), being observed (eating, drinking), performing (giving a speech).
B. The individual fears that he or she will act in a way or show anxiety symptoms that will be negatively evaluated. [1]
This is the core cognitive distortion — fear of negative evaluation (humiliation, embarrassment, rejection, offending others).
C. The social situations almost always provoke fear or anxiety. [1]
D. The social situations are avoided or endured with intense fear or anxiety. [1]
E. The fear or anxiety is out of proportion to the actual threat posed by the social situations and to the sociocultural context. [1]
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6 months or more. [1]
G. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. [1]
H. The fear, anxiety, or avoidance is not attributable to the physiological effects of a substance or another medical condition. [1]
I. The fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder. [1]
J. If another medical condition (e.g., PD, obesity, disfigurement from burns/injury) is present, the fear, anxiety, or avoidance is clearly unrelated or is excessive. [1]
Criterion J is often forgotten — a patient with Parkinson's tremor may reasonably be self-conscious. Only diagnose social anxiety disorder if the fear is clearly excessive relative to the medical condition.
Specifier: "performance only" — if fear is restricted to speaking or performing in public [1]
- Requires primary manifestation of anxiety (not secondary to delusions/obsessions)
- Anxiety must be restricted to or predominate in particular social situations
- Diagnostic precedence given to agoraphobia if difficult to distinguish [2]
DSM-5 Criteria [1][2]
A. Marked fear or anxiety about two (or more) of the following five situations [1]:
- Using public transportation (buses, trains, ships, planes)
- Being in open spaces (parking lots, marketplaces, bridges)
- Being in enclosed places (shops, theatres, cinemas)
- Standing in line or being in a crowd
- Being outside of the home alone
B. The individual fears or avoids these situations because of thoughts that escape might be difficult or help might not be available in the event of developing panic-like symptoms or other incapacitating or embarrassing symptoms. [1]
This is the core cognitive distortion in agoraphobia — it's NOT a fear of the place itself, but a fear of what might happen (panic, incapacitation) and the inability to escape or get help. This is why "agoraphobia" (Greek: "agora" = marketplace + "phobos" = fear → "fear of the marketplace") is slightly misleading — it's not really fear of open spaces, but fear of being unable to escape/get help in those spaces.
C. The agoraphobic situations almost always provoke fear or anxiety. [1]
D. The agoraphobic situations are actively avoided, require the presence of a companion, or are endured with intense fear or anxiety. [1]
E. The fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations and to the sociocultural context. [1]
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6 months or more. [1]
G. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. [1]
H. If another medical condition (e.g., IBD, PD) is present, the fear, anxiety, or avoidance is clearly excessive. [1]
I. Not better explained by other mental disorder. [1]
Key Change in DSM-5
In DSM-IV, agoraphobia could only be diagnosed as a specifier of panic disorder ("panic disorder with agoraphobia"). In DSM-5, agoraphobia is a separate diagnosis that can exist independently of panic disorder. Both can be coded if both criteria sets are met. In ICD-10, agoraphobia with panic disorder is still coded as a single entity.
DSM-5 Criteria (Abbreviated) [2]
- A. Exposure to actual or threatened death, serious injury, or sexual violence (directly, witnessing, learning about, or repeated exposure)
- B. ≥1 intrusion symptoms: recurrent intrusive memories, distressing dreams, dissociative reactions (flashbacks), psychological/physiological distress at trauma cues
- C. Persistent avoidance of stimuli associated with the traumatic event (≥1 of: avoidance of distressing memories/thoughts/feelings; avoidance of external reminders)
- D. Negative alterations in cognitions and mood associated with the event (≥2 of: inability to remember, negative beliefs, distorted cognitions, negative emotional state, diminished interest, detachment, inability to experience positive emotions)
- E. Marked alterations in arousal and reactivity (≥2 of: irritable behaviour, reckless behaviour, hypervigilance, exaggerated startle, concentration problems, sleep disturbance)
- F. Lasting > 1 month in duration (< 1 month = Acute Stress Disorder)
- G. Clinically significant distress or functional impairment
- H. Not attributable to substance or medical condition
- Stressor: identifiable stressor of any severity (not necessarily traumatic), onset ≤3 months of stressor [2]
- Symptoms: emotional/behavioural symptoms out of proportion to stressor
- Residual category: should NOT be diagnosed if criteria for another specific disorder (GAD, MDD, PTSD) are met [2]
- Subtypes: with depressed mood, with anxiety, with mixed anxiety and depressed mood, with disturbance of conduct, with mixed disturbance of emotions and conduct, unspecified
| Disorder | Core Feature | Trigger | Duration | Key Exclusions |
|---|---|---|---|---|
| GAD | Excessive worry about multiple events/activities; ≥3/6 REDIMS | Free-floating (not situation-specific) | ≥6 months | Substance, medical, other mental disorder |
| Panic Disorder | Recurrent unexpected panic attacks (≥4/13 symptoms) + persistent concern/behavioural change | Unexpected (no cue) | ≥1 month of concern after attack | Substance, medical, other mental disorder |
| Specific Phobia | Marked fear of specific object/situation; almost always provokes fear | Specific stimulus | ≥6 months | Other mental disorder |
| Social Anxiety | Marked fear of social situations with possible scrutiny; fears negative evaluation | Social situations | ≥6 months | Substance, medical, other mental disorder |
| Agoraphobia | Fear/anxiety about ≥2/5 situations; fears escape difficulty/help unavailability | Public transport, open/enclosed spaces, crowds, alone outside | ≥6 months | Medical condition (if present, must be clearly excessive) |
| PTSD | Intrusion + avoidance + negative cognitions/mood + hyperarousal | Following traumatic event | > 1 month | Substance, medical (ASD if 3d–1mo) |
| Adjustment Disorder | Emotional/behavioural symptoms out of proportion to stressor | Identifiable stressor (any severity) | ≤3 months onset from stressor | Residual — NOT diagnosed if other criteria met |
The clinical approach to diagnosing anxiety disorders follows a systematic, hierarchical process. Here is the comprehensive diagnostic algorithm:
Investigation Modalities
Key Principle
Anxiety disorders are diagnosed clinically through history and mental state examination. Investigations serve to: (1) exclude organic mimics, (2) establish a baseline before pharmacotherapy, and (3) assess comorbidities. There is no diagnostic blood test or imaging study for any anxiety disorder.
These are the essential investigations when anxiety is the presenting complaint, particularly when clinical features suggest a possible organic aetiology (e.g., new onset in middle age, atypical features, lack of psychological triggers, prominent autonomic symptoms at rest):
| Investigation | What It Excludes | Key Findings That Suggest Organic Cause | Interpretation |
|---|---|---|---|
| Thyroid function tests (TFTs) | Thyroid disease [1] | ↓TSH, ↑fT₃/fT₄ (thyrotoxicosis) | Thyrotoxicosis causes ↑sympathetic sensitivity → autonomic symptoms mimicking anxiety. If TFTs abnormal → treat thyroid disease first and reassess anxiety |
| Fasting glucose / HbA1c | Hypoglycaemia, diabetes | ↓Glucose during symptomatic episodes | Hypoglycaemia triggers counter-regulatory catecholamine surge → sweating, tremor, palpitations. If episodic and temporally related to fasting → endocrine workup |
| Serum calcium | Hyperparathyroidism | ↑Ca²⁺ | Hypercalcaemia → neuropsychiatric symptoms including anxiety, confusion, depression |
| FBC | Anaemia, infection | ↓Hb (tachycardia, fatigue), ↑WCC (infection) | Anaemia causes compensatory tachycardia → perceived as palpitations/anxiety |
| U&E, renal function | Electrolyte disturbance | Various electrolyte abnormalities | Baseline before starting medications (e.g., SSRIs can cause hyponatraemia) |
| LFTs | Hepatic disease; alcohol use | ↑GGT (alcohol), ↑AST/ALT | Elevated GGT may suggest covert alcohol use (self-medication); baseline before drugs |
| ECG | Cardiac disease (arrhythmia, SVT) [1] | Tachyarrhythmia (SVT, AF), prolonged QTc | Arrhythmias cause episodic palpitations mimicking panic attacks. Also needed as baseline before starting SSRIs/TCAs (QTc prolongation risk) |
| 24-hour Holter monitor | Paroxysmal arrhythmias | Captured arrhythmia episodes | If ECG is normal but episodes are paroxysmal and suggestive |
| 24h urinary catecholamines / plasma metanephrines | Phaeochromocytoma [1] | ↑Urinary catecholamines, ↑plasma metanephrines | Phaeochromocytoma causes episodic catecholamine surges → severe "panic-like" attacks with marked hypertension |
| CXR | Cardiac/pulmonary disease | Cardiomegaly (HF), hyperinflation (COPD), infiltrates | Dyspnoea from cardiac/pulmonary disease → anxiety |
| Spirometry | COPD, asthma | Obstructive pattern (↓FEV₁/FVC) | Air hunger from obstructive lung disease can trigger or mimic anxiety |
| EEG | Epilepsy (especially TLE) [1] | Epileptiform discharges, temporal lobe abnormalities | Temporal lobe epilepsy can cause ictal fear, déjà vu, automatisms that mimic panic |
| CTPA / D-dimer | Pulmonary embolism | Filling defects on CTPA; ↑D-dimer | If clinical suspicion (pleuritic pain, haemoptysis, risk factors) |
| CT/MRI brain | Structural brain pathology | Mass lesions, temporal lobe pathology | Only if focal neurological signs, late-onset atypical anxiety, or cognitive decline suggestive of dementia |
| Investigation | Purpose | Key Findings |
|---|---|---|
| Urine drug screen | Detect stimulant/illicit drug use | Positive for amphetamines, cocaine, cannabis, opioids |
| Blood alcohol level | Acute intoxication/withdrawal | Elevated BAL; or clinical features of withdrawal with low/zero BAL |
| Urine toxicology | Comprehensive substance screen | Benzodiazepines (if not prescribed), other substances |
| Medication review | Iatrogenic anxiety | Recently started SSRI (first 2 weeks), corticosteroids, sympathomimetics, T₄, anticholinergics, antipsychotics (akathisia) |
These are not diagnostic but help quantify severity, track treatment response, and screen for comorbidities:
| Scale | What It Measures | Key Details |
|---|---|---|
| GAD-7 (Generalised Anxiety Disorder 7-item) | Anxiety symptom severity | 7 items scored 0–3; total 0–21. ≥5 mild, ≥10 moderate, ≥15 severe. Most widely used in primary care and research |
| PHQ-9 (Patient Health Questionnaire 9) | Depression severity | Essential comorbidity screen — GAD + MDD co-occur in > 50% |
| Beck Anxiety Inventory (BAI) | Anxiety symptoms (somatic focus) | 21 items; distinguishes anxiety from depression better than some tools |
| Hamilton Anxiety Rating Scale (HAM-A) | Anxiety severity | Clinician-rated; 14 items; commonly used in clinical trials |
| Panic Disorder Severity Scale (PDSS) | Panic disorder severity | 7 items assessing panic frequency, distress, avoidance, anticipatory anxiety |
| Liebowitz Social Anxiety Scale (LSAS) | Social anxiety severity | 24 items assessing fear and avoidance in social/performance situations |
| SPIN (Social Phobia Inventory) | Social anxiety screening | 17 items; briefer than LSAS |
| PCL-5 (PTSD Checklist) | PTSD symptoms | 20 items mapping to DSM-5 PTSD criteria |
| Y-BOCS (Yale-Brown OCD Scale) | OCD severity | 10 items; gold standard for OCD severity assessment |
| AUDIT / CAGE | Alcohol use | Screen for comorbid alcohol use disorder (self-medication) |
Before starting medications (especially SSRIs, SNRIs, TCAs, or pregabalin), the following baseline investigations are recommended:
| Investigation | Reason |
|---|---|
| ECG | SSRIs and TCAs can prolong QTc → risk of torsades de pointes. Obtain baseline QTc. TCAs in particular require ECG monitoring |
| U&E | SSRIs can cause SIADH → hyponatraemia (especially in elderly). Baseline sodium important |
| LFTs | Hepatic metabolism of most psychotropics; baseline before hepatotoxic drugs |
| FBC | Baseline for monitoring (some drugs cause blood dyscrasias rarely) |
| TFTs | Exclude thyroid disease; also baseline if lithium is being considered (e.g., augmentation in refractory cases) |
| Weight, BMI, BP | Some medications (e.g., mirtazapine, pregabalin) cause weight gain; SNRIs can raise BP |
| Pregnancy test | In women of childbearing age — teratogenicity considerations (e.g., paroxetine is category D) |
The diagnostic process in practice involves:
1. Comprehensive psychiatric assessment:
- History of presenting complaint: onset, duration, triggers, content of worry/fear, avoidance patterns, functional impact
- Key questions to ask:
- "What do you worry about?" (GAD = multiple topics; social anxiety = scrutiny; OCD = intrusive thoughts)
- "Does the anxiety come on suddenly or is it always there?" (Panic = sudden, episodic; GAD = continuous)
- "Are there specific situations that trigger it?" (Phobic disorders = yes; GAD = no)
- "Do you avoid any situations because of the anxiety?" (Avoidance = phobic disorders, PTSD)
- "Have you had any traumatic experiences?" (PTSD screening)
- "Do you have any repetitive thoughts you can't get rid of, or rituals you feel compelled to do?" (OCD screening)
- Past psychiatric history: previous episodes, treatments tried, response
- Family history: anxiety, depression, bipolar, substance use
- Substance use history: alcohol, caffeine, illicit drugs, over-the-counter medications
- Medical history: thyroid disease, cardiac conditions, respiratory conditions
- Medication history: recent changes, new medications
2. Mental state examination (MSE):
- Appearance/Behaviour: restless, fidgeting, tremor, sweating, tense posture
- Speech: may be rapid, pressured (if anxious)
- Mood: "anxious", "nervous", "worried"
- Affect: anxious, apprehensive, fearful
- Thought content: worries (content helps differentiate disorder), catastrophic cognitions, obsessions
- Thought form: usually normal; may be circumstantial if overly detailed about worries
- Perception: usually normal (no hallucinations in primary anxiety disorders — if present, consider psychosis)
- Cognition: may have difficulty concentrating (but no true cognitive impairment — if present, consider dementia presenting with anxiety)
- Insight: usually preserved (patients typically recognise their anxiety is excessive)
- Risk: suicidal ideation (especially with comorbid depression), self-harm, substance use
3. Targeted investigations (as above — to exclude organic causes)
4. Apply diagnostic criteria (DSM-5 or ICD-11)
5. Screen for comorbidities (depression, substance use, personality disorders)
Must-Know Clinical Pitfall
In children: anxiety and fears can be developmentally appropriate. Diagnose an anxiety disorder only when developmentally inappropriate (more severe and prolonged than usual) and causes significant distress + functional impairment [2]. Also, consider organic causes: hyperthyroidism, arrhythmias, neurological disease, substance-induced anxiety (alcohol, illicit drugs, caffeine) [2].
When evaluating anxiety, certain history features should raise your index of suspicion for organic or secondary causes:
- Vague, inconsistent history mixed with normal physical sensation and abnormal checking behaviour → consider somatoform/somatic symptom disorder [2]
- Symptoms that don't fit known disease patterns or anatomical confines → consider functional neurological disorder
- Persistent anxiety and concern despite repeated help-seeking, reassurance, negative investigations, and treatment → consider illness anxiety disorder (hypochondriasis) [2]
- Late onset (middle age or elderly) without clear psychological trigger → think organic cause or dementia (BPSD)
- Prominent autonomic symptoms at rest without psychological component → think thyrotoxicosis, phaeochromocytoma
- Morning-predominant anxiety → think substance withdrawal (especially alcohol, benzodiazepines) [2]
High Yield Summary — Diagnostic Criteria and Investigation
All anxiety disorders share: core symptom cluster + trigger specificity + duration threshold (usually ≥6 months except panic disorder ≥1 month, PTSD > 1 month, adjustment disorder onset ≤3 months) + significant distress/impairment + exclusion of substance/medical/other mental disorder.
GAD criteria (REDIMS): Excessive worry ≥6 months + ≥3 of Restlessness, Easy fatigue, Difficulty concentrating, Irritability, Muscle tension, Sleep disturbance.
Panic disorder: Recurrent UNEXPECTED panic attacks (≥4/13 symptoms, peak in minutes) + ≥1 month persistent concern or behavioural change.
Specific phobia: Marked fear of specific stimulus; almost always provokes fear; out of proportion; ≥6 months; distress/impairment.
Social anxiety: Fear of social scrutiny/negative evaluation; ≥6 months; distress/impairment. Specifier: "performance only."
Agoraphobia: Fear of ≥2/5 situations (public transport, open spaces, enclosed places, crowds, alone outside); fears inability to escape/get help; ≥6 months.
ICD-10 vs DSM-5: ICD-10 treats GAD as diagnosis of exclusion; DSM-5 allows comorbid diagnosis.
Essential investigations: TFTs, glucose, ECG (also baseline for SSRIs/TCAs), Ca²⁺, FBC, U&E, LFTs. Consider 24h urinary catecholamines (phaeochromocytoma), EEG (TLE), urine drug screen.
Screening tools: GAD-7 (anxiety), PHQ-9 (depression comorbidity), BAI, HAM-A.
Diagnosis is clinical — investigations exclude organic mimics and establish treatment baselines.
Active Recall - Diagnostic Criteria and Investigations for Anxiety Disorders
[1] Lecture slides: GC 167. I feel very nervous Anxiety disorders.pdf (p12, p16, p18, p21, p23, p25, p27, p29) [2] Senior notes: ryanho-psych.md (Sections 8.1.1 Approach to Anxiety, 8.1.2 GAD diagnostic criteria and D/dx, 8.1.3 Panic Disorder diagnostic criteria, 8.1.4 Phobic Anxiety Disorders diagnostic criteria, 8.2 PTSD diagnostic criteria, 8.3.3 Adjustment Disorder, 12.5 Childhood Anxiety Disorders) [4] Lecture slides: GC 171. Stress-related disorders and obsessive-compulsive disorder_rev.pdf (p7, p15)
Management of Anxiety Disorders
The management of anxiety disorders follows a structured, evidence-based approach that integrates psychoeducation, psychological therapy, and pharmacotherapy in a stepped-care model. The overarching principle is that treatment should be proportionate to severity — start simple, escalate if needed.
Before we dive into specifics, here are the key principles that guide treatment decisions:
1. Address the hierarchy first [2]:
- If harmful or dependent alcohol/substance use is present → treat substance use first (often leads to large improvement in anxiety or depressive symptoms)
- If anxiety symptoms are secondary to depression → treat depression first
- If depressive symptoms are secondary to anxiety disorder → treat anxiety first
- If unclear which is primary → ask the patient their preference
This makes sense from first principles: if alcohol withdrawal is driving the anxiety, no amount of CBT will fix it. Similarly, if depression is generating the anxiety, treating the depression will resolve the anxiety without needing to target it specifically.
2. Stepped-care approach [2]:
- Step 1: Identification, assessment, psychoeducation, active monitoring
- Step 2: Low-intensity psychological interventions (self-help, group psychoeducation)
- Step 3: High-intensity psychological interventions (CBT, applied relaxation) OR pharmacotherapy
- Step 4: Specialist treatment — complex drug and psychological regimens with multidisciplinary input
Initiate treatment at Step 3 if the patient presents with more severe symptomatology and/or significant functional impairment [2]
3. Psychotherapy is generally more effective than pharmacotherapy and is usually first-line [2]
4. When pharmacotherapy is used:
- Short-term: BZDs should NOT be used beyond 2–4 weeks [2]
- Long-term: SSRIs as first-line, with SNRIs/pregabalin as alternatives [2]
- Continue effective treatment for at least 6 months to prevent relapse [2]
Consider referral to secondary care if: risk of self-harm or suicide, marked self-neglect, non-response to at least two treatments, significant comorbidity (e.g., substance use, physical health problems) [2]
Treatment Modalities
I. Supportive Measures
Treatment of anxiety disorders begins with supportive measures [1]:
- Psychoeducation about the nature of anxiety: explain that anxiety is a normal survival response that has become overactive, not a sign of weakness or "going crazy"
- Explain the fight-or-flight mechanism in simple terms — "your body's alarm system is too sensitive"
- Explain that somatic symptoms (palpitations, dizziness, breathlessness) are produced by adrenaline and are not dangerous, even though they feel frightening
- Explain the role of avoidance in maintaining anxiety — "avoidance makes the anxiety worse in the long run because you never learn that the feared outcome doesn't happen"
- After organic causes have been excluded, provide confident reassurance that there is no underlying physical disease
- This is particularly important for panic disorder patients who often believe they are having heart attacks or dying
- Reassurance alone is often insufficient for established anxiety disorders but is a necessary foundation
II. Psychological Treatment
Psychological treatment is the cornerstone of anxiety disorder management [1][2]. Psychotherapy is more effective than pharmacological therapy, usually as first-line [2].
- Includes written and electronic materials with information about the disorder, practical exercises based on CBT principles [2]
- Can be pure self-help (minimal therapist input) or guided self-help (supported by a trained practitioner) [2]
- Examples: bibliotherapy (self-help books), computerised CBT programmes, smartphone apps
- Appropriate for mild-moderate anxiety with minimal functional impairment
CBT is the gold standard psychological treatment for anxiety disorders. Let's understand why from first principles.
Theoretical basis: Anxiety disorders are maintained by a cycle of:
- Cognitive distortions (catastrophising, overestimating threat, intolerance of uncertainty)
- Avoidance behaviour (prevents disconfirmation of feared outcomes → fear persists)
- Physiological arousal (autonomic activation reinforces belief that something is wrong)
CBT is designed to help control worrying thoughts [2]. GAD patients tend to have a series of cognitive patterns, e.g., overestimate and catastrophise negative events and show limited confidence in problem-solving [2].
CBT components for anxiety disorders:
| Component | What It Involves | Why It Works |
|---|---|---|
| Psychoeducation | Teaching patient about anxiety mechanisms, fight-or-flight, cognitive distortions | Understanding reduces fear of symptoms; normalises experience |
| Cognitive restructuring | Identifying and challenging maladaptive thoughts (e.g., "palpitations = heart attack") | Replaces catastrophic interpretations with realistic appraisals |
| Exposure therapy | Systematic, repeated confrontation of feared stimulus/situation | Extinction of conditioned fear response; inhibitory learning ("nothing bad happens") |
| Behavioural experiments | Testing feared predictions in real life (e.g., "if I give a speech, will people laugh?") | Provides direct evidence against catastrophic beliefs |
| Relaxation training | Progressive muscle relaxation, diaphragmatic breathing | ↓Sympathetic arousal; gives patient tools to manage acute anxiety |
| Relapse prevention | Identifying early warning signs; developing coping plans | Prevents return of symptoms after treatment ends |
Efficacy: superior to placebo and other psychological treatments [2]. As effective as antidepressants in treatment of panic disorders; combination treatment may give better response in early stages but long-term results are uncertain [2].
For Phobic Disorders [1]:
Psychotherapy for phobic disorders [1]:
- Targeting the avoidance (hierarchy list)
- Exposure techniques:
- Graduated, repeated, prolonged, clear tasks
- Real-life, imaginal exposure
- Home-based, relative support
- Relaxation exercise
For social phobia specifically [1]:
- Social skill training
- Cognitive treatment for fear of negative evaluation from others
Specific phobia [2]:
- Exposure-based psychotherapy as mainstay
- Method: repeated, systematic confrontation of feared stimulus → ↓fear by extinction and inhibitory learning
- Usually graded, i.e., progressively up the hierarchy from least to most feared/avoided based on patient's subjective fears
- Types: in vivo (more effective), imaginal, VR (virtual reality)
- Efficacy: very effective, 70–85% shows significant improvement, multi-session > single session [2]
Why does exposure work? The fear response is a conditioned response (classical conditioning). Repeated exposure without the feared outcome occurring leads to extinction — the conditioned stimulus (e.g., spider) is no longer paired with the unconditioned stimulus (actual harm) → the fear response gradually diminishes. Additionally, inhibitory learning occurs: a new "safe" memory is formed that competes with the original "danger" memory.
For PTSD [2]:
- Trauma-focused CBT as first-line:
- Psychoeducation: patients are educated on stressful reactions and their cognitive underpinnings
- Cognitive restructuring: address maladaptive or unrealistic appraisals by patient towards trauma
- Exposure therapy: assist patient in confronting feared memories and situations; allow emotional processing
- Eye movement desensitisation and reprocessing (EMDR):
- Patient imagines a scene from trauma, focusing on accompanying cognition and arousal, while the therapist moves two fingers across the patient's visual field and instructs the patient to track fingers
- Sequence repeated until anxiety decreases, with patient instructed to generate a more adaptive thought
- Efficacy: most studies show it is efficacious in PTSD, superior to other less specific psychotherapy [2]
Critical Incident Stress Debriefing — Does NOT Work
Critical incident stress debriefing (CISD) involves going through traumatic events together with the victim. Although widely used, it has NOT been shown to be helpful in decreasing psychological distress [2]. This is frequently tested — CISD is NOT recommended for preventing PTSD.
- A structured form of relaxation training specifically designed to apply learned relaxation skills to anxiety-provoking situations [2]
- Involves progressive muscle relaxation, then learning to apply relaxation rapidly in real-world anxiety situations
- Evidence supports its use particularly for GAD, alongside CBT [2]
| Modality | Role |
|---|---|
| Mindfulness-based therapy | Used alongside CBT [4]; focuses on becoming aware of thoughts/feelings and accepting them rather than reacting |
| Interpersonal therapy | Focus on relationship difficulties contributing to anxiety |
| Psychodynamic therapy | Explores unconscious conflicts; less evidence base than CBT for anxiety |
| Counselling / problem-solving | Brief, for minor difficulties and stressful events; assists patients in finding solutions [2] |
III. Pharmacological Treatment
Medications used in anxiety disorders [1]:
General treatment approaches include pharmacotherapy with antidepressants, anxiolytics, antipsychotics, mood stabilisers [4].
A. Antidepressants — First-Line Pharmacotherapy
The term "antidepressant" is misleading — these drugs are equally effective for anxiety disorders. They work by modulating the serotonin and noradrenaline systems that are dysregulated in anxiety (as discussed in the neurocircuitry section).
SSRIs: Paroxetine, Citalopram, Escitalopram, Fluoxetine, Sertraline, Fluvoxamine [1]
| Feature | Detail |
|---|---|
| Mechanism | Block serotonin transporter (SERT) → ↑synaptic 5-HT → enhanced serotonergic modulation of amygdala and CSTC circuits → anxiolysis |
| Onset | 2–4 weeks for anxiolytic effect (initial 1–2 weeks may see paradoxical ↑anxiety due to stimulation of anxiogenic 5HT2C receptors before adaptive downregulation) |
| Starting | Start low, go slow — most result in ↑anxiety symptoms (apprehension, sleeplessness, palpitations) initially → dose should be increased very slowly [2] |
| Duration | Continue for ≥6 months after symptom control to prevent relapse [2] |
| Indications | First-line for GAD, panic disorder, social anxiety disorder, specific phobia (if severe), PTSD, OCD |
| Side effects | GI upset (nausea, diarrhoea), sexual dysfunction, insomnia/somnolence, headache, initial anxiety exacerbation, hyponatraemia (SIADH, especially elderly), QTc prolongation (citalopram, escitalopram), discontinuation syndrome (especially paroxetine — short half-life) |
| Contraindications | Concurrent MAOIs (serotonin syndrome risk), caution in mania/hypomania history, pregnancy (paroxetine is category D — cardiac malformations) |
Why do SSRIs initially worsen anxiety? When you first block SERT, serotonin floods ALL 5-HT receptors — including the 5HT2C receptor, which is anxiogenic. Over 2–4 weeks, the anxiogenic receptors downregulate, and the net effect becomes anxiolytic. This is why you "start low, go slow" and warn patients that the first 2 weeks may be uncomfortable.
SSRI Choice in Anxiety Disorders
There is no strong evidence that one SSRI is superior to another for anxiety. Choice is usually based on side-effect profile, drug interactions, and patient factors. Sertraline and escitalopram are often preferred due to favourable interaction profiles. Paroxetine is effective but has the highest discontinuation syndrome risk. Fluoxetine has the longest half-life (less discontinuation syndrome but longer washout if switching).
SNRIs: Venlafaxine, Duloxetine [1]
| Feature | Detail |
|---|---|
| Mechanism | Block both SERT and noradrenaline transporter (NET) → ↑synaptic 5-HT AND NA → dual modulation. Long-term: downregulation of adrenergic receptors → anxiolysis |
| Indications | GAD (first-line alternative to SSRIs), panic disorder, social anxiety disorder, PTSD |
| Side effects | Similar to SSRIs + ↑BP (NA effect — monitor BP), more prominent discontinuation syndrome (especially venlafaxine — very short half-life) |
| Contraindications | Uncontrolled hypertension (NA-mediated BP elevation); concurrent MAOIs |
Why add noradrenaline blockade? Because noradrenaline drives the autonomic/somatic symptoms of anxiety. By downregulating adrenergic receptors long-term, SNRIs address both the cognitive (5-HT) and somatic (NA) dimensions of anxiety.
TCAs: Imipramine: panic disorder; Clomipramine: OCD [1]
| Feature | Detail |
|---|---|
| Mechanism | Non-selective reuptake inhibition of 5-HT and NA + variable anticholinergic, antihistaminic, and α-adrenergic blocking effects |
| Indications | Imipramine — specifically for panic disorder; Clomipramine — specifically for OCD (most serotonergic TCA) [1] |
| Side effects | Anticholinergic (dry mouth, constipation, urinary retention, blurred vision), sedation, weight gain, postural hypotension, QTc prolongation (cardiac toxicity — dangerous in overdose), lowered seizure threshold |
| Contraindications | Recent MI, arrhythmias, heart block; caution in suicidal patients (lethal in overdose — as few as 10 days' supply can be fatal); concurrent MAOIs; narrow-angle glaucoma; prostatic hypertrophy |
TCAs are not first-line due to their side-effect profile and lethality in overdose. However, they remain important second-line options, particularly imipramine for panic and clomipramine for OCD.
MAOIs: Phenelzine: phobia [1] Reversed Inhibitor of MAO-A (RIMA): Moclobemide: phobia [1]
| Feature | Detail |
|---|---|
| Mechanism | Inhibit monoamine oxidase → ↓breakdown of 5-HT, NA, DA → ↑synaptic monoamines |
| Phenelzine (irreversible, non-selective) | Effective for social phobia and other phobias; requires strict tyramine-free diet (cheese, red wine, fermented foods) → risk of hypertensive crisis ("cheese reaction") |
| Moclobemide (reversible MAO-A inhibitor = RIMA) | Safer than irreversible MAOIs; less dietary restriction needed; used for social phobia [1] |
| Contraindications | Concurrent SSRIs/SNRIs/TCAs (serotonin syndrome); tyramine-containing foods (phenelzine); phaeochromocytoma |
Why the tyramine dietary restriction? MAO-A normally breaks down tyramine in the gut. If MAO is inhibited, ingested tyramine is absorbed intact → displaces noradrenaline from sympathetic nerve terminals → massive sympathetic surge → hypertensive crisis. Moclobemide is "reversible" — tyramine can displace it from MAO → less risk.
Beta-adrenergic antagonist e.g. propranolol [1]
| Feature | Detail |
|---|---|
| Mechanism | Blocks β₁ (heart) and β₂ (skeletal muscle, bronchial) adrenergic receptors → ↓tachycardia, ↓tremor, ↓sweating |
| Indication | Relief of sympathetic/peripheral somatic symptoms — particularly useful for performance anxiety (e.g., public speaking, musical performance) [2] |
| Limitation | Does NOT address the cognitive/psychological component of anxiety (worry, apprehension); only treats peripheral symptoms |
| Side effects | Bradycardia, hypotension, bronchospasm, fatigue, cold extremities |
| Contraindications | Asthma/severe COPD (bronchospasm from β₂ blockade), severe bradycardia, heart block, decompensated heart failure, Raynaud's |
Propranolol is the "performance anxiety pill" — a musician with hand tremor before a concert benefits because it blocks the peripheral β-adrenergic manifestations. However, it does nothing for the underlying worry or avoidance.
Benzodiazepines [1]
| Feature | Detail |
|---|---|
| Mechanism | Positive allosteric modulators of GABA-A receptors → enhance GABA-mediated Cl⁻ influx → neuronal hyperpolarisation → ↓excitability of amygdala and CSTC circuits → rapid anxiolysis |
| Onset | Minutes to hours — useful for acute control of anxiety [2] |
| Choice | Usually prefer long-acting BZDs, e.g., diazepam for GAD [2]; high-potency agents (e.g., alprazolam, clonazepam) for panic attacks [2] |
| Duration | Should NOT be prescribed beyond 2–4 weeks to prevent dependence [2] |
| Indications | Acute anxiety crisis, short-term bridging while waiting for SSRI onset, panic attacks (acute), agoraphobia (short-term to aid exposure), specific phobia (PRN for rarely occurring situations e.g., flying) [2] |
| Side effects | Sedation, cognitive impairment, psychomotor slowing, amnesia, paradoxical disinhibition (especially elderly), respiratory depression (especially with opioids/alcohol) |
| Dependence | Physical and psychological dependence develops rapidly (within 2–4 weeks of regular use); withdrawal syndrome (rebound anxiety, insomnia, tremor, seizures — can be life-threatening) |
| Contraindications | History of substance use disorder (high abuse potential), severe respiratory insufficiency, sleep apnoea, myasthenia gravis, severe hepatic impairment, pregnancy (category D — neonatal withdrawal, floppy infant syndrome) |
BZDs: The Short-Term Rule
BZDs should not be used beyond 2–4 weeks [2]. This is one of the most important principles in anxiety management. Longer use leads to tolerance, dependence, cognitive impairment, and a withdrawal syndrome that can itself cause severe anxiety — creating a vicious cycle. BZDs are a bridge, not a destination.
Buspirone [1]
| Feature | Detail |
|---|---|
| Mechanism | 5HT₁A partial agonist → modulates serotonergic system → SSRI-like effect on amygdala and CSTC circuit [2] |
| Onset | Slower onset than BZDs (~4 weeks) [2] — cannot be used for acute anxiety |
| Efficacy | Weaker anxiolytic effect than BZDs but without dependence potential [2] |
| Indications | Useful for short-term control of anxiety or as augmentation to SSRIs [2]; effective in GAD but not in other anxiety disorders [2] |
| Side effects | Insomnia, nausea, agitation [2]; lightheadedness, nervousness, headache |
| Advantages | No sedation, no dependence, no withdrawal, no cognitive impairment, relatively free from drug-drug interactions [2] |
| Contraindications | Concurrent MAOIs; epilepsy (lowers seizure threshold) |
Buspirone occupies a niche role — it's useful when you want an anxiolytic without the dependence/sedation of BZDs, but its slow onset and limited efficacy mean it's rarely used as monotherapy.
Pregabalin [1]
| Feature | Detail |
|---|---|
| Mechanism | Binds α₂δ subunit of presynaptic voltage-dependent Ca²⁺ channels (VDCC) → blocks release of excitatory neurotransmitters, e.g., glutamate [2] |
| Indications | GAD (particularly when not tolerating SRIs); also licensed for neuropathic pain and epilepsy [2] |
| Onset | Faster than SSRIs (within 1 week for some patients) |
| Side effects | Somnolence, dizziness, ↑appetite/weight gain, mood changes, confusion, ataxia, tremor, memory impairment [2]; uncommonly visual disturbances |
| Discontinuation | Insomnia, headache, nausea, diarrhoea, anxiety, sweating, dizziness [2] — taper slowly |
| Contraindications | Caution in renal impairment (renally excreted — dose adjust); growing concern about abuse potential and dependence (especially in patients with substance use history) |
Pregabalin has a different side-effect profile and can be used when not tolerating SRIs [2]. It's increasingly recognised as a useful alternative, particularly for patients who cannot tolerate serotonergic medications.
| Agent | Role | Detail |
|---|---|---|
| Mirtazapine | Monotherapy or adjunctive [2] | NaSSA (noradrenergic and specific serotonergic antidepressant); α₂ antagonist + 5HT2A/2C/3 antagonist + H₁ antagonist. Useful for anxiety with insomnia and weight loss (sedating, appetite-stimulating). S/E: weight gain, sedation |
| Antipsychotics (esp quetiapine) | Not commonly used due to S/E profile [2] | Low-dose quetiapine has anxiolytic effects (H₁ and 5HT2A antagonism); used as augmentation in refractory GAD. S/E: metabolic syndrome, sedation, EPS |
| TCAs | Second-line | As discussed above; not commonly used due to S/E profile [2] |
| α-blockers (prazosin) | PTSD specifically | Prazosin can ↓PTSD symptoms, nightmares, sleep disturbance [2]; blocks α₁-adrenergic receptors → ↓noradrenergic hyperarousal during sleep |
| Second-generation antipsychotics | PTSD augmentation | As monotherapy or augmentation of antidepressants for PTSD [2] |
| Disorder | Mild-Moderate Psychological | Moderate-Severe Psychological | Pharmacological | Notes |
|---|---|---|---|---|
| GAD | Self-help | CBT, applied relaxation | SSRI 1st line; SNRI/pregabalin alternatives; BZDs ≤2–4w for acute; buspirone for augmentation | Stepped care; continue drugs ≥6 months [2] |
| Panic Disorder | Self-help | CBT (targets fears of physical effects; exposure to interoceptive cues) | SSRI 1st line; imipramine (TCA); high-dose BZDs (alprazolam) for acute attacks | Start SSRI low/slow; CBT as effective as antidepressants [2] |
| Social Phobia | Self-help | CBT with social skills training; cognitive treatment for fear of negative evaluation | SSRI 1st line; MAOI (phenelzine) or RIMA (moclobemide) for phobia; β-blockers for performance-only type [1] | |
| Specific Phobia | Self-help | Exposure-based therapy (graded, repeated, prolonged, in vivo > imaginal) | PRN BZD for rarely occurring situations (e.g., flying) — generally pharmacotherapy has limited role | Exposure is mainstay; 70–85% respond [2] |
| Agoraphobia | Self-help | CBT with exposure; resembles panic disorder approach | SSRIs/SNRIs 1st line; TCAs (imipramine, clomipramine); BZDs short-term | Continued for ≥1 year after symptom control [2] |
| PTSD | — | Trauma-focused CBT (1st line); EMDR | SSRIs/SNRIs (augmentation/2nd line); prazosin for nightmares; BZDs for acute hyperarousal [2] | CISD does NOT work; treat comorbid conditions |
| Adjustment Disorder | Problem-solving counselling [2] | Supportive psychotherapy | Anxiolytics/hypnotics may be helpful for a few days [2] | Usually self-limiting |
| Childhood Anxiety | Psychoeducation, educational support | CBT, relaxation training [2] | SSRIs for severe cases; anxiolytics generally avoided [2] | 1st line is psychological; imipramine considered in severe cases |
Special Considerations
Most antidepressants result in ↑anxiety symptoms (apprehension, sleeplessness, palpitations) initially → dose should be increased very slowly [2]
Practical approach:
- GAD/Social anxiety: Start at half the usual antidepressant starting dose (e.g., sertraline 25 mg instead of 50 mg)
- Panic disorder: Start at quarter dose (e.g., sertraline 12.5 mg) — panic patients are exquisitely sensitive to somatic sensations and paradoxical anxiety is particularly distressing
- Increase dose every 1–2 weeks as tolerated
- Can use short-term BZD to cover the initial anxiogenic period
- Continue effective treatment for at least 6 months after symptom control
- For GAD: many guidelines recommend 12–18 months given the chronic relapsing nature
- For PTSD/social anxiety: at least 12 months
- When discontinuing: taper gradually over weeks to months to avoid discontinuation syndrome (especially paroxetine, venlafaxine)
- Relapse rates are significant after discontinuation — discuss with patient
CBT + pharmacotherapy combination may give better response in early stages but long-term results are uncertain [2]
- In practice, combination therapy is commonly used for moderate-severe cases
- The CBT teaches skills that persist after medication is discontinued
- Medication provides symptom relief that allows the patient to engage in CBT more effectively
| Drug Class | Primary Target | Effect on Anxiety Circuit | Onset | Key Limitation |
|---|---|---|---|---|
| SSRIs | SERT blockade → ↑5-HT | ↑Serotonergic modulation of amygdala + CSTC | 2–4 weeks | Initial anxiety worsening |
| SNRIs | SERT + NET blockade → ↑5-HT + ↑NA | Dual modulation of cognitive + somatic anxiety | 2–4 weeks | ↑BP, discontinuation syndrome |
| BZDs | GABA-A potentiation → ↑GABA | Direct suppression of amygdala + CSTC | Minutes | Dependence, cognitive impairment |
| Buspirone | 5-HT₁A partial agonist | Serotonergic modulation (like SSRI) | ~4 weeks | Weak effect; GAD only |
| Pregabalin | α₂δ Ca²⁺ channel ligand → ↓glutamate | ↓Excitatory input to anxiety circuits | ~1 week | Sedation, weight gain, abuse potential |
| β-blockers | β₁/β₂ blockade | ↓Peripheral autonomic symptoms only | Minutes | Does NOT treat central anxiety |
| TCAs | Non-selective SERT + NET blockade | ↑5-HT + ↑NA (like SNRI but less selective) | 2–4 weeks | Cardiac toxicity in OD; anticholinergic S/E |
| MAOIs | MAO inhibition → ↑5-HT, NA, DA | ↑All monoamines | 2–4 weeks | Tyramine crisis; drug interactions |
| Mirtazapine | α₂ + 5HT2/3 + H₁ antagonism | ↑5-HT₁A signalling; antihistamine sedation | 1–2 weeks | Weight gain; sedation |
| Prazosin | α₁-adrenergic blockade | ↓Noradrenergic hyperarousal (especially nocturnal) | Days | Postural hypotension; PTSD-specific |
High Yield Summary — Management of Anxiety Disorders
Hierarchy: Treat substance use first → then determine if anxiety or depression is primary → treat primary condition.
Stepped care: Psychoeducation → self-help → CBT/applied relaxation or SSRI → specialist treatment.
Psychotherapy is first-line and more effective than pharmacotherapy. CBT is the gold standard. Exposure therapy is the mainstay for phobias (70–85% response).
SSRI is first-line pharmacotherapy for all anxiety disorders. Start low, go slow (initial anxiety worsening expected). Continue ≥6 months after response.
BZDs: Only for acute/short-term use (≤2–4 weeks). Long-acting for GAD (diazepam), high-potency for panic (alprazolam).
Key alternatives: SNRI (venlafaxine/duloxetine), pregabalin (GAD if intolerant to SRIs), buspirone (GAD augmentation), β-blockers (performance anxiety only), TCAs (imipramine for panic, clomipramine for OCD), MAOIs/RIMA (phenelzine/moclobemide for phobias).
PTSD: Trauma-focused CBT or EMDR first-line. CISD does NOT work. Prazosin for nightmares.
Referral to secondary care: risk of self-harm/suicide, marked self-neglect, non-response to ≥2 treatments, significant comorbidity.
Active Recall - Management of Anxiety Disorders
References
[1] Lecture slides: GC 167. I feel very nervous Anxiety disorders.pdf (p36, p37, p39) [2] Senior notes: ryanho-psych.md (Sections 8.1.2C Management of GAD, 8.1.3C Management of Panic Disorder, 8.1.4 Management of Phobic Disorders, 8.2 Treatment of PTSD/ASD, 8.3.3 Adjustment Disorder Management, 3.1.4.1 Benzodiazepines, 3.1.4.2 Non-BZD anxiolytics, 3.3 Psychotherapy indications, 12.5 Childhood Anxiety Management, Fig 20.2 Management table) [4] Lecture slides: GC 171. Stress-related disorders and obsessive-compulsive disorder_rev.pdf (p17)
Complications of Anxiety Disorders
Anxiety disorders are not benign conditions that simply cause "worry." Left untreated — or even when partially treated — they produce a cascade of psychiatric, medical, functional, and social complications that are far-reaching and often self-reinforcing. Understanding these complications requires connecting them back to the neurobiology: chronic activation of the amygdala-HPA axis-sympathetic pathways, persistent avoidance behaviour, and the cognitive distortions that drive the disorders all have downstream consequences.
There is a huge amount of suffering associated with these disorders [4].
1. Psychiatric Comorbidities
This is the single most important category of complications. Anxiety disorders rarely exist in isolation — comorbidity is common [1].
Depression is the most frequent and clinically significant comorbidity across all anxiety disorders [1][2].
- 2/3 of GAD patients have other psychiatric diagnosis, with depression being the most common [1]
- Comorbidity of panic disorder: depression [1]
- Co-morbidities of PTSD: depression [4]
- Co-morbidities of OCD: > 60% have lifetime diagnosis of a mood disorder, MDD being the most common [4]
Why does anxiety lead to depression? The mechanism is both neurobiological and psychological:
- Neurobiological: Chronic anxiety → sustained HPA axis activation → ↑cortisol → hippocampal damage (↓volume) + monoamine depletion (5-HT, NA, DA) — the same neurotransmitter systems implicated in depression. The shared serotonin transporter gene polymorphism and shared heritability with neuroticism mean these conditions arise from overlapping biological substrates [2].
- Psychological: Persistent anxiety → avoidance → social withdrawal → loss of positive reinforcement → helplessness and hopelessness → depressive cognitions. The person who avoids social situations due to social anxiety eventually becomes isolated, loses friendships, and feels worthless — a direct pathway to depression.
- Temporal relationship: Anxiety disorders typically precede depression (anxiety has earlier onset — teens/early twenties; depression often develops later). Social anxiety disorder: depression is considered a risk factor for subsequent development [2]. This makes screening for depression in every anxiety patient essential.
Anxiety + Depression = Worse Prognosis
Comorbid anxiety and depression is associated with ↑severity, ↑functional impairment, and ↑duration of illness [2]. These patients are harder to treat, have higher relapse rates, and higher suicide risk than those with either condition alone. The combination warrants aggressive, early treatment.
Other anxiety disorders (e.g., panic, social anxiety) [1]
- Anxiety disorders cluster together. A patient with one anxiety disorder has a markedly elevated risk of having another:
- Why? Shared genetic vulnerability (neuroticism, 5-HT transporter polymorphism), shared neurobiological substrates (amygdala overactivation, CSTC loop dysregulation), and shared psychological risk factors (behavioural inhibition, cognitive biases) mean that vulnerability to one anxiety disorder confers vulnerability to others.
Alcohol and drug abuse [1]
- Comorbidity of panic disorder: alcohol and drug abuse [1]
- Comorbidity for GAD: alcohol and drug abuse [1]
- Co-morbidities of PTSD: substance use disorders [4]
- Agoraphobia: substance use disorder ~1/3 [2]
- Anxiety disorders occur in 32% of alcoholics, often as a form of self-medication [2]
Why does anxiety lead to substance use? The mechanism is straightforward self-medication:
- Alcohol is a GABA-A positive allosteric modulator (similar mechanism to benzodiazepines) → drinking provides rapid anxiolysis by enhancing GABA-mediated inhibition of the amygdala
- Cannabis has anxiolytic properties at low doses via CB₁ receptor activation in the amygdala
- Benzodiazepine misuse/dependence can develop from prescribed or illicitly obtained BZDs
Why is this a complication rather than just a comorbidity? Because substance use creates a vicious cycle:
- Anxiety → alcohol/drug use for relief
- Chronic use → tolerance (need more for the same effect)
- Withdrawal → rebound anxiety that is worse than the original anxiety (because GABA-A receptors have downregulated)
- Worse anxiety → more substance use
- Additional consequences: hepatic damage, social deterioration, accidents, dependence syndrome
Social anxiety disorder: substance abuse is a risk factor for subsequent substance abuse (as coping) [2]. This progression is so predictable that it's essentially a natural history of untreated social anxiety.
Personality disorder (e.g., anankastic, paranoid, avoidant) [1]
- Avoidant personality disorder overlaps extensively with social anxiety disorder (shared heritability ~55%) [2]
- Dependent personality disorder can develop from chronic agoraphobia (patient becomes reliant on companions)
- Anankastic (obsessive-compulsive) personality shares traits with OCD and GAD
- Chronic childhood anxiety, if untreated, can shape personality development in maladaptive directions
| Comorbidity | Mechanism / Context |
|---|---|
| Somatisation | Co-morbidities of PTSD: somatisation [4]. Chronic anxiety → heightened interoception → amplification of normal bodily sensations → repeated presentation with somatic complaints |
| Dissociative disorders | Co-morbidities of PTSD: dissociative disorders [4]. Peritraumatic dissociation during overwhelming stress → persistent dissociative symptoms |
| Tic disorders | OCD: up to 30% have a lifetime tic disorder [4]. Shared CSTC loop pathology |
| Psychotic disorders | OCD: 12% of persons with schizophrenia/schizoaffective disorder have comorbid OCD [4] |
| Eating disorders | Anxiety (especially social anxiety and OCD) increases risk of anorexia nervosa and bulimia through body image preoccupation and perfectionism |
Anxiety disorders, particularly when comorbid with depression, are significant risk factors for suicidal ideation and attempts:
- Panic disorder: acute panic attacks can precipitate impulsive suicidal behaviour during the attack (the overwhelming fear of dying paradoxically can lead to self-harm to "escape" the intolerable state)
- PTSD: high rates of suicidal ideation (particularly following sexual assault or combat)
- Social anxiety disorder: chronic social isolation → depression → suicidality
- Comorbid depression: the strongest mediator of suicide risk in anxiety patients
The presence of an anxiety disorder alongside depression confers a higher suicide risk than depression alone — the agitation and restlessness of anxiety can provide the "energy" to act on suicidal thoughts that depressive psychomotor retardation might otherwise suppress.
Always Assess Suicide Risk
Every patient with an anxiety disorder — especially with comorbid depression, substance use, or PTSD — requires a suicide risk assessment. This is not optional. The chronic suffering, functional impairment, and hopelessness associated with untreated anxiety disorders are potent drivers of suicidal behaviour.
3. Functional Impairment
Anxiety disorders are similar to major depression and chronic diseases such as diabetes in functional impairment and decreased quality of life [4].
This is a critical point that is often underappreciated: anxiety disorders are as disabling as many chronic medical conditions.
- Poor concentration → ↓work performance
- Avoidance → inability to attend meetings, presentations, or work-related social functions
- Panic attacks at work → embarrassment → further avoidance → absenteeism
- GAD: chronic worry → indecisiveness → difficulty completing tasks → job loss
- Social anxiety: inability to function in team settings, networking, interviews → career limitation
- Childhood/adolescent anxiety → school refusal, poor exam performance, difficulty with peer relationships
- Anxiety in childhood may have atypical presentation, e.g., school refusal, frequent somatic complaints, difficulties with peer relationships, low self-esteem [2]
- Test anxiety → underperformance relative to ability
- Social anxiety → inability to participate in group discussions, presentations
- Avoidance behaviour → progressive social isolation
- Social anxiety disorder: only 50% seek treatment, usually after many years of symptoms, and can persist for many years [2]
- Agoraphobia: as the condition progresses, situations are increasingly avoided with shrinkage of 'safe zone', ultimately culminating in confinement to home [2]
- Relationship difficulties: partners may become frustrated with the patient's avoidance; conversely, some partners become "enablers" who accommodate the avoidance (e.g., always accompanying the agoraphobic patient), inadvertently maintaining the disorder
- Selective mutism: prognosis often poor, with 58% remission rate at 13y; associated with later development of phobia, social anxiety, ↑risk for depression, substance misuse in unresolved cases [2]
4. Medical / Physical Complications
Chronic anxiety is not merely a "psychological" problem — it has real, measurable medical consequences through sustained activation of the stress response system.
Impact: associated with functional impairment and ↑cardiovascular mortality [2]
Impact: QoL, functioning and all-cause mortality (especially cardiovascular disorders) [2]
Why does anxiety increase cardiovascular risk? The pathophysiology is multi-layered:
- Chronic sympathetic activation → sustained ↑heart rate, ↑blood pressure → accelerated atherosclerosis, endothelial dysfunction
- HPA axis dysregulation → chronic ↑cortisol → insulin resistance, dyslipidaemia, visceral adiposity → metabolic syndrome → ↑CVD risk
- Platelet hyperactivation: catecholamines activate platelets → ↑thrombotic tendency → ↑risk of MI, stroke
- Autonomic imbalance: ↓parasympathetic (vagal) tone + ↑sympathetic tone → ↓heart rate variability → ↑risk of arrhythmias and sudden cardiac death
- Behavioural mediators: anxiety → physical inactivity (avoidance), poor diet, smoking, alcohol use → additional CVD risk factors
Think of it this way: the fight-or-flight response was designed for brief, intense threats. When it runs continuously for months or years, it's like leaving your car engine redlining — eventually something breaks. The cardiovascular system takes the brunt.
Panic disorder: medical comorbidities (asthma, CAD, HTN, ulcers) [2]
| System | Complication | Mechanism |
|---|---|---|
| Gastrointestinal | Irritable bowel syndrome (IBS), peptic ulcers, functional dyspepsia | Autonomic dysregulation → altered GI motility; chronic cortisol → ↓mucosal protection; brain-gut axis dysfunction |
| Respiratory | Exacerbation of asthma/COPD | Hyperventilation → bronchoconstriction; sympathetic-parasympathetic imbalance; panic-induced bronchospasm |
| Musculoskeletal | Chronic tension-type headache, temporomandibular joint dysfunction, chronic pain syndromes | Sustained muscle tension (sympathetic-mediated); central sensitisation from chronic stress |
| Immune | ↑Susceptibility to infections, autoimmune flares | Chronic cortisol → immune dysregulation (initial immunosuppression → later pro-inflammatory state) |
| Metabolic | Weight gain, metabolic syndrome, type 2 diabetes | HPA axis dysregulation → insulin resistance; comfort eating; medication side effects (pregabalin, mirtazapine) |
| Sleep | Chronic insomnia | Hyperarousal from persistent amygdala/LC activation → difficulty initiating and maintaining sleep |
Anxiety and chronic pain frequently co-occur through shared neurobiological pathways:
- Central sensitisation: chronic anxiety → ↑descending facilitation of pain pathways → ↓pain threshold
- Catastrophising: cognitive bias amplifies pain perception
- Muscle tension: sustained sympathetic activation → tension-type pain
- Shared neurotransmitters: 5-HT and NA modulate both mood and descending pain inhibition — dysfunction in these systems contributes to both anxiety and chronic pain
5. Treatment-Related Complications
Complications can arise not only from the disorder itself but also from its treatment:
- The most common iatrogenic complication of anxiety disorder management
- Develops rapidly (within 2–4 weeks of regular use)
- Withdrawal syndrome: rebound anxiety (often worse than original), insomnia, tremor, perceptual disturbances, seizures (potentially life-threatening)
- Cognitive impairment: ↓memory, ↓psychomotor speed, ↑fall risk (especially elderly)
- Paradoxical disinhibition (especially in elderly, brain-injured, or personality-disordered patients)
- Initial anxiety worsening (first 1–2 weeks) — can cause patients to discontinue treatment prematurely
- Sexual dysfunction — common, persistent, and a major cause of non-adherence
- Discontinuation syndrome (especially paroxetine, venlafaxine) — dizziness, nausea, electric shock sensations ("brain zaps"), anxiety, insomnia
- Hyponatraemia (SIADH) — especially in elderly patients; can present with confusion, seizures
- QTc prolongation — especially citalopram/escitalopram at higher doses → risk of torsades de pointes
- Serotonin syndrome — if combined with MAOIs or other serotonergic agents (fever, agitation, clonus, diaphoresis — medical emergency)
- Many patients with anxiety disorders (particularly social anxiety and agoraphobia) avoid seeking treatment due to the nature of their condition — the very symptoms prevent help-seeking
- Only 50% of social anxiety patients seek treatment, usually after many years [2]
- This delay allows complications to accumulate
Anxiety disorders have a waxing and waning course over lifetime [4].
| Disorder | Course Complication |
|---|---|
| GAD | Generally poor prognosis if disease lasts > 6 months; only 60% complete recovery after 12 years; 50% of those recovering have subsequent relapses [2] |
| Panic disorder | Course tends to be recurrent and chronic with fluctuating anxiety and depression; remission in 64% at 2 years [2] |
| Social anxiety | Can persist for many years; chronic course [2] |
| Specific phobia | Tends to be lifelong when untreated [2] |
| Agoraphobia | Generally with gradual deterioration and chronic + unremitting without treatment [2] |
| Childhood anxiety | Nearly 2/3 expected to disappear in 3–5 years, but ~1/3 will have other categories of anxiety disorders at follow-up [2] |
The natural history of untreated anxiety is not self-resolution — it's chronicity, accumulation of comorbidities, and progressive functional decline. This is why early, aggressive treatment matters.
Anxiety disorders in childhood have specific developmental complications:
- Academic trajectory: school refusal and test anxiety → academic underperformance → limited educational attainment
- Social development: avoidance of peer interactions → impaired social skills development → ↑risk of social anxiety persisting into adulthood
- Personality formation: chronic behavioural inhibition and avoidance → development of avoidant or dependent personality traits
- Transition to adult psychopathology: ~1/3 of childhood anxiety disorders will develop other categories of anxiety disorders at follow-up [2]; selective mutism associated with later development of phobia, social anxiety, ↑risk for depression, substance misuse in unresolved cases [2]
High Yield Summary — Complications of Anxiety Disorders
Psychiatric comorbidities are the most important complications:
- Depression: most common; 2/3 of GAD patients have comorbid psychiatric diagnoses; anxiety typically precedes depression
- Other anxiety disorders: cluster together due to shared neurobiology
- Substance use: self-medication with alcohol/drugs creates a vicious cycle of rebound anxiety
- Personality disorders: especially avoidant PD with social anxiety
Suicide risk: elevated, particularly with comorbid depression, PTSD, and substance use. Always assess.
Functional impairment: equivalent to diabetes and major depression in disability. Occupational, academic, social, and interpersonal domains all affected.
Cardiovascular mortality: chronic sympathetic/HPA activation → HTN, atherosclerosis, arrhythmias, ↑all-cause mortality.
Medical comorbidities: IBS, chronic pain, asthma exacerbation, metabolic syndrome, insomnia.
Treatment complications: BZD dependence (if used > 2-4 weeks), SSRI initial worsening, sexual dysfunction, discontinuation syndrome, hyponatraemia.
Chronicity: Without treatment, anxiety disorders are chronic, relapsing conditions with progressive functional decline. Only 60% GAD recovery at 12 years; specific phobias are lifelong if untreated; agoraphobia progressively worsens.
Childhood complications: school refusal, impaired social development, personality formation disruption, 1/3 transition to other anxiety disorders.
Active Recall - Complications of Anxiety Disorders
References
[1] Lecture slides: GC 167. I feel very nervous Anxiety disorders.pdf (p8, p17, p30) [2] Senior notes: ryanho-psych.md (Sections 8.1.2 GAD epidemiology/course/comorbidities, 8.1.3 Panic Disorder course and prognosis, 8.1.4 Phobic Disorders course/comorbidities, 5.2 Psychiatric comorbidity in alcoholism, 12.5 Childhood Anxiety Disorders prognosis) [4] Lecture slides: GC 171. Stress-related disorders and obsessive-compulsive disorder_rev.pdf (p16, p26, p38, p43)
High Yield Summary
Definition: Anxiety disorders = excessive, persistent, disproportionate fear/anxiety → distress + functional impairment.
Epidemiology: Most common psychiatric disorders; early onset (teens-20s); F:M = 2:1; high comorbidity with depression and substance use.
Two key circuits: (1) Amygdala-based fear circuit → autonomic/somatic symptoms; (2) CSTC loop → worry/rumination.
Three key neurotransmitters: GABA (inhibitory, ↓ in anxiety → BZDs), serotonin (restrains anxiety behaviour → SSRIs), noradrenaline (autonomic arousal → SNRIs, β-blockers).
5 A's of anxiety: Apprehension, Arousal, Anticipatory anxiety, Avoidance, Autonomic activation.
Aetiology: Biopsychosocial — genetics (moderate, shared with depression), neurobiological (amygdala overactivation, mPFC failure), personality (neuroticism, behavioural inhibition), cognitive biases, early adversity, social factors.
Always rule out: Medical causes (thyrotoxicosis, hypoglycaemia, phaeochromocytoma, PE, arrhythmia), substance intoxication/withdrawal, medication side effects.
DSM-5 classification: GAD, panic disorder, agoraphobia, social anxiety disorder, specific phobia, separation anxiety disorder, selective mutism. OCD and PTSD are in SEPARATE chapters.
Panic attacks can occur in any anxiety disorder but are only "unexpected" in panic disorder.
Blood-injection-injury phobia = unique diphasic vasovagal response (not pure sympathetic).
High Yield Summary — Differential Diagnosis of Anxiety Disorders
Step 1: Exclude organic causes (thyrotoxicosis, hypoglycaemia, phaeochromocytoma, cardiac arrhythmia, PE, TLE, vestibular dysfunction) — always check TFTs and glucose at minimum.
Step 2: Exclude substance-induced anxiety (intoxication: stimulants, caffeine, cannabis; withdrawal: alcohol, BZDs; medication S/E: SSRIs early, steroids, T4).
Step 3: Exclude higher-order psychiatric disorders (psychosis → mood disorders → then anxiety).
Key differentiators between anxiety disorders: Identify the focus of fear and the pattern (continuous vs. episodic; expected vs. unexpected).
- GAD: free-floating, multiple topics, continuous, ≥6 months
- Panic disorder: unexpected panic attacks + persistent worry about attacks
- Social anxiety: fear of scrutiny/negative evaluation in social situations
- Specific phobia: circumscribed fear of specific object/situation
- Agoraphobia: fear of being unable to escape/get help (crowds, open/enclosed spaces)
- PTSD: follows trauma; re-experiencing + avoidance + hyperarousal
- OCD: ego-dystonic obsessions + ritualistic compulsions
2/3 of GAD patients have comorbid psychiatric diagnoses — depression, other anxiety disorders, personality disorders, substance use.
Adjustment disorder is a residual category — only diagnosed when no other specific disorder criteria are met.
High Yield Summary — Diagnostic Criteria and Investigation
All anxiety disorders share: core symptom cluster + trigger specificity + duration threshold (usually ≥6 months except panic disorder ≥1 month, PTSD > 1 month, adjustment disorder onset ≤3 months) + significant distress/impairment + exclusion of substance/medical/other mental disorder.
GAD criteria (REDIMS): Excessive worry ≥6 months + ≥3 of Restlessness, Easy fatigue, Difficulty concentrating, Irritability, Muscle tension, Sleep disturbance.
Panic disorder: Recurrent UNEXPECTED panic attacks (≥4/13 symptoms, peak in minutes) + ≥1 month persistent concern or behavioural change.
Specific phobia: Marked fear of specific stimulus; almost always provokes fear; out of proportion; ≥6 months; distress/impairment.
Social anxiety: Fear of social scrutiny/negative evaluation; ≥6 months; distress/impairment. Specifier: "performance only."
Agoraphobia: Fear of ≥2/5 situations (public transport, open spaces, enclosed places, crowds, alone outside); fears inability to escape/get help; ≥6 months.
ICD-10 vs DSM-5: ICD-10 treats GAD as diagnosis of exclusion; DSM-5 allows comorbid diagnosis.
Essential investigations: TFTs, glucose, ECG (also baseline for SSRIs/TCAs), Ca²⁺, FBC, U&E, LFTs. Consider 24h urinary catecholamines (phaeochromocytoma), EEG (TLE), urine drug screen.
Screening tools: GAD-7 (anxiety), PHQ-9 (depression comorbidity), BAI, HAM-A.
Diagnosis is clinical — investigations exclude organic mimics and establish treatment baselines.
High Yield Summary — Management of Anxiety Disorders
Hierarchy: Treat substance use first → then determine if anxiety or depression is primary → treat primary condition.
Stepped care: Psychoeducation → self-help → CBT/applied relaxation or SSRI → specialist treatment.
Psychotherapy is first-line and more effective than pharmacotherapy. CBT is the gold standard. Exposure therapy is the mainstay for phobias (70–85% response).
SSRI is first-line pharmacotherapy for all anxiety disorders. Start low, go slow (initial anxiety worsening expected). Continue ≥6 months after response.
BZDs: Only for acute/short-term use (≤2–4 weeks). Long-acting for GAD (diazepam), high-potency for panic (alprazolam).
Key alternatives: SNRI (venlafaxine/duloxetine), pregabalin (GAD if intolerant to SRIs), buspirone (GAD augmentation), β-blockers (performance anxiety only), TCAs (imipramine for panic, clomipramine for OCD), MAOIs/RIMA (phenelzine/moclobemide for phobias).
PTSD: Trauma-focused CBT or EMDR first-line. CISD does NOT work. Prazosin for nightmares.
Referral to secondary care: risk of self-harm/suicide, marked self-neglect, non-response to ≥2 treatments, significant comorbidity.
High Yield Summary — Complications of Anxiety Disorders
Psychiatric comorbidities are the most important complications:
- Depression: most common; 2/3 of GAD patients have comorbid psychiatric diagnoses; anxiety typically precedes depression
- Other anxiety disorders: cluster together due to shared neurobiology
- Substance use: self-medication with alcohol/drugs creates a vicious cycle of rebound anxiety
- Personality disorders: especially avoidant PD with social anxiety
Suicide risk: elevated, particularly with comorbid depression, PTSD, and substance use. Always assess.
Functional impairment: equivalent to diabetes and major depression in disability. Occupational, academic, social, and interpersonal domains all affected.
Cardiovascular mortality: chronic sympathetic/HPA activation → HTN, atherosclerosis, arrhythmias, ↑all-cause mortality.
Medical comorbidities: IBS, chronic pain, asthma exacerbation, metabolic syndrome, insomnia.
Treatment complications: BZD dependence (if used > 2-4 weeks), SSRI initial worsening, sexual dysfunction, discontinuation syndrome, hyponatraemia.
Chronicity: Without treatment, anxiety disorders are chronic, relapsing conditions with progressive functional decline. Only 60% GAD recovery at 12 years; specific phobias are lifelong if untreated; agoraphobia progressively worsens.
Childhood complications: school refusal, impaired social development, personality formation disruption, 1/3 transition to other anxiety disorders.
Major Depressive Disorder
Major depressive disorder is a psychiatric condition characterized by persistent depressed mood or loss of interest (anhedonia) lasting at least two weeks, accompanied by neurovegetative symptoms such as sleep disturbance, appetite changes, fatigue, and impaired concentration, causing significant functional impairment.
Obsessive-compulsive Disorder
Obsessive-compulsive disorder is a chronic psychiatric condition characterized by intrusive, unwanted thoughts (obsessions) and repetitive behaviors or mental acts (compulsions) performed to reduce the resulting anxiety.