Psychiatry & Mental Health

Key Facts

TRD represents a significant clinical challenge, affecting approximately one-third of patients with depression. Systematic evaluation and a stepped-care approach are essential.

Epidemiology

Of the approximately 3.3 million adults treated for depression in the UK annually, approximately 1 million experience TRD. TRD is associated with significantly higher healthcare costs (estimated 3-6× higher than responsive depression) and poorer functional outcomes.

Aetiology

Factors contributing to poor treatment response:

• Pharmacological: Inadequate dose or duration, poor adherence, pharmacokinetic factors (CYP450 rapid metabolisers)
• Clinical: Comorbid anxiety, personality disorder, substance misuse, chronic pain, medical comorbidity
• Diagnostic: Undiagnosed bipolar disorder, ADHD, hypothyroidism, neurodegenerative disease
• Psychosocial: Ongoing adversity, social isolation, unemployment, trauma

Pathophysiology

TRD may involve:

• Glutamate system dysfunction: Basis for ketamine/esketamine treatment (NMDA receptor antagonism)
• HPA axis hyperactivity: Persistent cortisol elevation despite treatment
• Neuroinflammation: Elevated CRP and cytokines predict poor SSRI response
• Altered neuroplasticity: Impaired BDNF signalling - may explain delayed onset of antidepressant effect
• Epigenetic modifications: Stress-induced changes in gene expression affecting serotonergic/glutamatergic systems

Clinical Assessment in TRD

• Persistent depressive symptoms despite ≥2 adequate antidepressant trials
• Often significant functional impairment, social withdrawal, inability to work
• High rate of comorbid anxiety (>60%), personality disorder, substance misuse
• Increased suicide risk compared to treatment-responsive depression

Before Diagnosing TRD - Exclude

• Non-adherence: Up to 50% of patients do not take antidepressants as prescribed
• Inadequate trial: Subtherapeutic dose or insufficient duration (<6 weeks)
• Incorrect diagnosis: Bipolar depression, personality disorder, ADHD, organic cause
• Comorbid substance misuse: Alcohol and drugs can negate antidepressant effects
• Untreated medical conditions: Hypothyroidism, anaemia, chronic pain, sleep disorders

Red Flags

• Escalating suicidal ideation despite treatment optimisation
• Psychotic symptoms developing during depressive episode
• Severe self-neglect, catatonia, refusal to eat/drink - consider ECT
• Rapid cycling mood - reconsider bipolar diagnosis

Bedside

• Medication review: Confirm adequate dose, duration, and adherence for each trial
• PHQ-9: Quantify current severity and track response
• Risk assessment: Comprehensive suicide risk evaluation
• Substance use assessment: AUDIT-C, DAST-10

Bloods

• TFTs: Exclude hypothyroidism (even subclinical)
• FBC, B12, folate: Nutritional deficiencies
• Lithium level: If on lithium augmentation (target 0.4-0.8 mmol/L for augmentation)
• Renal function, calcium: Baseline for lithium
• CRP: Emerging evidence that elevated CRP predicts better response to nortriptyline vs SSRI

Special Tests

• Psychiatric review: Detailed reassessment of diagnosis, comorbidity, psychosocial factors
• Neuroimaging: Consider if organic cause suspected (e.g., space-occupying lesion)
• Pharmacogenomic testing: Emerging - CYP2D6, CYP2C19 genotyping may guide antidepressant choice (not yet routinely recommended by NICE)

Non-pharmacological

• CBT: Evidence for TRD when added to medication (CoBalT trial)
• Behavioural activation: Structured activity scheduling
• Mindfulness-based cognitive therapy (MBCT): Reduces relapse risk
• ECT: Indicated for severe TRD, psychotic depression, catatonia, life-threatening depression - bilateral typically more effective; 6-12 sessions
• Repetitive transcranial magnetic stimulation (rTMS): NICE-approved for TRD; non-invasive

Pharmacological

Switching strategies:

• Within class: SSRI → different SSRI
• Between classes: SSRI → SNRI (venlafaxine 225-375mg) or mirtazapine
• Combination: SSRI + mirtazapine ("California rocket fuel" with venlafaxine + mirtazapine)

Augmentation strategies:

• Lithium: 400-800mg OD (target 0.4-0.8 mmol/L) - strongest evidence base
• Quetiapine: 50-300mg (low-dose, off-label for augmentation)
• Aripiprazole: 2.5-10mg OD
• Triiodothyronine (T3): 20-50mcg OD - evidence primarily from STAR*D

Newer treatments:

• Esketamine nasal spray (Spravato): NICE TA854 - for TRD with SSRI/SNRI; administered under supervision, monitoring for 2 hours post-dose
• Psilocybin-assisted therapy: Under investigation; not yet approved

Referral Criteria

• Failed 2 adequate antidepressant trials - secondary care psychiatry
• Consideration for ECT - specialist unit
• Consideration for esketamine - specialist centre
• Complex comorbidity - multidisciplinary team assessment

• STAR*D trial: Cumulative remission rate ~67% after 4 treatment steps; but higher relapse rates with each subsequent step
• ECT: Response rates 50-70% in TRD; relapse rate ~50% within 6 months without continuation pharmacotherapy
• Lithium augmentation: Response rate approximately 40-50% in TRD
• Esketamine: Approximately 70% response rate in clinical trials; rapid onset (hours to days)
• Long-term: TRD associated with 2-3× higher suicide risk, longer hospital admissions, and significantly impaired quality of life
• Combination of pharmacological and psychological approaches gives the best outcomes

STAR*D Trial Summary

TRD Treatment Algorithm

Key Facts

Bipolar disorder is a chronic, relapsing mood disorder with alternating episodes of mania/hypomania and depression. It requires long-term pharmacological management and is associated with significant functional impairment and suicide risk.

Epidemiology

Lifetime prevalence of bipolar disorder is approximately 1-2%. Equal sex distribution (unlike unipolar depression). Mean age of onset is 25 years, but there is typically a 9-year delay to correct diagnosis. Bipolar disorder has a strong genetic component (heritability ~85%).

Aetiology

• Genetic: Heritability ~85%; multiple genes involved (CACNA1C, ANK3, DGKH); concordance in monozygotic twins ~70%
• Neurochemical: Dopamine excess (mania), serotonin/noradrenaline deficiency (depression), glutamate/GABA imbalance
• Neuroanatomical: Prefrontal cortex hypoactivity, amygdala hyperactivity, reduced grey matter volume
• Psychosocial: Life events can trigger episodes; disrupted circadian rhythms; sleep deprivation can precipitate mania

Pathophysiology

• Kindling hypothesis: Repeated episodes lower the threshold for future episodes, eventually occurring spontaneously
• Circadian rhythm disruption: Social rhythm therapy targets this mechanism
• Mitochondrial dysfunction: Emerging evidence of bioenergetic impairment
• Second messenger systems: Lithium inhibits inositol monophosphatase and GSK-3β, modulating intracellular signalling

Mania (≥7 days)

• Elevated or irritable mood - inappropriately cheerful or hostile
• Grandiosity - inflated self-esteem, may be delusional
• Decreased need for sleep - feels rested after 2-3 hours
• Pressured speech - rapid, difficult to interrupt
• Flight of ideas - racing thoughts, loosening of associations
• Distractibility and increased goal-directed activity
• Reckless behaviour - spending sprees, sexual indiscretions, risky investments
• Psychotic features may occur (mood-congruent delusions of grandeur, hallucinations)

Hypomania (≥4 days)

• Similar to mania but milder; no psychosis; social functioning may be enhanced or mildly impaired

Bipolar Depression

• Similar to unipolar depression; often more atypical features (hypersomnia, hyperphagia, leaden paralysis)
• Psychomotor retardation more prominent

Red Flags

• Manic episode with psychotic features - may need urgent admission under Mental Health Act
• Rapid cycling (≥4 episodes/year) - associated with poorer prognosis
• Mixed features (simultaneous manic and depressive symptoms) - high suicide risk
• Lithium level >1.5 mmol/L - toxicity, urgent management

Bedside

• MDQ (Mood Disorder Questionnaire): Screening tool for bipolar disorder
• Risk assessment: Suicide risk, risk to others (especially in mania)
• Functional assessment: Impact on work, relationships, finances
• Collateral history: Essential - patients in mania often lack insight

Bloods

• TFTs: Exclude hyperthyroidism (mania mimic); baseline before lithium (lithium causes hypothyroidism)
• U&Es, eGFR: Baseline renal function (lithium nephrotoxicity)
• Calcium: Lithium can cause hyperparathyroidism
• FBC, LFTs: Baseline for valproate monitoring
• Lithium level: Trough level 12 hours post-dose; target 0.6-0.8 mmol/L maintenance
• Pregnancy test: Before starting valproate (teratogenic)

Special Tests

• ECG: QTc baseline (some mood stabilisers/antipsychotics prolong QT)
• Urine drug screen: Exclude substance-induced presentation
• Neuroimaging: If organic cause suspected (first episode mania in elderly)

Non-pharmacological

• Psychoeducation: Understanding illness, recognising early warning signs of relapse
• CBT for bipolar: Evidence for relapse prevention
• Family-focused therapy: Reduces relapse rates
• Social rhythm therapy: Stabilise daily routines and circadian rhythms
• Advance care planning: Crisis plan, preferences for treatment during episodes

Pharmacological

Acute mania (NICE CG185):

• Stop antidepressants
• First-line: Haloperidol 5-10mg, olanzapine 10-15mg, quetiapine 400-800mg, or risperidone 2-6mg
• If already on lithium/valproate: optimise dose; add antipsychotic if needed
• Severe mania: Consider combination antipsychotic + mood stabiliser

Bipolar depression:

• First-line: Quetiapine 300mg OD (monotherapy) or fluoxetine + olanzapine combination
• Lamotrigine 25mg OD titrated slowly to 200mg (effective for depressive episodes, less for mania)
• Antidepressant monotherapy AVOIDED (risk of manic switch) - if used, always with mood stabiliser

Long-term prophylaxis:

• Lithium: First-line; 400-1200mg OD/BD; monitoring: levels 3-monthly (stable), renal/thyroid 6-monthly
• Valproate: 500-2000mg daily; NOT for women of childbearing potential
• Lamotrigine: Effective for bipolar depression prevention; titrate slowly (SJS risk)
• Olanzapine, quetiapine: If mood stabilisers inadequate/not tolerated

Referral Criteria

• All suspected bipolar disorder - secondary care psychiatry for confirmation and initiation of treatment
• Acute mania - consider crisis team or inpatient admission (may require MHA)
• Treatment resistance - specialist mood disorders service

• Chronic relapsing course: Average 8-10 mood episodes over lifetime
• Suicide: 15-20× general population risk; ~25-50% attempt suicide; ~5-10% die by suicide
• Functional impairment: Even between episodes, cognitive and occupational impairment is common
• Lithium: Reduces suicide risk by approximately 60% and relapse rate by ~40%
• Rapid cycling: Poorer prognosis; lithium less effective - consider valproate (if not contraindicated) or lamotrigine
• Comorbid substance misuse worsens prognosis significantly

Lithium Monitoring Schedule

Lithium Toxicity - Signs by Level

Drugs That Increase Lithium Levels

Key Facts

GAD is one of the most common anxiety disorders, characterised by persistent, excessive, and difficult-to-control worry about everyday events. It causes significant psychological distress and physical symptoms.

Epidemiology

Lifetime prevalence of GAD is 5-6%; 12-month prevalence 2-3%. Women are approximately twice as commonly affected as men. GAD often has a chronic course and is the most common anxiety disorder in older adults. It is frequently comorbid with depression (60%), other anxiety disorders, and substance misuse.

Aetiology

• Genetic: Heritability ~30%; shared genetic susceptibility with depression
• Neurobiological: Amygdala hyperactivation, prefrontal cortex hypofunction, altered GABA/serotonin/noradrenaline signalling
• Psychological: Intolerance of uncertainty model (Dugas); metacognitive model (Wells) - "worry about worry"
• Environmental: Adverse childhood experiences, insecure attachment, chronic stress

Pathophysiology

• Amygdala hyperactivity: Exaggerated threat detection and fear response
• Prefrontal cortex dysfunction: Impaired top-down emotional regulation
• HPA axis: Chronic stress response with elevated cortisol
• GABA deficiency: Reduced GABAergic inhibition - target of benzodiazepines and pregabalin
• Autonomic nervous system dysregulation: Reduced heart rate variability, chronic sympathetic activation

Core Features (≥6 months)

• Excessive worry about multiple everyday events (work, health, finances, family)
• Difficulty controlling the worry
• Physical symptoms: Muscle tension, restlessness, fatigue, difficulty concentrating, irritability, sleep disturbance

Associated Features

• Autonomic hyperarousal: Palpitations, sweating, dry mouth, dizziness, GI symptoms
• Hypervigilance and exaggerated startle response
• Avoidance behaviours
• Functional impairment in work and relationships

Red Flags

• Coexisting severe depression - assess suicide risk
• Substance misuse (self-medication with alcohol/benzodiazepines)
• Panic attacks - may indicate comorbid panic disorder
• Physical symptoms mimicking medical conditions - exclude organic cause

Bedside

• GAD-7: 7-item screening questionnaire (0-4 minimal, 5-9 mild, 10-14 moderate, 15-21 severe)
• PHQ-9: Screen for comorbid depression
• Functional assessment: Impact on daily life, work, relationships

Bloods

• TFTs: Exclude hyperthyroidism
• FBC: Anaemia can cause anxiety-like symptoms
• HbA1c, fasting glucose: Hypoglycaemia can mimic anxiety
• U&Es: Baseline if starting medication

Special Tests

• ECG: If palpitations prominent - exclude arrhythmia; baseline for SSRIs (QTc)
• 24h urine catecholamines/metanephrines: If phaeochromocytoma suspected

Non-pharmacological

• Step 1: Education about GAD, active monitoring
• Step 2: Guided self-help (based on CBT principles), psychoeducation groups
• Step 3: CBT (12-15 sessions) - most effective psychological therapy for GAD; applied relaxation
• All steps: Exercise, sleep hygiene, caffeine/alcohol reduction, mindfulness

Pharmacological (NICE CG113)

• First-line: Sertraline 50mg OD (titrate to 200mg); alternatives: escitalopram 10-20mg, paroxetine 20-50mg
• SNRI: Venlafaxine 75-225mg or duloxetine 60-120mg if SSRI ineffective
• Second-line: Pregabalin 150mg daily in divided doses, titrate to max 600mg/day
• Short-term crisis: Benzodiazepines (diazepam 2-5mg TDS) for maximum 2-4 weeks
• Buspirone: 5-15mg BD - alternative if others not tolerated (slow onset, 2-4 weeks)
• Beta-blockers: Propranolol 10-40mg TDS for physical symptoms (tremor, palpitations) - does not treat psychological symptoms

Referral Criteria

• Step 3 treatment failure - specialist anxiety disorder service
• Significant comorbidity (severe depression, substance misuse, personality disorder)
• Risk of suicide or self-harm
• Complex presentation or diagnostic uncertainty

• Chronic course: GAD is often persistent; ~50% have symptoms >5 years
• Remission: ~38% remit within 2 years with treatment; higher with combined CBT + pharmacotherapy
• Comorbidity: ~60% with comorbid depression; ~50% with other anxiety disorders
• Functional impact: Significant reduction in quality of life, work productivity, and social functioning
• CBT: ~50-60% response rate; benefits maintained at follow-up
• SSRIs: ~50-60% response rate; relapse common on discontinuation (continue for ≥12 months after remission)

GAD-7 Scoring

Stepped Care Model (NICE CG113)

Key Facts

Panic disorder involves recurrent unexpected panic attacks and persistent concern about their implications. Panic attacks are sudden surges of intense fear accompanied by physical and cognitive symptoms, peaking within minutes.

Epidemiology

Lifetime prevalence is 2-3%; 12-month prevalence ~1.5%. Women are twice as commonly affected. Age of onset is typically late teens to mid-30s. Panic disorder is frequently comorbid with agoraphobia (~30-50%), depression (~50%), and other anxiety disorders.

Aetiology

• Genetic: Heritability ~40%; first-degree relatives have 4-8× increased risk
• Neurobiological: Amygdala hyperreactivity, locus coeruleus (noradrenergic) overactivity, serotonergic dysfunction
• Cognitive: Catastrophic misinterpretation of bodily sensations (Clark's cognitive model) - e.g., palpitations → "I'm having a heart attack"
• Respiratory: CO2 hypersensitivity theory - panic-prone individuals have lower threshold for CO2-induced anxiety
• Psychosocial: Stressful life events, childhood separation anxiety, parental overprotection

Pathophysiology

• False suffocation alarm theory (Klein): Brainstem CO2 monitor is overly sensitive → triggers alarm response inappropriately
• Sympathetic nervous system activation: Adrenaline surge → tachycardia, sweating, tremor, hyperventilation

Panic Attack Symptoms (≥4 of the following)

• Palpitations or accelerated heart rate
• Sweating
• Trembling or shaking
• Shortness of breath or feeling of smothering
• Chest pain or discomfort
• Nausea or abdominal distress
• Dizziness, light-headedness, or feeling faint
• Chills or hot flushes
• Paraesthesia (numbness or tingling)
• Derealisation or depersonalisation
• Fear of losing control or "going crazy"
• Fear of dying

Associated Features

• Anticipatory anxiety: Persistent worry about when next attack will occur
• Avoidance: Avoiding situations associated with attacks (may develop into agoraphobia)
• Nocturnal panic attacks: Wake from sleep with panic (differentiate from sleep apnoea, cardiac arrhythmia)

Red Flags - Exclude Medical Causes

• Chest pain with cardiac risk factors - ECG, troponin
• Syncope - cardiac arrhythmia assessment
• Weight loss, tremor, heat intolerance - thyrotoxicosis
• Episodes always related to specific trigger - consider phobia rather than panic disorder

Bedside

• GAD-7 and PHQ-9: Screen for comorbid GAD and depression
• Panic Disorder Severity Scale (PDSS): Quantify severity
• Risk assessment: Suicide risk, self-harm, substance misuse

Bloods

• TFTs: Exclude hyperthyroidism
• FBC, glucose: Anaemia, hypoglycaemia
• U&Es, calcium: Electrolyte abnormalities

Special Tests

• ECG: Exclude arrhythmia, QTc prolongation baseline
• Echocardiogram: If cardiac symptoms concerning
• Holter monitor: If palpitations not captured on ECG

Non-pharmacological

• CBT: First-line psychological therapy - Clark's cognitive model
  • Psychoeducation about panic cycle
  • Cognitive restructuring of catastrophic misinterpretations
  • Interoceptive exposure (deliberately inducing feared sensations - e.g., hyperventilation, spinning)
  • Behavioural experiments to test catastrophic predictions
• Guided self-help: Based on CBT principles
• Breathing retraining: Slow diaphragmatic breathing

Pharmacological (NICE CG113)

• First-line: SSRI - sertraline 50mg OD or citalopram 10-20mg OD (start low, increase slowly - SSRIs can initially worsen anxiety)
• Second-line: SNRI - venlafaxine 75-225mg; or imipramine (TCA) if SSRIs/SNRIs not tolerated
• Short-term crisis only: Benzodiazepines (diazepam 2-5mg PRN) - maximum 2-4 weeks
• Not recommended: Beta-blockers (ineffective for panic disorder, unlike performance anxiety)

Referral Criteria

• Failed first-line SSRI + CBT - secondary care
• Severe agoraphobia preventing engagement with treatment
• Significant comorbidity (depression, substance misuse)
• Diagnostic uncertainty

• CBT: 70-90% response rate; gains generally maintained at 2-year follow-up
• SSRIs: 50-60% response rate; ~30% relapse on discontinuation
• Combined CBT + SSRI: Best outcomes in moderate-severe panic disorder
• Natural course: Without treatment, panic disorder tends to be chronic with waxing and waning; spontaneous remission in ~30-40%
• Agoraphobia: Develops in ~30-50% if untreated; significantly worsens prognosis
• Mortality: No increased all-cause mortality, but significant functional impairment and reduced quality of life

Clark's Cognitive Model of Panic

Panic Disorder vs GAD

Key Facts

OCD is a chronic neuropsychiatric disorder characterised by obsessions and compulsions that are time-consuming, distressing, and functionally impairing. It is one of the most disabling psychiatric conditions.

Epidemiology

Lifetime prevalence is 2-3%. Equal sex distribution overall, but males have earlier onset. Mean age of onset is 19-20 years (bimodal: childhood peak ~10 years, adult peak ~21 years). Average delay to treatment is 7-10 years. OCD accounts for significant disability - ranked by WHO as one of the top 10 most disabling conditions.

Aetiology

• Genetic: Heritability ~40-50%; first-degree relatives have 4× increased risk
• Neuroanatomical: Cortico-striato-thalamo-cortical (CSTC) circuit dysfunction - orbitofrontal cortex and caudate nucleus hyperactivity
• Serotonergic: Serotonin dysfunction - basis for SSRI treatment
• Autoimmune: PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) - abrupt OCD onset post-streptococcal infection in children
• Psychological: Inflated responsibility beliefs, thought-action fusion, intolerance of uncertainty

Pathophysiology

• Serotonin hypothesis: Supported by selective response to serotonergic drugs (SSRIs, clomipramine) but not noradrenergic drugs
• Glutamate dysfunction: Emerging evidence - riluzole and memantine under investigation
• ERP mechanism: Habituation - repeated exposure to anxiety-provoking stimuli without performing compulsion leads to anxiety reduction over time

Common Obsession Themes

• Contamination: Fear of germs, dirt, bodily fluids → washing/cleaning compulsions
• Harm: Fear of causing harm to self or others → checking compulsions
• Symmetry/ordering: Need for things to be "just right" → arranging, counting
• Forbidden thoughts: Intrusive sexual, religious, or aggressive thoughts → mental rituals, reassurance-seeking

Common Compulsion Types

• Washing and cleaning
• Checking (locks, appliances, safety)
• Counting, ordering, arranging
• Mental rituals (praying, repeating words)
• Reassurance-seeking
• Hoarding (may overlap with hoarding disorder)

Key Clinical Features

• Patient recognises thoughts are their own (not inserted) and usually recognises they are excessive/irrational
• Attempts to resist compulsions cause mounting anxiety
• Symptoms are time-consuming (>1 hour/day) and cause significant distress or functional impairment

Red Flags

• Severe OCD with total functional impairment - consider specialist inpatient OCD unit
• OCD with psychotic features - poor insight subtype, consider antipsychotic augmentation
• Sudden onset OCD in child post-streptococcal infection - PANDAS, consider paediatric referral
• Suicidal ideation - comprehensive risk assessment

Bedside

• Y-BOCS: Gold standard severity rating (0-40); mild <16, moderate 16-23, severe 24-31, extreme 32-40
• OCI-R (Obsessive-Compulsive Inventory-Revised): Self-report screening tool
• PHQ-9/GAD-7: Screen for comorbid depression and anxiety
• Risk assessment: Suicidal ideation, self-harm

Bloods

• TFTs: Exclude thyroid dysfunction
• FBC: Baseline if starting clomipramine
• ASOT/anti-DNase B: If PANDAS suspected in children

Special Tests

• ECG: Before clomipramine (cardiotoxic); baseline for SSRIs at high doses
• Neuropsychological testing: If cognitive concerns or diagnostic uncertainty
• Neuroimaging: Not routine - research shows OFC and caudate hyperactivity on fMRI

Non-pharmacological

• Mild OCD: Low-intensity CBT (guided self-help with ERP)
• Moderate-severe OCD: High-intensity CBT with ERP (specialist therapist, 12-20 sessions)
• ERP protocol: Graded exposure to feared stimuli + prevention of compulsive response → habituation
• Family involvement: Psychoeducation, reducing accommodation of compulsions

Pharmacological (NICE CG31)

• First-line SSRI (higher doses than for depression):
  • Fluoxetine 60-80mg OD
  • Sertraline 200mg OD
  • Fluvoxamine 100-300mg OD
  • Paroxetine 40-60mg OD
• Allow 8-12 weeks at adequate dose before concluding ineffective (longer than depression)
• Second-line: Clomipramine 75-250mg OD (most effective single agent, but anticholinergic/cardiac side effects)
• Augmentation (specialist): Low-dose antipsychotic (risperidone 0.25-2mg, aripiprazole 5-15mg) added to SSRI
• Treatment duration: Continue for ≥12 months after remission; gradual tapering

Referral Criteria

• Moderate-severe OCD - secondary care for CBT with ERP and SSRI optimisation
• Treatment-resistant OCD (failed 2 SSRI trials + CBT) - specialist OCD service
• Severe functional impairment - specialist/inpatient OCD unit
• PANDAS - paediatric neurology/psychiatry

• CBT with ERP: 60-70% response rate; gains well-maintained with continued practice
• SSRIs: 40-60% response rate; high relapse rate on discontinuation (~50%)
• Combined CBT + SSRI: Best outcomes, especially for moderate-severe OCD
• Course: Chronic and relapsing in most cases; ~20% have a chronic unremitting course
• Predictors of poor outcome: Early onset, poor insight, hoarding symptoms, comorbid depression, family history
• Functional recovery: Even with symptom reduction, many patients have residual functional impairment

Y-BOCS Severity

NICE CG31 Stepped Care

Key Facts

PTSD is a trauma and stress-related disorder that develops following exposure to an exceptionally threatening or horrifying event. It causes significant psychological distress and functional impairment through four core symptom clusters.

Epidemiology

Lifetime prevalence in the UK is approximately 3-4%. Higher in military personnel (~6-17%), emergency service workers, and refugees. Women are approximately twice as likely to develop PTSD as men. Median time to treatment is 12 years.

Aetiology

• Traumatic events: Combat, assault, rape, accidents, natural disasters, terrorism, childhood abuse
• Risk factors: Female sex, prior psychiatric history, childhood adversity, peritraumatic dissociation, lack of social support, repeated trauma
• Protective factors: Social support, resilience, higher education, adaptive coping

Pathophysiology

• Fear conditioning: Amygdala hyperactivation - traumatic cues trigger exaggerated fear response
• Hippocampal dysfunction: Impaired contextualisation of memories - explains flashbacks (memories experienced as current events)
• Prefrontal cortex hypofunction: Failed top-down regulation of amygdala
• HPA axis dysregulation: Paradoxically LOW cortisol in PTSD (unlike depression) - enhanced negative feedback
• Noradrenergic hyperactivity: Locus coeruleus overactivity → hyperarousal, exaggerated startle
• Memory consolidation: Traumatic memories poorly integrated into autobiographical memory - remain "unprocessed" and intrusive

Re-experiencing

• Flashbacks: Vivid, involuntary reliving of the trauma (as if happening now)
• Nightmares: Distressing dreams of the event
• Intrusive memories: Unwanted, distressing recollections
• Psychological/physiological reactivity to trauma reminders

Avoidance

• Avoidance of thoughts, feelings, or conversations about the trauma
• Avoidance of people, places, activities that trigger memories

Negative Cognitions and Mood

• Persistent negative beliefs ("I am broken," "The world is dangerous")
• Distorted blame of self or others for the trauma
• Persistent negative emotional state (fear, horror, anger, guilt, shame)
• Diminished interest in activities, detachment from others

Hyperarousal

• Hypervigilance, exaggerated startle response
• Irritability, anger outbursts
• Difficulty concentrating
• Sleep disturbance
• Reckless or self-destructive behaviour

Red Flags

• Suicidal ideation - PTSD has significant suicide risk (~5-10× general population)
• Substance misuse - very common comorbidity (self-medication)
• Dissociative symptoms - depersonalisation/derealisation variant
• Complex PTSD - requires longer, phased treatment approach

Bedside

• PCL-5 (PTSD Checklist): 20-item self-report measure aligned with DSM-5
• IES-R (Impact of Event Scale-Revised): Screening tool
• PHQ-9, GAD-7: Comorbid depression and anxiety screening
• AUDIT-C: Alcohol misuse screening
• Risk assessment: Comprehensive - suicide, self-harm, violence

Bloods

• TFTs: Exclude thyroid dysfunction
• FBC, LFTs: Baseline and alcohol-related complications
• Drug screen: If substance misuse suspected

Special Tests

• Structured clinical interview: CAPS-5 (Clinician-Administered PTSD Scale) - gold standard diagnostic tool
• Neuroimaging: Not routine - research shows reduced hippocampal volume, amygdala hyperactivity

Non-pharmacological (NICE NG116)

• Active monitoring: For mild symptoms <4 weeks post-trauma - many improve spontaneously
• Trauma-focused CBT: First-line - 8-12 sessions; includes trauma narrative, cognitive restructuring, in-vivo exposure
• EMDR (Eye Movement Desensitisation and Reprocessing): First-line - 8-12 sessions; bilateral stimulation during trauma memory processing
• NOT recommended: Single-session psychological debriefing

Pharmacological (NICE NG116)

• Second-line (if psychological therapy declined, not available, or not effective):
  • Venlafaxine 75-150mg OD
  • SSRI: Sertraline 50-200mg OD or paroxetine 20-50mg OD
• Prazosin 1-15mg ON: For PTSD-related nightmares (alpha-1 blocker, off-label)
• Not recommended: Benzodiazepines (may worsen PTSD, impair extinction learning)
• Treatment duration: Continue for ≥12 months; gradual tapering

Referral Criteria

• PTSD symptoms >1 month - psychological therapy referral (IAPT or specialist trauma service)
• Complex PTSD - specialist trauma service
• Treatment-resistant PTSD - secondary care psychiatry
• Significant comorbidity - MDT approach
• Military veterans - Op COURAGE (NHS Veterans' Mental Health service)

• Natural course: ~50% recover within 3 months; ~30% have chronic course
• Trauma-focused CBT: ~60-70% response rate; gains well-maintained
• EMDR: Similar efficacy to trauma-focused CBT
• Chronic PTSD (>1 year): Poorer prognosis; may require longer treatment

• Comorbidity: ~80% have at least one comorbid condition (depression, anxiety, substance misuse)
• Suicide: PTSD increases suicide risk ~5-10×; comprehensive risk management essential

ICD-11 Complex PTSD

PTSD Risk Factors

Key Facts

Phobias are characterised by marked, disproportionate fear of a specific object or situation, leading to avoidance. Despite recognising the fear as excessive, patients are unable to control their anxiety response. Phobias are highly treatable with exposure-based psychological therapy.

Epidemiology

Specific phobias have a lifetime prevalence of 7-12% (most common mental health disorders). Agoraphobia affects approximately 1.7% of the population. Women are affected approximately twice as often as men. Onset is typically in childhood for specific phobias and adolescence/early adulthood for agoraphobia.

Aetiology

• Classical conditioning: Direct traumatic experience with the feared stimulus → learned fear association
• Observational learning: Witnessing others' fearful responses (vicarious conditioning)
• Information transmission: Being told about dangers (cognitive pathway)
• Prepared learning theory (Seligman): Evolutionary preparedness to develop fears of ancestral threats (snakes, heights, spiders) more readily
• Genetic: Heritability ~30-40%; blood-injection-injury phobia has the highest heritability (~60%)

Pathophysiology

• Amygdala hyperactivation: Excessive threat detection for phobic stimuli
• Deficient prefrontal regulation: Failed cognitive control over fear response
• Blood-injection-injury phobia: Unique biphasic response - initial sympathetic activation followed by parasympathetic (vagal) dominance → bradycardia and syncope
• Exposure therapy mechanism: Extinction learning - new inhibitory memory formed that competes with original fear association

Specific Phobia

• Marked fear disproportionate to actual danger
• Immediate anxiety response on encountering stimulus (or anticipation)
• Avoidance of feared stimulus or endured with intense distress
• Significant functional impairment or marked distress about having the phobia
• Persistent - typically ≥6 months

Agoraphobia

• Fear/anxiety about ≥2 of: Public transport, open spaces, enclosed spaces, standing in line/crowds, being outside the home alone
• Fear of not being able to escape or get help if panic-like symptoms develop
• Active avoidance → may become housebound in severe cases

Red Flags

• Housebound due to agoraphobia - urgent psychological therapy referral
• Blood-injection-injury phobia in healthcare worker - significant occupational impact
• Comorbid depression or substance misuse
• Phobia causing significant social or occupational dysfunction

Bedside

• Clinical interview: Identify specific phobia type, triggers, avoidance patterns, functional impact
• PHQ-9/GAD-7: Screen for comorbid depression and generalised anxiety
• Functional assessment: Impact on work, social life, daily activities

Bloods

• Generally not required unless differential diagnosis includes medical condition
• TFTs: If anxiety symptoms suggest thyroid dysfunction

Special Tests

• Behavioural avoidance test (BAT): Standardised approach to phobic stimulus to assess severity
• Subjective Units of Distress Scale (SUDS): Self-rated 0-100 during exposure hierarchy

Non-pharmacological (First-line - NICE CG159)

• CBT with graded exposure (systematic desensitisation):
  • Construct fear hierarchy (SUDS ratings)
  • Graded exposure: Start with least anxiety-provoking situation, progress gradually
  • In-vivo exposure is more effective than imaginal exposure
  • Typically 5-10 sessions
• Applied tension technique (Öst): Specific to blood-injection-injury phobia - tense large muscle groups to maintain BP during blood exposure
• Virtual reality exposure therapy: Emerging evidence - effective for fear of heights, flying, spiders

Pharmacological

• Generally not first-line for specific phobias - CBT is preferred
• SSRI (sertraline, paroxetine): May be used for agoraphobia, especially with comorbid panic
• Propranolol 10-40mg PRN: For performance anxiety or specific situational phobias (e.g., flying)
• Benzodiazepines: Short-term for specific situations (e.g., diazepam 2-5mg before dental procedure) - does not produce lasting improvement

Referral Criteria

• Phobia causing significant functional impairment - IAPT (Improving Access to Psychological Therapies)
• Severe agoraphobia - specialist anxiety service
• Comorbid conditions requiring complex management

• Specific phobias: Very treatable - CBT with exposure has 80-90% response rate in many studies
• Single-session exposure therapy can be effective for some specific phobias (Öst model)
• Agoraphobia: More chronic course; ~30-40% remit without treatment; CBT improves outcomes significantly
• Without treatment: Specific phobias tend to persist - only ~20% spontaneously remit in adulthood
• Blood-injection-injury phobia: Applied tension technique highly effective (>90% improvement)
• Comorbid depression worsens prognosis for all phobia subtypes

Specific Phobia Subtypes

Exposure Therapy Principles

Key Facts

Social anxiety disorder (SAD) is characterised by excessive fear and avoidance of social situations due to concerns about being negatively evaluated. It typically begins in adolescence and has a chronic course if untreated.

Epidemiology

Lifetime prevalence is 7-12%, making it one of the most common mental health conditions. Median age of onset is 13 years. Without treatment, the mean duration is approximately 20 years. Slightly more common in women. Only ~5% of sufferers seek treatment within the first year of onset.

Aetiology

• Genetic: Heritability ~30%; behavioural inhibition in childhood is a key temperamental risk factor
• Neurobiological: Amygdala hyperactivation to social stimuli; reduced serotonergic transmission
• Psychological: Clark and Wells (1995) cognitive model - self-focused attention, safety behaviours, post-event rumination
• Environmental: Bullying, social rejection, overprotective/controlling parenting, modelling of social anxiety by parents

Pathophysiology

Clark and Wells cognitive model:

1. Social situation triggers negative automatic thoughts ("They'll think I'm stupid")
2. Self-focused attention - internal monitoring of anxiety symptoms
3. Safety behaviours - avoid eye contact, rehearse what to say, grip glass tightly (maintain beliefs)
4. Post-event rumination - dwelling on perceived failures after the event
5. Distorted self-image - exaggerated view of how anxious they appeared to others

This creates a vicious cycle that maintains the disorder and prevents natural disconfirmation of feared outcomes.

Core Features

• Marked fear or anxiety in social situations where scrutinised by others
• Situations include: Conversations, meeting unfamiliar people, eating/drinking in public, performing/speaking in front of others
• Fear of showing anxiety symptoms that will be negatively evaluated (blushing, trembling, sweating, stumbling over words)
• Avoidance of social situations or endured with intense anxiety
• Persistent - ≥6 months
• Functionally impairing: Significant impact on work, education, relationships

Associated Features

• Blushing, trembling, sweating, dry mouth, tachycardia
• Difficulty making eye contact
• Low self-esteem, self-criticism
• Alcohol/substance misuse as self-medication

Red Flags

• Severe avoidance leading to inability to work or attend education
• Comorbid depression with suicidal ideation
• Heavy alcohol use to cope - dependence risk
• Childhood onset without improvement - chronic functional impairment

Bedside

• LSAS (Liebowitz Social Anxiety Scale): 24 items - fear and avoidance ratings
• SPIN (Social Phobia Inventory): 17-item self-report
• PHQ-9, GAD-7: Comorbid depression and anxiety
• AUDIT-C: Alcohol screening
• Functional assessment: Impact on work, education, relationships

Bloods

• TFTs: If anxiety symptoms prominent - exclude thyroid dysfunction
• FBC: Baseline if starting medication

Special Tests

• Generally not required - diagnosis is clinical
• Structured clinical interview (SCID) for research/diagnostic certainty

Non-pharmacological (NICE CG159)

• First-line: Individual CBT based on Clark and Wells or Heimberg model (14-16 sessions)
  • Identify and test negative predictions through behavioural experiments
  • Shift from self-focused to externally-focused attention
  • Drop safety behaviours
  • Address post-event rumination
  • Video feedback to correct distorted self-image
• NOT recommended: Group CBT as first-line (individual CBT is superior for SAD)
• Psychoeducation groups, guided self-help as lower-intensity options

Pharmacological

• First-line: Escitalopram 10-20mg OD or sertraline 50-200mg OD
• Second-line: Venlafaxine 75-225mg OD (SNRI)
• Performance anxiety only: Propranolol 10-40mg PRN 30-60 minutes before event
• Not recommended: Benzodiazepines (dependence risk), MAOIs (dietary restrictions)
• Duration: Continue for ≥12 months after remission

Referral Criteria

• Social anxiety causing significant functional impairment - IAPT referral
• Treatment-resistant (failed CBT + SSRI) - specialist anxiety service
• Severe comorbidity - secondary care psychiatry
• Suspected ASD - neurodevelopmental assessment

• Without treatment: Chronic course - mean duration ~20 years; spontaneous remission rate low (~20-30%)
• Individual CBT (Clark model): ~75% response rate; very well-maintained at follow-up
• SSRIs: ~50-60% response rate; significant relapse on discontinuation
• Combined CBT + SSRI: May be beneficial for severe cases
• Performance-only subtype: Better prognosis; may respond to brief intervention + beta-blocker
• Comorbidity: Depression (~50%), alcohol misuse (~25%), other anxiety disorders - worsen prognosis
• Early onset and long duration before treatment predict poorer response

Clark and Wells Model of Social Anxiety

Social Anxiety vs Avoidant Personality Disorder

Key Facts

Schizophrenia is a severe, chronic mental illness characterised by psychotic symptoms, negative symptoms, and cognitive dysfunction. It typically presents in late adolescence or early adulthood and requires lifelong treatment.

Epidemiology

Lifetime prevalence is approximately 1% worldwide. Annual incidence is ~15-20 per 100,000. Males have earlier onset (18-25) than females (25-35). Schizophrenia reduces life expectancy by 15-20 years primarily due to cardiovascular disease, suicide, and metabolic syndrome.

Aetiology

• Genetic: Heritability ~80%; monozygotic twin concordance ~48%; polygenic - >100 associated loci
• Neurodevelopmental: Obstetric complications, prenatal infection, childhood adversity
• Neurochemical: Dopamine dysregulation, glutamate (NMDA receptor hypofunction), serotonergic involvement
• Environmental: Cannabis (especially adolescent use of high-potency), urban upbringing, migration, social adversity
• Neurodevelopmental hypothesis: Schizophrenia as a disorder of abnormal brain development, with genetic and environmental risk factors converging

Pathophysiology

• Glutamate hypothesis: NMDA receptor hypofunction → downstream dopamine dysregulation (supported by PCP/ketamine models)
• Structural changes: Enlarged lateral ventricles, reduced cortical grey matter, reduced hippocampal volume
• Synaptic pruning: Excessive synaptic pruning in adolescence (complement C4 gene association) may contribute to symptom onset

Positive Symptoms

• Delusions: Persecutory, grandiose, referential, nihilistic, erotomanic, somatic; bizarre delusions (culturally implausible)
• Hallucinations: Auditory most common (voices - third person, running commentary, thought echo); visual, olfactory, tactile possible
• Thought disorder: Tangentiality, circumstantiality, loosening of associations, word salad, neologisms, thought blocking
• Passivity phenomena: Thought insertion, withdrawal, broadcast; made actions/feelings/impulses

Negative Symptoms

• Flat or blunted affect
• Alogia (poverty of speech)
• Avolition (loss of motivation)
• Anhedonia (loss of pleasure)
• Social withdrawal

Cognitive Symptoms

• Impaired working memory, attention, processing speed
• Executive dysfunction
• Often present before psychotic symptoms and persist after positive symptoms treated

Red Flags

• First-episode psychosis in young person - urgent assessment (early intervention in psychosis team)
• Command hallucinations to harm self/others - immediate risk assessment
• Catatonia - medical emergency; consider benzodiazepines, ECT
• Neuroleptic malignant syndrome on antipsychotics - pyrexia, rigidity, altered consciousness, raised CK

Bedside

• Mental state examination (MSE): Comprehensive assessment of appearance, behaviour, speech, mood, thought form/content, perception, cognition, insight
• Risk assessment: Suicide (5-10% lifetime risk), violence, self-neglect, vulnerability
• Cognitive assessment: Brief cognitive screen (MoCA, MMSE)
• Collateral history: Essential - from family, friends, GP

Bloods

• FBC: Baseline for antipsychotic monitoring; WCC for clozapine
• U&Es, LFTs: Baseline renal and liver function
• TFTs: Exclude thyroid dysfunction
• Fasting glucose, HbA1c, lipid profile: Metabolic syndrome baseline (antipsychotics cause weight gain and metabolic disturbance)
• Prolactin: Baseline and if symptoms suggest hyperprolactinaemia (antipsychotic side effect)
• Urine drug screen: Exclude substance-induced psychosis

Imaging

• MRI brain: Consider in first episode to exclude organic cause (tumour, demyelination)
• CT head: If MRI unavailable or acutely indicated

Special Tests

• ECG: QTc baseline before antipsychotics (many prolong QT)
• EEG: If seizures or encephalitis suspected
• NMDA receptor antibody testing: If suspected autoimmune encephalitis (especially young women with psychosis + movement disorder)

Non-pharmacological

• Early Intervention in Psychosis (EIP) team: All first-episode psychosis - NICE mandated within 2 weeks
• CBT for psychosis (CBTp): At least 16 sessions for all patients
• Family intervention: Reduces relapse rate by ~50%; 10+ sessions over 3-12 months
• Supported employment: Individual Placement and Support (IPS) model
• Arts therapies: Particularly for negative symptoms

Pharmacological (NICE CG178)

First-episode psychosis:

• Oral atypical antipsychotic: Risperidone 2-6mg OD, olanzapine 10-20mg OD, aripiprazole 10-30mg OD, or quetiapine 300-750mg/day
• Discuss efficacy, side effect profile with patient - shared decision-making
• Trial for 4-6 weeks at therapeutic dose before switching

Treatment-resistant schizophrenia (failed ≥2 antipsychotics):

• Clozapine: Start 12.5mg OD, titrate slowly to 300-450mg/day (max 900mg)

• Side effects: Agranulocytosis (~1%), metabolic syndrome, sedation, constipation (can be fatal), myocarditis (~1-3%), seizures

Long-acting injectable antipsychotics (LAI):

• Paliperidone palmitate, aripiprazole lauroxil, flupentixol decanoate - if oral adherence poor

Referral Criteria

• Suspected first-episode psychosis - urgent EIP team referral (within 2 weeks)
• Treatment-resistant schizophrenia - clozapine initiation (specialist)
• Forensic risk - forensic psychiatry
• Catatonia - emergency psychiatric assessment

• Rule of thirds: ~1/3 good outcome, ~1/3 intermediate, ~1/3 chronic/severe course (simplified)
• Life expectancy: Reduced by 15-20 years vs general population
• Suicide: Lifetime risk 5-10%; highest risk in first 5 years and following discharge
• Relapse: ~80% relapse within 5 years if antipsychotic discontinued; ~20% on medication
• Clozapine: Response rate 30-60% in treatment-resistant cases; also reduces suicidality
• Good prognostic factors: Late onset, female sex, acute onset, good premorbid function, affective symptoms, family history of mood disorder, adherence to treatment
• Poor prognostic factors: Early onset, male sex, insidious onset, social isolation, prominent negative symptoms, substance misuse, family history of schizophrenia

Antipsychotic Side Effect Comparison

Dopamine Pathways

Key Facts

Schizoaffective disorder occupies a diagnostic position between schizophrenia and mood disorders. The key distinguishing feature is that psychotic symptoms must be present both during and outside of mood episodes.

Epidemiology

Lifetime prevalence is approximately 0.3%. Slightly more common in women. Age of onset is similar to schizophrenia (late teens to early 30s). Bipolar type may be more common in younger patients.

Aetiology

• Genetic: Shared genetic risk factors with both schizophrenia and bipolar disorder; family studies show increased rates of both conditions in relatives
• Neurochemical: Combined dopaminergic and serotonergic dysregulation
• Neurodevelopmental: Some evidence of intermediate neurodevelopmental abnormalities between schizophrenia and bipolar disorder
• Environmental: Similar risk factors to schizophrenia (substance use, social adversity)

Pathophysiology

• Shares neurobiological features with both schizophrenia and bipolar disorder
• Intermediate brain structural changes - more grey matter loss than bipolar but less than schizophrenia
• Combined dopamine (psychosis) and monoamine (mood) dysregulation
• Some researchers question whether it is a distinct entity or a spectrum between schizophrenia and bipolar disorder

Bipolar Type

• Episodes of mania with concurrent psychotic symptoms
• Depressive episodes may also occur
• Psychotic symptoms persist even when mood normalises

Depressive Type

• Depressive episodes with concurrent psychotic symptoms
• No manic episodes
• Psychotic symptoms persist during euthymic periods

Key Diagnostic Requirement

• Period of at least 2 weeks with delusions/hallucinations in the absence of prominent mood symptoms (distinguishes from bipolar disorder with psychotic features)

Red Flags

• Suicide risk - similar to bipolar disorder (~5-10% lifetime)
• Substance misuse - common comorbidity
• Non-adherence to complex medication regimen
• Treatment-resistant psychotic symptoms - consider clozapine

Bedside

• MSE: Comprehensive mental state examination
• Mood charting: Longitudinal documentation of mood episodes and psychotic symptoms
• Risk assessment: Suicide, self-harm, risk to others
• Collateral history: Timeline of mood vs psychotic symptoms

Bloods

• FBC, U&Es, LFTs, TFTs: Baseline and medication monitoring
• Fasting glucose, lipids, HbA1c: Metabolic monitoring
• Lithium level: If on lithium (target 0.6-0.8 mmol/L)
• Urine drug screen: Exclude substance-induced presentation

Special Tests

• ECG: QTc baseline for antipsychotics
• MRI brain: First presentation to exclude organic cause
• Prolactin: If symptoms of hyperprolactinaemia

Non-pharmacological

• Psychoeducation: Understanding the dual nature of the illness
• CBT for psychosis: As per schizophrenia guidelines
• Family intervention: Reduces relapse
• Social support: Supported accommodation, employment support
• Relapse prevention planning: Identify early warning signs for both mood and psychotic episodes

Pharmacological

Bipolar type:

• Antipsychotic (risperidone, olanzapine, quetiapine) + mood stabiliser (lithium or valproate)
• Lithium: 400-1200mg daily, target 0.6-0.8 mmol/L

Depressive type:

• Antipsychotic + antidepressant (SSRI) - caution with antidepressant monotherapy (may worsen psychosis)
• Lamotrigine may be useful for depressive symptoms

Treatment-resistant:

• Clozapine - as per schizophrenia guidelines
• ECT - may be effective for both mood and psychotic components

Referral Criteria

• All patients - secondary care psychiatry for diagnosis confirmation and treatment initiation
• Treatment-resistant - specialist services, clozapine consideration
• Acute relapse with risk - crisis team or inpatient admission

• Intermediate prognosis: Better than schizophrenia, worse than bipolar disorder
• Bipolar type generally has a better outcome than depressive type
• Suicide risk: Approximately 5-10% lifetime
• Functional outcome: Better than schizophrenia; many achieve reasonable social and occupational functioning with treatment
• Relapse: High if medication discontinued - long-term treatment recommended
• Mortality: Reduced life expectancy due to cardiovascular disease, metabolic syndrome, and suicide

Distinguishing Key Diagnoses

Treatment Summary

Key Facts

Delusional disorder involves fixed, systematised, non-bizarre delusions without the broader psychotic features of schizophrenia. Behaviour outside the delusional system is not markedly bizarre.

Epidemiology

Lifetime prevalence is approximately 0.02-0.03%. Mean onset is 40-50 years, later than schizophrenia. Persecutory subtype accounts for ~50% of cases. Slight female predominance.

Aetiology

• Neurobiological: Dopaminergic dysfunction in limbic system, though less pronounced than schizophrenia
• Psychological: Attribution biases, jumping-to-conclusions reasoning, social isolation, sensory impairment (hearing/vision loss in elderly)
• Genetic: Some familial association with schizophrenia spectrum disorders
• Social: Immigration, social adversity, loneliness

Pathophysiology

• Abnormal salience attribution - brain assigns excessive significance to neutral stimuli
• Jumping-to-conclusions bias - less evidence required before forming beliefs
• Theory of mind deficits may promote paranoid ideation
• Minimal structural brain changes compared to schizophrenia

Subtypes

• Persecutory: Being conspired against, followed, poisoned (most common)
• Erotomanic: Another person (usually higher status) is in love with the patient
• Grandiose: Exceptional talent, power, or special relationship
• Jealous (Othello syndrome): Unfounded conviction of partner's infidelity
• Somatic: Body function abnormality (emitting odour, parasites, deformity)

Key Clinical Features

• Delusions are systematised and logically developed
• Affect appropriate to delusional content
• No prominent hallucinations, thought disorder, or negative symptoms
• Relatively preserved functioning outside delusional system

Red Flags

• Jealous type with aggression towards partner - significant violence risk
• Persecutory delusions with retaliation plans - forensic risk
• Erotomania with stalking behaviour - legal and safety implications
• Somatic type with repeated inappropriate medical/surgical consultations

Bedside

• MSE: Delusional content, systematisation, insight assessment
• Risk assessment: Particularly jealous and persecutory types
• Collateral history: Patient may present convincing narrative

Bloods

• TFTs, FBC, U&Es, LFTs, calcium, B12: Exclude organic causes
• Urine drug screen: Exclude substance-induced psychosis

Special Tests

• MRI brain: Consider in late-onset presentations
• Audiometry/vision testing: Sensory impairment as contributing factor
• Cognitive assessment: Exclude dementia in elderly

Non-pharmacological

• Build therapeutic alliance without colluding with or directly challenging delusion
• CBT: Guided discovery to examine evidence for/against beliefs
• Social interventions to address isolation

Pharmacological

• Antipsychotics (often partially effective; patients frequently reluctant):
  • Risperidone 1-4mg OD or olanzapine 5-15mg OD
  • Lower doses than schizophrenia may suffice
  • Trial ≥6-8 weeks at adequate dose
• SSRIs: If comorbid depression or somatic subtype
• Managed under NICE CG178 (psychosis and schizophrenia)

Referral Criteria

• All suspected cases - psychiatric assessment
• Jealous type with partner at risk - urgent safeguarding
• Stalking behaviour - forensic psychiatry
• Failed outpatient treatment - inpatient assessment

• Chronic course: ~50% persistent delusions; ~20% full remission; ~30% partial remission
• Better prognosis: Female sex, acute onset, shorter duration, non-paranoid subtype
• Jealous type: One of the most dangerous psychiatric presentations - significant partner violence risk
• Functional outcome: Generally better than schizophrenia
• Treatment engagement: Poor - many patients lack insight

Delusional Disorder vs Schizophrenia

Key Facts

Brief psychotic disorder is characterised by sudden onset of psychotic symptoms lasting 1 day to 1 month with complete return to premorbid functioning.

Epidemiology

Relatively uncommon; accounts for approximately 2-7% of first-episode psychoses. More common in women and in developing countries. Peak onset late 20s to 30s.

Aetiology

• Psychosocial stressors: Bereavement, relationship breakdown, trauma, immigration
• Personality vulnerability: Pre-existing borderline or schizotypal traits
• Postpartum: Can occur in the postpartum period
• Neurobiological: Transient dopaminergic dysregulation

Pathophysiology

• Transient stress-induced dopaminergic dysregulation in vulnerable individuals
• HPA axis hyperactivation may trigger psychotic symptoms
• Complete resolution suggests intact underlying brain structure
• May represent threshold phenomenon - extreme stress exceeding coping capacity

Presentation

• Sudden onset (within 2 weeks of normal functioning)
• Delusions, hallucinations, disorganised speech/behaviour
• Emotional turmoil - rapid mood shifts, confusion, perplexity
• Significant distress and bewilderment

Course

• Complete resolution within 1 month
• Return to full premorbid functioning
• No residual negative symptoms

Red Flags

• Symptoms persisting >1 month - reassess diagnosis
• Suicide risk during acute episode - monitor closely
• Postpartum onset - consider puerperal psychosis
• Substance use - exclude substance-induced psychosis

Bedside

• MSE: Full mental state examination
• Risk assessment: Suicide and self-harm risk
• Collateral history: Premorbid functioning, stressor, timeline

Bloods

• FBC, U&Es, LFTs, TFTs, CRP, calcium, glucose, B12: Exclude organic causes
• Urine drug screen: Essential

Special Tests

• CT/MRI brain: Consider if atypical features
• ECG: Baseline if antipsychotic initiated

Non-pharmacological

• Supportive, low-stimulation environment
• Psychoeducation for patient and family
• Short-term crisis team involvement

Pharmacological

• Short-term antipsychotic: Risperidone 1-2mg or olanzapine 5-10mg
• Benzodiazepine: Lorazepam 1-2mg for acute agitation
• Taper and discontinue antipsychotic once symptoms resolve (1-3 months)
• Longer-term prophylaxis if recurrent episodes

Referral Criteria

• All first-episode psychosis - EIP team assessment
• Postpartum onset - perinatal mental health team
• Symptoms beyond 1 month - reassess diagnosis

• Good prognosis by definition - full recovery within 1 month
• ~50% have further psychotic episodes
• 20-50% eventually diagnosed with schizophrenia or bipolar disorder
• Good premorbid functioning and identifiable stressor predict better outcome
• Risk factors for recurrence: Family history of psychosis, substance misuse, personality vulnerability

Duration-Based Classification

Key Facts

FEP is a critical period where early comprehensive intervention has the greatest impact on long-term outcomes. NHS mandates access to EIP services for all cases.

Epidemiology

Incidence approximately 32 per 100,000/year in the UK. Peak onset 18-24 years. Males have earlier onset. Significant health inequalities - Black Caribbean and Black African populations have 5-10× higher rates.

Aetiology

Pathophysiology

• Prodromal phase (1-5 years before FEP): Progressive neurobiological change before threshold symptoms
• Critical period hypothesis: First 2-5 years after FEP are a window of neuroplasticity where intervention has maximal impact
• Mesolimbic dopamine overactivity drives positive symptoms
• Excessive synaptic pruning in adolescence may contribute (C4 gene association)

Prodromal Features

• Declining academic/occupational performance
• Social withdrawal, suspiciousness, irritability
• Unusual/magical thinking, sub-threshold psychotic experiences
• Sleep disturbance, reduced motivation

Psychotic Episode

• Positive symptoms: Delusions, hallucinations, thought disorder
• Behavioural change: Bizarre behaviour, agitation, self-neglect
• Cognitive decline, negative symptoms may be present from outset

Red Flags

• Organic features (confusion, visual hallucinations, seizures, focal neurology) - investigate urgently
• Catatonia (immobility, mutism, posturing) - medical emergency
• High suicide risk: ~5% die by suicide within first 5 years
• Command hallucinations to harm self/others

Bedside

• Full MSE and neurological examination
• Risk assessment: Suicide, violence, self-neglect, vulnerability
• Collateral history: Essential

Bloods

• FBC, U&Es, LFTs, TFTs, fasting glucose, HbA1c, lipids: Baseline and organic screen
• Calcium, B12, folate, CRP: Metabolic/inflammatory causes
• HIV, syphilis serology: Infective causes
• Urine drug screen: Cannabis, amphetamines, cocaine
• NMDA receptor antibodies: If encephalitis suspected

Imaging

• MRI brain: Recommended in all FEP to exclude organic pathology

Special Tests

• ECG: Baseline before antipsychotic
• EEG: If seizures suspected
• Neuropsychological assessment: Baseline cognitive profile

Non-pharmacological

• EIP team: Comprehensive care package for 3 years
• CBTp: ≥16 sessions
• Family intervention: ≥10 sessions - reduces relapse by ~50%
• Supported employment/education: IPS model
• Physical health monitoring: Annual metabolic screening

Pharmacological

• Low-dose atypical antipsychotic: Aripiprazole 5-15mg, risperidone 1-4mg, or olanzapine 5-15mg
• Start lowest dose, titrate slowly; trial 4-6 weeks before switching
• Continue ≥1-2 years after FEP
• Clozapine if failed 2 adequate trials

Referral Criteria

• All suspected FEP - EIP team within 2 weeks (NHS standard)
• Organic features - neurology
• Under 14 - CAMHS
• Postpartum psychosis - perinatal team

• ~25% single episode with full recovery
• ~50% relapsing-remitting course
• ~25% chronic, treatment-resistant illness
• DUP >3 months associated with significantly worse outcomes
• Suicide: ~5% in first 5 years
• EIP services reduce hospitalisation by 50% and improve employment
• Cannabis cessation after FEP significantly improves outcomes

EIP Core Components (NICE CG178)

Key Facts

Personality disorders represent enduring patterns of cognition, affectivity, interpersonal functioning, and impulse control that are inflexible, pervasive, and lead to clinically significant distress or functional impairment.

Epidemiology

Prevalence in the general population is 4-13%. Personality disorders are present in 40-70% of psychiatric inpatients. BPD is the most commonly encountered in clinical settings (~2% prevalence). Antisocial PD affects ~3% of men and ~1% of women.

Aetiology

• Genetic: Heritability ~40-60%; strongest for antisocial and borderline PD
• Childhood adversity: Abuse, neglect, inconsistent parenting - strong association with BPD
• Attachment: Insecure attachment patterns, especially disorganised attachment
• Neurodevelopmental: Temperamental traits (high negative emotionality, low effortful control)

Pathophysiology

• BPD: Amygdala hyperreactivity, prefrontal cortex hypofunction, impaired mentalisation
• ASPD: Reduced amygdala and prefrontal cortex activation during moral decision-making; reduced autonomic reactivity
• Dimensional model (ICD-11): Personality functioning assessed on a spectrum of severity rather than categorical diagnoses
• Personality disorders represent the extreme end of normal personality trait distributions

Cluster A (Odd/Eccentric)

• Paranoid: Pervasive distrust, suspiciousness, misinterpretation of motives
• Schizoid: Detachment from social relationships, restricted emotional range
• Schizotypal: Cognitive/perceptual distortions, eccentric behaviour, social anxiety

Cluster B (Dramatic/Emotional)

• Borderline (EUPD): Emotional instability, impulsivity, unstable relationships, identity disturbance, self-harm, chronic emptiness, fear of abandonment
• Antisocial: Disregard for rights of others, impulsivity, deceitfulness, lack of remorse, conduct disorder before age 15
• Histrionic: Excessive emotionality, attention-seeking, suggestibility
• Narcissistic: Grandiosity, need for admiration, lack of empathy

Cluster C (Anxious/Fearful)

• Avoidant: Social inhibition, feelings of inadequacy, hypersensitivity to criticism
• Dependent: Excessive need for care, submissive behaviour, fear of separation
• Anankastic (OCPD): Preoccupation with orderliness, perfectionism, control (ego-syntonic, unlike OCD)

Red Flags

• Active self-harm or suicidal ideation - comprehensive risk assessment
• Forensic risk in antisocial PD - violence risk assessment
• Comorbid substance misuse - worsens outcomes significantly
• Personality disorder diagnosis in under-18s - use with extreme caution

Bedside

• Structured clinical assessment: Detailed personal history, relationship patterns, occupational history
• Self-report measures: PID-5 (Personality Inventory for DSM-5), SAPAS (Standardised Assessment of Personality - Abbreviated Scale)
• Risk assessment: Self-harm, suicide, violence
• Collateral history: Important for corroboration

Bloods

• TFTs, FBC, LFTs: Exclude organic causes of personality change
• Urine drug screen: Comorbid substance misuse

Special Tests

• Structured Clinical Interview for DSM-5 PD (SCID-5-PD): Gold standard research tool
• IPDE (International Personality Disorder Examination): Standardised interview
• Cognitive assessment: If neurodevelopmental condition suspected

Non-pharmacological

• BPD (NICE CG78):
  • Structured clinical management (SCM): Integrated approach combining case management with psychological therapy
  • Mentalisation-based treatment (MBT): 18 months; improves reflective functioning
  • Dialectical behaviour therapy (DBT): Skills training (mindfulness, distress tolerance, emotion regulation, interpersonal effectiveness)
  • Schema-focused therapy: Identifies early maladaptive schemas
• ASPD (NICE CG77): Group-based cognitive-behavioural programmes; therapeutic communities
• All PDs: Crisis planning, continuity of care, therapeutic relationship as key mechanism

Pharmacological

• No medication is licensed for personality disorders
• Short-term symptom management only:
  • SSRIs for comorbid depression/anxiety
  • Low-dose antipsychotics for transient psychotic symptoms or severe agitation (very short-term)
  • Avoid benzodiazepines - dependence risk, disinhibition
  • Avoid polypharmacy - review and rationalise

Referral Criteria

• BPD with recurrent self-harm - specialist personality disorder service
• ASPD with forensic risk - forensic psychiatry
• Complex comorbidity - specialist mental health team
• Consider neurodevelopmental assessment if ADHD/ASD suspected

• BPD: Improves with age - ~85% no longer meet diagnostic criteria by age 40-50; however functional recovery lags behind symptomatic improvement
• ASPD: Tends to attenuate with age, particularly impulsivity; but psychopathic traits persist
• Suicide: BPD lifetime suicide rate approximately 8-10%; highest risk in young adults
• Comorbidity: High rates of depression (75%), substance misuse (50-70%), anxiety disorders, eating disorders
• DBT: Reduces self-harm by ~50% compared to treatment as usual
• MBT: Significant improvements in interpersonal functioning, maintained at 8-year follow-up

ICD-11 Personality Disorder Model

Trait Qualifiers (ICD-11)

Key Facts

BPD is one of the most commonly encountered personality disorders in clinical practice. It is characterised by pervasive instability in emotions, relationships, self-image, and behaviour.

Epidemiology

General population prevalence 1-2%; up to 20% of psychiatric inpatients. In clinical settings, F:M ratio is 3:1. Mean age of presentation typically early 20s. Strong association with childhood adversity.

Aetiology

• Biosocial model (Linehan): Biological emotional vulnerability + invalidating environment → emotional dysregulation
• Childhood adversity: ~70% report abuse (sexual, physical, emotional) or neglect
• Genetic: Heritability ~40%; traits of emotional reactivity and impulsivity are heritable
• Attachment: Disorganised attachment pattern strongly associated
• Neurobiology: Amygdala hyperreactivity, reduced prefrontal cortex volume, altered serotonergic function

Pathophysiology

• Amygdala hyperactivation: Heightened emotional reactivity, threat perception
• Prefrontal cortex hypofunction: Impaired emotional regulation, impulse control
• Mentalisation deficits: Difficulty understanding own and others' mental states (Fonagy & Bateman)
• Schema activation: Early maladaptive schemas (abandonment, mistrust, defectiveness) drive interpersonal patterns

DSM-5 Criteria (≥5 of 9)

1. Frantic efforts to avoid real or imagined abandonment
2. Pattern of unstable, intense relationships (idealisation/devaluation)
3. Identity disturbance: Unstable self-image
4. Impulsivity in ≥2 areas (spending, sex, substances, reckless driving, binge eating)
5. Recurrent self-harm or suicidal behaviour
6. Affective instability: Intense, reactive mood lasting hours (rarely days)
7. Chronic feelings of emptiness
8. Inappropriate, intense anger
9. Transient stress-related paranoid ideation or dissociative symptoms

Red Flags

• Active self-harm with increasing lethality of methods
• Suicidal ideation with plan and intent
• Substance misuse escalation
• Psychotic symptoms (usually transient, stress-related)
• Severe functional decline

Bedside

• Detailed clinical assessment: Personal history, relationship patterns, trauma history
• Risk assessment: Self-harm history (methods, frequency, lethality), suicide risk, violence
• PHQ-9, GAD-7: Comorbid depression and anxiety screening
• AUDIT-C: Alcohol screening

Bloods

• TFTs: Exclude thyroid dysfunction
• FBC, LFTs: Baseline; alcohol effects
• Urine drug screen: Comorbid substance misuse

Special Tests

• ZAN-BPD: Zanarini Rating Scale for BPD - measures severity
• BSL-23: Borderline Symptom List - self-report outcome measure
• Cognitive assessment: If ADHD/ASD suspected as comorbid/differential

Non-pharmacological (NICE CG78 - first-line)

• DBT (Dialectical Behaviour Therapy): Weekly individual + group skills training (mindfulness, distress tolerance, emotion regulation, interpersonal effectiveness); 12+ months
• MBT (Mentalisation-Based Treatment): Individual + group therapy; improves reflective functioning; 18 months
• SCM (Structured Clinical Management): Case management with psychologically-informed approach
• Crisis planning: Written plan with patient, shared with GP and emergency services
• NOT recommended: Brief, unstructured psychological interventions; frequent changes of clinician

Pharmacological

• NICE CG78: Medication should NOT be used for core BPD symptoms
• Short-term only (≤1 week) for crisis:
  • Low-dose antipsychotic (quetiapine 25-100mg) or sedative antihistamine
  • Avoid benzodiazepines (dependence, disinhibition, overdose risk)
• Treat comorbid conditions (depression, anxiety) on their own merits
• Polypharmacy is a major problem - regular medication review and rationalisation

Referral Criteria

• Recurrent self-harm - specialist personality disorder service
• Need for structured psychological therapy (DBT, MBT) - secondary/tertiary care
• Crisis presentation - crisis team (avoid unnecessary admission where possible)
• Complex comorbidity - MDT approach

• Symptomatic improvement: ~85% no longer meet diagnostic criteria by age 40-50
• Functional recovery lags behind symptomatic improvement - many continue to have social/occupational difficulties
• Suicide: Lifetime rate 8-10%; highest risk in young adults in first years of treatment contact
• Self-harm: ~75% engage; ~10% ultimately die by suicide
• DBT: Reduces self-harm by ~50%, reduces hospitalisation
• MBT: Sustained improvements at 8-year follow-up
• Comorbidity: Depression (75%), substance misuse (50-70%), anxiety (50%), eating disorders (25%)

Linehan's Biosocial Model

BPD Defence Mechanisms

Key Facts

ASPD is characterised by a pervasive pattern of disregard for and violation of the rights of others. It is strongly associated with criminal behaviour, substance misuse, and violence.

Epidemiology

Prevalence ~3% in men, ~1% in women. Up to 50-80% of prison populations meet criteria. Strong association with socioeconomic deprivation, substance misuse, and childhood adversity.

Aetiology

• Genetic: Heritability ~50%; callous-unemotional traits are highly heritable
• Environmental: Childhood abuse/neglect, inconsistent parenting, peer influences, poverty
• Neurodevelopmental: Conduct disorder in childhood (essential prerequisite for diagnosis)
• Neurobiology: Reduced amygdala and prefrontal cortex activation; reduced autonomic arousal (fearlessness theory)

Pathophysiology

• Reduced amygdala function: Impaired fear conditioning, empathy, and moral reasoning
• Prefrontal cortex dysfunction: Poor impulse control, decision-making, and behavioural regulation
• Low cortisol: Reduced stress reactivity - may explain sensation-seeking and risk-taking
• Reduced autonomic arousal: Low resting heart rate in childhood predicts antisocial behaviour

Core Features

• Persistent disregard for social norms and the law
• Deceitfulness - repeated lying, conning for personal gain
• Impulsivity, failure to plan ahead
• Irritability and aggressiveness - repeated fights or assaults
• Reckless disregard for safety of self and others
• Consistent irresponsibility (work, financial)
• Lack of remorse - indifferent or rationalises harm to others

Diagnostic Requirements

• Age ≥18 years
• Evidence of conduct disorder before age 15
• Pattern not explained by schizophrenia or bipolar disorder

Red Flags

• Domestic violence perpetration - safeguarding concern
• Substance misuse with violent behaviour
• Fire-setting or sexual offending - forensic risk
• Macdonald triad in childhood (enuresis, fire-setting, animal cruelty) - historical predictors

Bedside

• Detailed clinical assessment: Full personal, forensic, and developmental history
• Risk assessment: Violence (HCR-20), sexual violence (Risk Matrix 2000), domestic abuse
• Collateral history: Essential - from probation, family, medical records
• AUDIT/DAST: Substance misuse screening

Bloods

• FBC, LFTs: Alcohol effects, baseline
• Urine drug screen: Substance misuse
• TFTs: Exclude organic personality change

Special Tests

• PCL-R (Psychopathy Checklist-Revised): 20-item assessment; ≥30/40 indicates psychopathy - use by trained professionals only
• HCR-20: Structured professional judgment for violence risk

Non-pharmacological (NICE CG77)

• Group-based cognitive-behavioural programmes: Focus on problem-solving, social skills, anger management
• Therapeutic communities: Democratic therapeutic community model - extended residential programmes
• Functional family therapy: For adolescents with conduct disorder (prevention)
• Multi-systemic therapy (MST): For young people at risk of ASPD
• Substance misuse treatment: Integrated approach

Pharmacological

• No medication recommended for core ASPD features
• Treat comorbid conditions on their own merits:
  • Depression: SSRI
  • ADHD: Stimulant medication (with careful monitoring)
  • Psychosis: Antipsychotic
• Avoid prescribing drugs with abuse potential (benzodiazepines, opioids)

Referral Criteria

• Forensic risk - forensic psychiatry/psychology
• Comorbid substance misuse - specialist addiction services
• Young people with conduct disorder - CAMHS
• DSPD (dangerous and severe personality disorder) units - specialist services

• Antisocial behaviour tends to attenuate after age 40 - particularly impulsivity and aggression
• Psychopathic traits (callousness, manipulativeness) tend to persist
• Mortality: Increased (substance misuse, violence, suicide, accidents) - life expectancy reduced by ~18 years
• Treatment response: Generally poor; best outcomes with early intervention in conduct disorder
• DSPD programme: Intensive treatment for highest-risk individuals - limited evidence of effectiveness
• Comorbid substance misuse significantly worsens prognosis and increases violence risk

Hare's Psychopathy Checklist (PCL-R) Factors

Conduct Disorder Predictors of ASPD

Key Facts

Eating disorders are characterised by disturbed eating behaviours, body image distortion, and associated physical and psychological consequences. They are among the most lethal psychiatric conditions.

Epidemiology

Eating disorders affect approximately 1.25 million people in the UK. Anorexia nervosa prevalence ~0.3-0.5%; bulimia nervosa ~1-2%; binge eating disorder ~2-3%. Peak onset in adolescence and young adulthood. F:M ratio approximately 10:1 for anorexia, 3:1 for binge eating disorder. Increasing recognition in males and older adults.

Aetiology

• Biological: Genetic heritability ~50-80% for anorexia; serotonergic and dopaminergic dysfunction; reward pathway alterations
• Psychological: Perfectionism, low self-esteem, body dissatisfaction, need for control, trauma
• Sociocultural: Thin-ideal internalisation, diet culture, social media, occupational pressure (dance, athletics, modelling)
• Family factors: Enmeshment, overprotection, family conflict (though causal role debated)

Pathophysiology

Starvation effects (anorexia nervosa):

• Hypothalamic-pituitary-gonadal axis suppression → amenorrhoea
• Reduced metabolic rate, hypothermia, bradycardia
• Bone loss (osteoporosis) - oestrogen deficiency + cortisol excess + nutritional deficiency
• Cardiac muscle wasting → arrhythmias, QTc prolongation
• Refeeding syndrome risk - phosphate, potassium, magnesium depletion

Purging effects (bulimia):

• Hypokalaemic metabolic alkalosis (vomiting) or metabolic acidosis (laxative abuse)
• Dental erosion (perimolysis), parotid gland enlargement
• Mallory-Weiss tears, oesophageal rupture (rare)

Anorexia Nervosa

• Significantly low body weight (BMI <17.5) through restriction ± purging
• Intense fear of gaining weight despite being underweight
• Body image distortion - overestimation of body size
• Amenorrhoea (no longer required for diagnosis but often present)
• Subtypes: Restricting type vs binge-purge type

Bulimia Nervosa

• Recurrent binge eating (≥1/week for ≥3 months) with compensatory behaviours
• Compensatory: Self-induced vomiting, laxative abuse, excessive exercise, fasting
• Normal or slightly above-normal weight
• Self-evaluation unduly influenced by body shape/weight

Binge Eating Disorder

• Recurrent binge eating without regular compensatory behaviours
• Eating rapidly, until uncomfortable, when not hungry, alone, feeling disgusted/guilty
• Marked distress about binge eating
• Often overweight or obese

Red Flags - Medical Emergency

• BMI <13 or rapid weight loss >1kg/week
• Heart rate <40 bpm, QTc prolongation
• Potassium <2.5 mmol/L or other severe electrolyte disturbance
• Syncope, chest pain, muscle weakness
• Hypothermia (<35°C), dehydration
• Suicide risk (elevated in all eating disorders)

Bedside

• BMI: Weight and height - BMI <17.5 (AN), <15 (severe), <13 (critical)
• Vital signs: HR, BP (lying and standing - postural drop), temperature
• ECG: QTc prolongation, bradycardia, U waves (hypokalaemia)
• SIT-UP-SQUAT-STAND (SUSS) test: Proximal muscle strength

Bloods

• U&Es: Hypokalaemia (vomiting/laxatives), hyponatraemia, raised urea
• FBC: Pancytopenia (bone marrow suppression in severe AN)
• LFTs: Raised in starvation or refeeding
• Phosphate, magnesium, calcium: Refeeding risk assessment
• Glucose: Hypoglycaemia in severe AN
• TFTs: Low T3 (sick euthyroid), exclude hyperthyroidism
• Bone profile + vitamin D: Osteoporosis risk
• Amylase: Elevated in vomiting (salivary amylase)
• LH, FSH, oestradiol: Hypothalamic-pituitary-gonadal suppression

Imaging

• DEXA scan: Osteoporosis assessment if amenorrhoea >12 months or BMI <15
• Echocardiogram: If cardiac symptoms or very low BMI

Special Tests

• EDE-Q: Eating Disorder Examination Questionnaire - measures severity
• SCOFF questionnaire: Screening (5 questions: Sick, Control, One stone, Fat, Food)

Non-pharmacological (NICE NG69)

Anorexia nervosa:

• Children/adolescents: Family-based treatment (FBT/Maudsley model) - first-line; parents take control of feeding
• Adults: Individual eating-disorder-focused CBT (CBT-ED), MANTRA (Maudsley Anorexia Nervosa Treatment for Adults), or SSCM (Specialist Supportive Clinical Management)
• Nutritional rehabilitation: Dietitian-led, gradual increase (avoid refeeding syndrome)
• MARSIPAN guidelines: Medical management of severely ill patients

Bulimia nervosa:

• CBT-BN (CBT for bulimia nervosa): 16-20 sessions - first-line
• Guided self-help: Based on CBT principles - step 1

Binge eating disorder:

• Guided self-help based on CBT - first-line
• Group CBT if guided self-help ineffective

Pharmacological

• Fluoxetine 60mg OD: Evidence for bulimia nervosa (reduces binge-purge frequency) - NOT first-line for anorexia nervosa
• Olanzapine: Small evidence base for weight gain in severe AN (off-label)
• SSRIs: For comorbid depression/anxiety (after weight restoration in AN - SSRIs less effective at low weight)
• Refeeding protocol: Start 10 kcal/kg/day (5 if very high risk); supplement phosphate, K⁺, Mg²⁺, thiamine (Pabrinex)

Referral Criteria

• Suspected eating disorder - specialist eating disorder service
• BMI <15 or rapid weight loss - urgent medical assessment
• Medical complications - may need inpatient medical care
• Under 18 - CAMHS eating disorder service
• Treatment under Mental Health Act - if refusing life-saving treatment and meets criteria

• Anorexia nervosa: Standardised mortality ratio 5-6× expected; ~20% develop chronic course; ~50% fully recover
• Bulimia nervosa: Better prognosis; ~50% recovery with CBT; ~30% partial recovery
• Binge eating disorder: Good response to psychological treatment; often comorbid with obesity
• Cause of death in AN: Cardiac arrhythmia (~30%), suicide (~20%), medical complications (~50%)
• Poor prognostic factors: Late onset, binge-purge subtype, comorbid depression, low BMI, longer duration before treatment
• Duration of illness before treatment is the strongest predictor of outcome - early intervention is key

SCOFF Screening Questionnaire

Medical Complications by System

Key Facts

Anorexia nervosa is a severe eating disorder with the highest mortality of any psychiatric condition. Early intervention significantly improves outcomes.

Epidemiology

Prevalence approximately 0.3-0.5%; F:M ~10:1. Peak onset 14-18 years. Incidence increasing. Highest mortality of any psychiatric disorder (SMR 5-6×).

Aetiology

• Genetic: Heritability ~50-80% (highest of eating disorders); genome-wide studies implicate metabolic and psychiatric loci
• Personality: Perfectionism, harm avoidance, obsessionality, low self-esteem
• Neurobiological: Altered serotonergic function, reward pathway dysfunction, set-point theory
• Environmental: Diet culture, social media, bullying, athletic/dance careers

Pathophysiology

Starvation syndrome (Keys Minnesota Experiment):

• Metabolic adaptation: Reduced BMR, hypothermia, bradycardia
• Hormonal: Low leptin, low T3, high cortisol, suppressed HPG axis
• Cardiac: Myocardial atrophy, QTc prolongation, pericardial effusion
• Haematological: Pancytopenia (gelatinous bone marrow transformation)
• Skeletal: Osteoporosis (oestrogen deficiency + hypercortisolaemia + poor nutrition)
• Cerebral: Grey matter loss (partially reversible with weight restoration)

Physical Signs

• Emaciation, cachexia, muscle wasting
• Lanugo hair, dry skin, hair loss, orange discolouration of palms (hypercarotenaemia)
• Hypothermia, bradycardia (<40 bpm), hypotension, postural drop
• Peripheral oedema, parotid swelling (binge-purge subtype)
• Russell's sign (calluses on knuckles from self-induced vomiting)
• Amenorrhoea

Psychological Features

• Body image distortion - overestimation of body size
• Intense fear of weight gain despite being underweight
• Denial of severity, poor insight (egosyntonic)
• Food-related rituals, calorie counting, body checking
• Social withdrawal, mood disturbance, irritability

Red Flags - MARSIPAN Criteria for Medical Emergency

• BMI <13 or rapid weight loss >1kg/week
• HR <40 bpm, QTc >450ms
• K⁺ <2.5, Na⁺ <130, glucose <3.0
• Temperature <35°C
• Unable to stand from squatting (SUSS test score 0)
• Syncope, seizures, cardiac failure

Bedside

• BMI: Height and weight - calculate and plot trend
• Vital signs: HR, BP (lying/standing), temperature
• ECG: Bradycardia, QTc prolongation, ST changes
• SUSS test: Sit up, squat, stand - assess proximal myopathy

Bloods

• U&Es: K⁺, Na⁺, urea, creatinine - electrolyte disturbance
• FBC: Pancytopenia (bone marrow suppression)
• LFTs: Raised transaminases (starvation hepatitis or refeeding)
• Phosphate, Mg²⁺: Refeeding risk; phosphate <0.5 = critical
• Glucose: Hypoglycaemia
• TFTs: Low T3 (sick euthyroid)
• Bone profile, vitamin D: Osteoporosis risk
• LH, FSH, oestradiol: Suppressed (functional hypothalamic amenorrhoea)
• Cortisol: Elevated (HPA axis activation)

Imaging

• DEXA scan: If amenorrhoea >12 months or BMI <15 for >1 year
• Echocardiogram: If cardiac symptoms or BMI <14

Special Tests

• EDE-Q: Eating disorder severity measure
• CIA (Clinical Impairment Assessment): Functional impact

Non-pharmacological (NICE NG69)

Children and adolescents:

• FBT (Family-based treatment): First-line; 3 phases over 12 months: Phase 1 (parents take control of eating), Phase 2 (gradual return of control to adolescent), Phase 3 (establishing healthy independence)
• Adolescent-focused therapy as alternative

Adults:

• CBT-ED: Individual CBT adapted for eating disorders (40 sessions)
• MANTRA: Maudsley Model of AN Treatment for Adults - addresses maintaining factors
• SSCM: Specialist Supportive Clinical Management - nutritional counselling + supportive therapy

Medical stabilisation:

• Refeeding protocol: Start 10 kcal/kg/day (5 if critical); increase by 200-300 kcal every 2-3 days
• Supplement: Pabrinex IV (B vitamins), phosphate (Phosphate-Sandoz 2 tablets TDS), K⁺, Mg²⁺
• Cardiac monitoring: Continuous if HR <40 or QTc >450ms
• Target weight gain: 0.5-1kg/week (inpatient), 0.5kg/week (outpatient)

Pharmacological

• No medication has robust evidence for weight gain in AN
• Olanzapine 2.5-5mg: Small studies suggest modest weight gain; may reduce rumination (off-label)
• SSRIs: For comorbid depression/anxiety AFTER weight restoration (ineffective at low weight)
• Calcium + vitamin D: Bone protection
• Not recommended: Appetite stimulants, zinc, multi-vitamins (beyond standard supplementation)

Referral Criteria

• Suspected AN - specialist eating disorder service
• BMI <15 or medically unstable - urgent medical assessment
• Under 18 - CAMHS eating disorder service
• Refusing treatment with life-threatening illness - consider MHA (rare, case-by-case)

• Recovery: ~50% fully recover; ~30% partial recovery; ~20% chronic course
• Mortality: ~5-20% lifetime; ~5-6× expected (SMR); leading causes: cardiac arrest, suicide
• Suicide: Second leading cause of death in AN; lifetime rate ~5-7%
• Duration of illness before treatment is the strongest prognostic factor
• Good prognostic factors: Younger onset, shorter duration, restricting subtype, good premorbid functioning
• Poor prognostic factors: Late onset, binge-purge subtype, lower BMI at presentation, comorbid depression/OCD, longer duration
• Osteoporosis: May not fully reverse even with weight restoration

MARSIPAN Risk Assessment Framework

Weight Restoration Goals

Key Facts

Bulimia nervosa involves cycles of binge eating and compensatory purging behaviours. Unlike anorexia, weight is often normal, which may delay recognition.

Epidemiology

Prevalence ~1-2%; F:M ~10:1. Peak onset 18-25 years. Higher prevalence in Western countries. Often hidden due to shame - average delay to treatment ~5 years.

Aetiology

• Genetic: Heritability ~55-60%; shared genetic risk with AN and other psychiatric disorders

• Neurobiological: Serotonergic dysfunction, altered reward pathways, impaired satiety signals
• Environmental: Dieting, media pressure, peer influences, childhood adversity

Pathophysiology

• Vomiting: Hypokalaemic metabolic alkalosis; dental erosion; Mallory-Weiss tears; parotid hypertrophy
• Laxative abuse: Metabolic acidosis, dehydration, chronic constipation (lazy bowel)
• Ipecac abuse: Cardiomyopathy (rare but potentially fatal)

Core Features

• Recurrent binge eating: Large amounts in short time, sense of loss of control
• Compensatory behaviours: Self-induced vomiting, laxative/diuretic abuse, excessive exercise, fasting
• Self-evaluation excessively influenced by body shape and weight
• Normal or near-normal weight

Physical Signs

• Russell's sign (calluses on knuckles)
• Parotid gland enlargement ('chipmunk cheeks')
• Dental erosion (perimolysis - especially lingual surfaces of upper teeth)
• Periorbital petechiae (forceful vomiting)
• Oedema (fluid shifts)

Red Flags

• Severe hypokalaemia (<2.5 mmol/L) - cardiac arrhythmia risk
• Haematemesis - Mallory-Weiss tear or Boerhaave syndrome
• Syncope, palpitations - cardiac complications
• Suicidal ideation - elevated risk

Bedside

• BMI: Usually normal (18.5-30)
• Vital signs: HR, BP (postural drop if dehydrated)
• ECG: QTc prolongation, U waves (hypokalaemia)
• Dental examination: Erosion pattern

Bloods

• U&Es: Hypokalaemia, hyponatraemia, raised urea (dehydration)
• Bicarbonate: Elevated (metabolic alkalosis from vomiting) or low (laxative abuse)
• Amylase: Raised (salivary, from vomiting)
• FBC, LFTs, TFTs: Baseline
• Phosphate, Mg²⁺: Electrolyte status

Special Tests

• EDE-Q: Eating disorder severity assessment
• SCOFF questionnaire: Screening

Non-pharmacological (NICE NG69)

• Step 1: Guided self-help based on CBT (4-9 sessions over 16 weeks)
• Step 2: CBT-BN (16-20 sessions) - first-line definitive treatment; ~50% achieve abstinence from binge-purge behaviours
• Alternative: Interpersonal therapy (IPT) if CBT not effective
• Dietary guidance: Regular eating pattern (3 meals + 2-3 snacks), avoid dietary restriction

Pharmacological

• Fluoxetine 60mg OD: Recommended alongside or after CBT; reduces binge-purge frequency by ~50%
• Higher dose than for depression (60mg vs 20mg)
• Other SSRIs have less evidence
• Not recommended: TCAs (cardiac risk), MAOIs

Referral Criteria

• Suspected bulimia - specialist eating disorder service
• Medical complications - medical assessment
• Failed guided self-help - step up to specialist CBT-BN
• Severe electrolyte disturbance - urgent medical admission

• CBT-BN: ~50% achieve remission; ~30% partial improvement; ~20% chronic course
• Better prognosis than anorexia nervosa; lower mortality (SMR ~2×)
• Recovery: ~50-70% recover with treatment; relapse common (30-50%)
• Suicide: Elevated risk but lower than AN
• Good prognostic factors: Shorter duration, earlier treatment, absence of comorbid personality disorder
• Long-term dental damage may be permanent
• Medical complications generally reversible with cessation of purging

Electrolyte Patterns in Purging

Key Facts

BED is the most common eating disorder. It involves recurrent binge eating without compensatory behaviours. It is strongly associated with obesity and metabolic complications.

Epidemiology

Prevalence 2-3% in the general population. More equal sex distribution (F:M ~3:2). Peak onset late teens to early 20s but can present at any age. Found across all weight ranges but most commonly in overweight/obese individuals.

Aetiology

• Genetic: Heritability ~40-50%
• Psychological: Emotional eating as coping mechanism, low self-esteem, body dissatisfaction
• Dietary: History of dieting, food restriction → rebound binge eating
• Neurobiological: Reward pathway dysfunction, impaired impulse control, altered satiety signalling

Pathophysiology

• Reward pathway dysfunction: Enhanced response to food cues, reduced post-meal satiety signalling
• Insulin resistance and metabolic syndrome develop secondary to obesity and binge eating patterns

Diagnostic Features

• Recurrent binge eating episodes with ≥3 of: Eating rapidly, eating until uncomfortably full, eating when not physically hungry, eating alone due to embarrassment, feeling disgusted/depressed/guilty afterwards
• Marked distress about binge eating
• ≥1 episode/week for ≥3 months
• No compensatory behaviours (distinguishes from bulimia)

Associated Features

• Often overweight or obese
• Eating in secret, hoarding food
• Chaotic eating patterns
• Depression, anxiety, social withdrawal
• Type 2 diabetes, hypertension, dyslipidaemia (metabolic syndrome)

Red Flags

• Suicidal ideation (comorbid depression)
• Severe obesity with medical complications (BMI >40)
• Comorbid substance misuse
• Development of compensatory behaviours (reclassify as bulimia)

Bedside

• BMI: Often >25; assess weight trajectory
• BP, waist circumference: Metabolic syndrome assessment
• BED-7/EDE-Q: Severity assessment

Bloods

• HbA1c, fasting glucose: Diabetes screening
• Lipid profile: Dyslipidaemia
• LFTs: Fatty liver disease (NAFLD)
• TFTs: Exclude hypothyroidism
• FBC, U&Es: Baseline

Special Tests

• Formal assessment of binge eating: EDE interview
• PHQ-9, GAD-7: Comorbid depression and anxiety

Non-pharmacological (NICE NG69)

• First-line: Guided self-help based on CBT principles (4-9 sessions)
• Second-line: Group CBT-BED (adapted for binge eating)
• Note: Weight loss is NOT the primary goal - reducing binge eating is the focus
• Exercise for wellbeing (not compensatory)

Pharmacological

• No medication is first-line for BED
• SSRI (fluoxetine 60mg OD): May reduce binge frequency (off-label)
• Lisdexamfetamine (Elvanse): Licensed in US for BED; specialist use only in UK (off-label); reduces binge days by ~50%
• Topiramate: Evidence for binge reduction and weight loss, but significant side effects (cognitive, teratogenic)
• Orlistat/GLP-1 agonists: For weight management if obesity is a concern, alongside eating disorder treatment

Referral Criteria

• Suspected BED - specialist eating disorder service
• Failed guided self-help - step up to group CBT
• Severe obesity with medical complications - combined ED and obesity service
• Comorbid depression/substance misuse - MDT approach

• Best prognosis of the eating disorders
• CBT: ~50-60% achieve remission from binge eating
• Often chronic-relapsing without treatment
• Weight loss is often limited even when binge eating resolves - separate weight management may be needed
• Medical complications: Related to obesity - T2DM, CVD, NAFLD, OSA
• Comorbid depression worsens outcomes

BED vs Bulimia Nervosa

Key Facts

ADHD is one of the most common neurodevelopmental disorders. It persists into adulthood in approximately 65% of cases. Early diagnosis and management significantly improve functional outcomes.

Epidemiology

Prevalence ~3-5% in children, ~2-3% in adults. M:F 3:1 in children (diagnosis increasingly recognised in women). Often coexists with ASD, learning disabilities, anxiety, depression, and conduct disorder.

Aetiology

• Genetic: Heritability ~75-80% (one of the most heritable psychiatric conditions); polygenic - multiple genes of small effect (DAT1, DRD4, DRD5)
• Neurobiological: Prefrontal cortex hypofunction, dopaminergic and noradrenergic deficiency
• Environmental: Prematurity, low birth weight, prenatal tobacco/alcohol exposure, lead exposure
• NOT caused by: Poor parenting, sugar, food additives (though diet may modestly affect symptoms)

Pathophysiology

• Prefrontal cortex dysfunction: Executive function deficits - working memory, planning, impulse control, sustained attention
• Dopamine/noradrenaline deficiency: In prefrontal-striatal circuits; basis for stimulant medication
• Reward pathway alteration: Preference for immediate over delayed rewards (delay aversion)
• Default mode network (DMN): Failure to suppress DMN during tasks → mind-wandering

Inattentive Symptoms (≥6 of 9 in children; ≥5 in adults ≥17)

• Fails to attend to details, careless mistakes
• Difficulty sustaining attention
• Does not seem to listen when spoken to
• Fails to follow through on instructions/finish tasks
• Difficulty organising tasks
• Avoids tasks requiring sustained mental effort
• Loses things necessary for tasks
• Easily distracted
• Forgetful in daily activities

Hyperactive-Impulsive Symptoms (≥6/5)

• Fidgets, squirms
• Leaves seat when remaining seated expected
• Runs/climbs inappropriately (restlessness in adults)
• Unable to engage in activities quietly
• 'On the go' or 'driven by a motor'
• Talks excessively
• Blurts out answers
• Difficulty waiting turn
• Interrupts or intrudes on others

Red Flags

• Academic failure or work underperformance - screen for ADHD
• Substance misuse (self-medication) - common comorbidity
• Traffic accidents - impulsivity and inattention increase risk
• Emotional dysregulation - frequently misdiagnosed as personality disorder or bipolar disorder

Bedside

• DIVA 5.0 (Diagnostic Interview for ADHD in Adults): Structured diagnostic interview
• Conners' Rating Scales: Parent, teacher, and self-report versions
• QB Test: Computerised continuous performance test with motion tracking (NICE-endorsed)
• Developmental history: Symptoms before age 12, multiple settings

Bloods

• TFTs: Exclude hyperthyroidism
• FBC, U&Es, LFTs: Baseline before medication

Special Tests

• Cardiovascular assessment: HR, BP - baseline and after each dose change
• ECG: If family history of cardiac disease or structural heart defects
• Height and weight: Monitor in children on stimulants (growth suppression)

Non-pharmacological

• Psychoeducation: Understanding ADHD, environmental strategies
• Behavioural strategies: Structured routines, organisational aids, timers, checklists
• Parent training programmes: First-line for pre-school children (NICE NG87)
• CBT: For adults with ADHD - addresses executive function and emotional dysregulation
• Workplace/educational adjustments: Extra time in exams, reduced distractions

Pharmacological (NICE NG87)

Children ≥5 and young people:

• First-line: Methylphenidate (Medikinet XL 10-60mg OD or Concerta XL 18-54mg OD)
• Second-line: Lisdexamfetamine (Elvanse) 20-70mg OD
• Third-line: Dexamfetamine, atomoxetine (non-stimulant), guanfacine (non-stimulant)

Adults:

• First-line: Lisdexamfetamine (Elvanse) 30-70mg OD or methylphenidate
• Second-line: Dexamfetamine, atomoxetine

Monitoring:

• HR, BP at baseline, after each dose change, then 6-monthly
• Height and weight every 6 months in children
• Annual cardiovascular and growth review

Referral Criteria

• Suspected ADHD - specialist ADHD/neurodevelopmental service (diagnosis must be by specialist)
• Children: Paediatrician or CAMHS
• Adults: Adult ADHD service
• Comorbid conditions - MDT approach

• Persistence: ~65% of children with ADHD continue to meet criteria in adulthood
• Medication: Stimulants effective in ~70-80% (NNT ~3); improve attention, reduce hyperactivity-impulsivity
• Without treatment: Increased risk of academic failure, unemployment, substance misuse, accidents, criminal behaviour
• With treatment: Functional outcomes significantly improved; reduced accident and substance misuse risk
• Growth: Stimulants may reduce height by ~1-2cm in childhood (effect diminishes and may catch up)
• Substance misuse: Paradoxically, treating ADHD with stimulants reduces later substance misuse risk

ADHD Medication Comparison

Key Facts

ASD is a lifelong neurodevelopmental condition with wide variation in presentation and functioning. The shift from categorical (Asperger's, autism) to a spectrum model reflects the heterogeneity of the condition.

Epidemiology

Prevalence ~1-2% of the population (~700,000 in the UK). M:F ~3:1 (increasing recognition that many women are undiagnosed due to 'masking'). Diagnosis increasingly made in adulthood. Strong genetic component.

Aetiology

• Genetic: Heritability ~80-90%; hundreds of genes implicated; monozygotic twin concordance ~60-90%
• Neurobiological: Altered connectivity (particularly long-range connections), differences in mirror neurone system, amygdala, and fusiform face area
• Environmental: Advanced paternal age, prenatal infections, valproate exposure (MHRA warning)
• NOT caused by: MMR vaccine (thoroughly debunked - Wakefield study retracted)

Pathophysiology

• Altered neural connectivity: Local over-connectivity with reduced long-range connectivity
• Theory of mind deficits: Difficulty understanding others' mental states (but not absent in all)
• Weak central coherence: Tendency to focus on details rather than global picture
• Executive function difficulties: Planning, flexibility, working memory
• Sensory processing differences: Hyper- or hypo-sensitivity to sensory stimuli

Social Communication and Interaction

• Difficulty with reciprocal conversation and non-verbal communication (eye contact, gestures, facial expressions)
• Challenges in developing, maintaining, and understanding relationships
• Difficulty with social-emotional reciprocity (sharing emotions, turn-taking)
• Literal interpretation of language, difficulty with sarcasm, idioms, humour

Restricted, Repetitive Behaviours and Interests

• Stereotyped motor movements (hand flapping, rocking)
• Insistence on sameness, inflexible adherence to routines
• Highly focused, intense interests
• Sensory hyper- or hypo-reactivity (e.g., distress at certain sounds, fascination with lights)

Presentation Across the Lifespan

• Children: May present with language delay, play differences, social difficulties, behavioural challenges
• Adults: May present seeking diagnosis after recognising traits, often after child's diagnosis; social difficulties, anxiety, employment challenges
• Women: Often 'camouflage' - consciously mask difficulties; diagnosis frequently delayed

Red Flags for Assessment Referral

• Regression of language or social skills (especially age 18-24 months)
• Absence of pointing/joint attention by 14 months
• No single words by 16 months or 2-word phrases by 24 months
• Social difficulties across settings (not explained by anxiety alone)

Bedside

• ADOS-2: Gold standard observation-based assessment of social communication and behaviour
• ADI-R: Semi-structured parent interview covering developmental history
• Developmental history: Milestones, early social behaviours, school reports
• AQ-10/AQ-50: Screening tools (Autism Quotient)

Bloods

• Not routinely required for diagnosis
• Genetic testing (chromosomal microarray): If dysmorphic features or intellectual disability
• Fragile X testing: If intellectual disability present
• Lead levels, metabolic screen: If developmental regression

Special Tests

• Cognitive assessment (WAIS/WISC): Assess intellectual functioning
• Hearing test: Exclude hearing loss in children with language delay
• Sensory profile assessment: Occupational therapy
• EEG: If epilepsy suspected (~20-30% comorbidity)

Non-pharmacological (NICE CG128/CG142)

• Psychoeducation: Understanding ASD for individual and family
• Environmental modifications: Sensory-friendly environments, visual schedules, structured routines
• Social skills programmes: For children and young people
• Speech and language therapy: Pragmatic communication support
• Occupational therapy: Sensory processing, daily living skills
• Behavioural support: PBS (Positive Behaviour Support) for challenging behaviour - NOT ABA in isolation
• CBT (adapted): For comorbid anxiety and depression
• Education: EHCP (Education, Health and Care Plan) for support in school

Pharmacological

• No medication for core ASD features
• Treat comorbidities:
  • Anxiety: SSRIs (start low, go slow - increased sensitivity)
  • ADHD: Methylphenidate or atomoxetine (may be less well-tolerated)
  • Sleep disturbance: Melatonin 2-5mg ON (commonly used, evidence-based)
  • Aggression/irritability: Risperidone 0.25-2mg (short-term, specialist only - significant metabolic side effects)
• Avoid polypharmacy

Referral Criteria

• Suspected ASD - specialist neurodevelopmental assessment service
• Children: Community paediatrics or CAMHS
• Adults: Adult ASD assessment service
• Complex needs: MDT including SALT, OT, psychology, psychiatry

• Lifelong condition: ASD is not a disease to be 'cured' - focus on support, adaptation, and quality of life
• Variable outcome: Some live independently, work, and have relationships; others require lifelong support
• Good prognostic factors: Average/above-average IQ, early intervention, language development, supportive environment
• Comorbidities significantly affect quality of life: Anxiety, depression, epilepsy, sleep disorders
• Life expectancy: Reduced by ~16-30 years compared to general population (largely driven by those with intellectual disability, epilepsy, and accidents)
• Employment: Only ~22% of autistic adults in the UK are in any kind of employment

DSM-5 Severity Levels

Autism vs ADHD Comparison

Key Facts

Intellectual disability involves significant limitations in both intellectual functioning and adaptive behaviour. It is a lifelong condition requiring tailored support and reasonable adjustments.

Epidemiology

Prevalence ~1-3% of the population (~1.5 million in England). Mild ID is most common (~85%). Life expectancy has increased but remains reduced compared to general population (median ~58 years overall; ~65 for mild ID).

Aetiology

Genetic causes (~50%):

• Chromosomal: Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), Patau syndrome (trisomy 13), Turner syndrome, Klinefelter syndrome
• Single gene: Fragile X syndrome (most common inherited cause), PKU, tuberous sclerosis, Rett syndrome
• Microdeletion: 22q11.2 deletion (DiGeorge), Williams syndrome, Prader-Willi, Angelman syndrome

Acquired causes (~15%):

• Prenatal: TORCH infections, fetal alcohol spectrum disorder, teratogens
• Perinatal: Birth asphyxia, prematurity, neonatal hypoglycaemia
• Postnatal: Meningitis/encephalitis, head injury, non-accidental injury

Pathophysiology

• Varies by cause - chromosomal abnormalities affect multiple developmental pathways

Severity Levels

• Mild (IQ 50-69): Can often live independently with support; literate; may work in supported or open employment
• Moderate (IQ 35-49): Some self-care skills; supervised work possible; limited academic skills
• Severe (IQ 20-34): Requires substantial support; limited communication; basic self-care
• Profound (IQ <20): Requires continuous support; minimal communication; dependent for all care

Associated Features

• Communication difficulties (speech delay, limited language)
• Challenging behaviour (often communicative - pain, distress, unmet needs)
• Physical comorbidities: Epilepsy (20-50%), sensory impairment, dysphagia, constipation
• Mental health comorbidity: ~30-50% (anxiety, depression, psychosis, ADHD, ASD)

Red Flags

• Sudden behaviour change - consider pain, infection, constipation, medication side effects ('diagnostic overshadowing')
• Epilepsy - higher prevalence and more difficult to treat
• Dysphagia - aspiration pneumonia risk
• Safeguarding concerns - vulnerability to abuse/exploitation
• Regression of skills - consider dementia (especially in Down syndrome >40 years)

Bedside

• Cognitive assessment: WAIS-IV (adults), WISC-V (children) - IQ and profile
• Adaptive behaviour assessment: Vineland Adaptive Behaviour Scales, ABAS-3
• Physical examination: Dysmorphic features, neurological examination

Bloods

• TFTs: Especially in Down syndrome (hypothyroidism common)
• FBC: Baseline
• Genetic testing: Chromosomal microarray, karyotype; specific tests (Fragile X, PKU)

Imaging

• MRI brain: Structural abnormalities if cause unclear
• Echocardiogram: Down syndrome (congenital heart disease in ~50%)

Special Tests

• Hearing and vision assessment: High prevalence of sensory impairment
• EEG: If epilepsy suspected
• Newborn screening: PKU, CHT (identified on bloodspot)

Non-pharmacological

• Person-centred approach: Communication support (Makaton, PECS, easy-read materials)
• Positive behaviour support (PBS): First-line for challenging behaviour (NICE NG54); understand function of behaviour, proactive strategies
• Education: EHCP; special educational needs provision
• Supported living: Appropriate accommodation and support
• Annual health check: GP learning disability DES - physical health, medication review, screening
• Reasonable adjustments: Accessible healthcare, easy-read information, longer appointments

Pharmacological

• STOMP principles: Do not use psychotropic medication as first-line for challenging behaviour
• Only prescribe psychotropics for diagnosed mental health conditions or if behaviour poses significant risk AND non-pharmacological approaches have been tried
• If needed: Risperidone 0.25-2mg for aggression (short-term, specialist), SSRIs for depression/anxiety
• Regular medication review: STOMP-STAMP - at least annually
• Treat physical comorbidities: Epilepsy (lamotrigine, levetiracetam - avoid valproate in women), hypothyroidism, constipation

Referral Criteria

• Suspected ID - specialist assessment (paediatrics/psychology)
• Challenging behaviour - community learning disability team
• Mental health problems - specialist LD psychiatry
• Epilepsy - neurology (complex epilepsy in LD is common)
• Safeguarding concerns - safeguarding team

• Life expectancy: Reduced - overall ~58 years; mild ID ~65 years; severe/profound ~40-50 years
• Down syndrome: Life expectancy ~60 years (improved significantly); ~50% develop early-onset Alzheimer's disease by age 60
• Quality of life: Significantly improved with appropriate support, person-centred care, and community integration
• Mortality: Leading causes - respiratory disease, cardiac disease, epilepsy, cancer (often diagnosed late)
• LeDeR programme: Learning from Deaths reviews - identifies inequalities and avoidable deaths in people with LD

Common Genetic Causes

STOMP Principles

Key Facts

BPSD are a major cause of distress for patients and carers, and are the primary reason for care home admission. Non-pharmacological approaches are always first-line.

Epidemiology

Up to 90% of people with dementia experience BPSD. Approximately 850,000 people have dementia in the UK, projected to rise to 1.6 million by 2040. BPSD accounts for a significant proportion of the economic cost of dementia care.

Aetiology

BPSD arise from interaction of:

• Neurobiological factors: Neurodegeneration affecting frontal lobes (disinhibition), temporal lobes (psychosis), cholinergic/serotonergic/dopaminergic dysfunction
• Psychological factors: Premorbid personality, coping mechanisms, unmet psychological needs
• Environmental factors: Overstimulation, understimulation, unfamiliar environment, change in routine
• Physical factors: Pain, infection, constipation, delirium, medication side effects

Pathophysiology

• Alzheimer's disease: Cholinergic deficit, amyloid plaques, neurofibrillary tangles → progressive cognitive decline with BPSD
• Lewy body dementia: Visual hallucinations, fluctuating cognition, parkinsonism - extremely sensitive to antipsychotics (can cause severe neuroleptic sensitivity reactions)
• Frontotemporal dementia: Prominent behavioural changes (disinhibition, apathy, stereotyped behaviour) - often before memory loss
• Vascular dementia: Stepwise decline, focal neurology, emotional lability

Common BPSD

• Apathy: Most common; reduced motivation and engagement
• Agitation/aggression: Physical or verbal; often worst in late afternoon ('sundowning')
• Depression: Low mood, tearfulness, withdrawal
• Anxiety: Fear, worry, restlessness
• Psychosis: Visual hallucinations (especially Lewy body), persecutory delusions
• Sleep disturbance: Reversed sleep-wake cycle
• Wandering: Purposeless walking; exit-seeking or aimless
• Disinhibition: Inappropriate sexual behaviour, loss of social boundaries (especially FTD)
• Repetitive behaviours: Vocalisations, questions, actions

Red Flags - Exclude Before Attributing to BPSD

• Delirium: Acute onset, fluctuating consciousness, medical cause
• Pain: Undertreated - use Abbey Pain Scale for non-verbal patients
• Infection: UTI, pneumonia (very common precipitants)
• Constipation: Frequently overlooked cause of agitation
• Medication side effects: Anticholinergics, opioids, steroids
• Environmental change: New care setting, change of carer

Bedside

• 4AT or AMT: Delirium screening (essential before attributing symptoms to BPSD)
• Abbey Pain Scale: Pain assessment in non-verbal patients
• NPI (Neuropsychiatric Inventory): Gold standard BPSD assessment tool
• ABC chart: Antecedent-Behaviour-Consequence - identify triggers
• Physical examination: Infection screen, constipation check, medication review

Bloods

• FBC, CRP, U&Es: Infection, dehydration
• Urine MC&S: UTI (common trigger)
• TFTs, calcium, B12, folate, glucose: Treatable causes of cognitive/behavioural change
• LFTs: Hepatic encephalopathy

Imaging

• CT/MRI brain: Exclude structural cause if not previously investigated

Special Tests

• Cognitive assessment: MMSE, MoCA, ACE-III - establish baseline and trajectory
• Medication review: Rationalise polypharmacy, identify iatrogenic causes

Non-pharmacological (Always first-line - NICE NG97)

• Person-centred care: Life story work, meaningful activities, validation therapy
• Environmental modifications: Reduce noise, adequate lighting, familiar objects, signage
• Structured activities: Music therapy, reminiscence therapy, art therapy, animal-assisted therapy
• Communication strategies: Simple language, calm tone, non-verbal cues
• Carer support: Education, respite, support groups (Alzheimer's Society)
• Pain management: Ensure adequate analgesia - trial of paracetamol 1g QDS if pain suspected
• Sleep hygiene: Light exposure, reduce daytime napping, evening routine

Pharmacological (NICE NG97 - only if severe distress/risk)

• Treat underlying cause first: Infection, pain, constipation, delirium
• Cholinesterase inhibitors: Donepezil 5-10mg OD - may reduce BPSD in Alzheimer's and Lewy body dementia
• Antipsychotics (severe aggression/psychosis causing significant distress or risk):
  • Risperidone 0.25-1mg (only licensed antipsychotic for BPSD) - short-term (up to 6 weeks), then review
  • Risks: 2× stroke risk, 1.5× mortality risk, falls, sedation, parkinsonism
  • Avoid in Lewy body dementia - severe neuroleptic sensitivity (use quetiapine low-dose if essential)
• Memantine 10-20mg: May help agitation in moderate-severe Alzheimer's
• SSRIs: Sertraline/citalopram for depression in dementia
• Trazodone 25-100mg: For agitation and sleep disturbance (off-label, limited evidence)

Referral Criteria

• Persistent BPSD despite non-pharmacological approaches - old age psychiatry
• Diagnostic uncertainty - memory assessment service
• Carer stress/burnout - social services, carer support
• Safeguarding concerns - safeguarding team

• BPSD typically fluctuate and change over the course of dementia
• Apathy tends to worsen as dementia progresses
• Psychosis is more common in moderate-severe stages
• Agitation is the most common reason for care home admission
• Antipsychotic use: ~2 additional deaths per 100 patients treated for 12 weeks; use should be minimised
• Non-pharmacological interventions: Evidence supports music therapy, structured activities, and person-centred care in reducing BPSD

BPSD Management Algorithm

Antipsychotic Risks in Dementia

Key Facts

Delirium is an acute confusional state caused by an underlying medical condition. It is a medical emergency requiring urgent investigation and treatment of the cause. It is frequently underdiagnosed, especially the hypoactive subtype.

Epidemiology

Affects 20-30% of medical inpatients aged >65; up to 50% of surgical patients; 80% of ICU patients. More common in those with pre-existing dementia (delirium superimposed on dementia). Hypoactive delirium accounts for ~50% of cases but is frequently missed.

Aetiology

Predisposing factors (vulnerability):

• Advanced age, pre-existing dementia, frailty, sensory impairment, polypharmacy, dehydration, immobility

Precipitating factors (triggers):

• Infection (UTI, pneumonia - most common), pain, constipation, urinary retention
• Drugs: Opioids, anticholinergics, benzodiazepines, steroids, alcohol withdrawal
• Metabolic: Electrolyte disturbance, hypoglycaemia, hypoxia, hepatic/renal failure
• Intracranial: Stroke, SDH, meningitis, seizures
• Cardiac: MI, heart failure, arrhythmia
• Surgery: Post-operative delirium (especially hip fracture, cardiac surgery)

Pathophysiology

• Cholinergic deficit: Anticholinergic drugs worsen delirium; basis for avoiding anticholinergics in elderly
• Dopamine excess: Relative to acetylcholine - basis for antipsychotic use when medication needed
• Cortisol elevation: Stress-induced HPA axis activation
• Disrupted circadian rhythms: Melatonin dysregulation → sleep-wake disturbance

Core Features

• Acute onset (hours to days) - key distinguishing feature
• Fluctuating course - symptoms wax and wane, often worse at night ('sundowning')
• Inattention - cardinal feature; cannot maintain focus, easily distractible
• Altered level of consciousness - ranges from hyperalert to drowsy/stuporous
• Cognitive disturbance - disorientation (time > place > person), memory impairment, disorganised thinking
• Perceptual disturbance - visual hallucinations, illusions, misidentifications

Subtypes

• Hyperactive (~25%): Agitation, restlessness, aggression, hallucinations - easily recognised
• Hypoactive (~50%): Withdrawal, drowsiness, reduced activity - frequently missed, often misdiagnosed as depression
• Mixed (~25%): Features of both

Red Flags

• Acute confusion in elderly - always assume delirium until proven otherwise
• Fever + confusion - sepsis screen urgently
• Head injury + confusion - CT head
• Alcohol history + tremor/agitation - alcohol withdrawal (Wernicke's, DTs)
• New focal neurology - stroke/intracranial pathology

Bedside

• 4AT: Rapid screening (Alertness, AMT4, Attention, Acute change); score ≥4 = likely delirium
• SQiD: Single Question in Delirium ('Is this patient more confused than before?')
• Observations: Temperature, HR, BP, RR, SpO2, glucose - NEWS2 score
• Urinalysis: UTI screening
• Medication review: Identify precipitating drugs

Bloods

• FBC, CRP: Infection markers
• U&Es: Electrolyte disturbance, renal failure
• LFTs: Hepatic encephalopathy
• Calcium, glucose: Metabolic causes
• TFTs, B12: If not recently checked
• Blood cultures: If sepsis suspected
• Blood gas: Hypoxia, hypercapnia

Imaging

• CXR: Pneumonia, heart failure
• CT head: If head injury, focal neurology, or no clear cause identified

Special Tests

• LP: If meningitis/encephalitis suspected (fever, neck stiffness, photophobia)
• EEG: If non-convulsive status epilepticus suspected (generalised slowing in delirium)
• Ammonia: If hepatic encephalopathy suspected

Non-pharmacological (NICE CG103 - always first-line)

• Identify and treat underlying cause - the MOST important intervention
• Reorientation: Clock, calendar, familiar objects, consistent staff
• Communication: Clear, simple, calm, with reassurance
• Optimise environment: Adequate lighting, reduce noise, single room if possible
• Maintain sleep-wake cycle: Daytime natural light, reduce night-time disturbance
• Ensure sensory aids: Glasses, hearing aids
• Mobilise early: Reduce immobility-related complications
• Hydration and nutrition: Ensure adequate oral intake, IV fluids if needed
• Avoid restraint: Physical and chemical restraint should be last resort

Pharmacological (NICE CG103 - only if severe distress/risk to self or others)

• Haloperidol 0.5-1mg PO/IM (lowest effective dose, max 5mg/day) - first-line if medication needed
• Avoid in Lewy body dementia and Parkinson's - use lorazepam 0.5-1mg instead
• Lorazepam 0.5-1mg PO/IM: Preferred in alcohol withdrawal, Lewy body dementia, Parkinson's
• Review and discontinue as soon as delirium resolves
• Stop/reduce precipitating medications (anticholinergics, opioids, benzodiazepines)

Referral Criteria

• Refractory delirium - old age psychiatry/liaison psychiatry
• New cognitive impairment persisting after delirium - memory assessment service (6-12 weeks post-delirium)
• Alcohol withdrawal delirium - addiction services
• Complex medical causes - appropriate specialty

• In-hospital mortality: 10-26% (higher than similar patients without delirium)
• 1-year mortality: Up to 35%
• Cognitive outcomes: ~40% of patients do not return to baseline cognitive function
• Incident dementia: Delirium is an independent risk factor for developing new dementia (OR ~8-12× in next 3 years)
• Hospital stay: Delirium increases length of stay by ~7-10 days
• Prevention: Multicomponent interventions (Hospital Elder Life Program/HELP) reduce delirium incidence by 30-40%
• Hypoactive delirium has worse prognosis than hyperactive

4AT Screening Tool

Delirium vs Dementia

Key Facts

Somatoform/somatic symptom disorders involve physical symptoms accompanied by excessive and disproportionate thoughts, feelings, or behaviours. The symptoms are not intentionally produced.

Epidemiology

Approximately 15-30% of primary care consultations involve medically unexplained symptoms. Somatic symptom disorder affects ~5-7% of primary care patients. More common in women and lower socioeconomic groups.

Aetiology

• Biological: Central sensitisation, altered pain processing, autonomic dysregulation, inflammation
• Psychological: Health anxiety, catastrophic misinterpretation of symptoms, somatisation as emotional expression, childhood adversity
• Social: Illness modelling, secondary gain (not conscious), sick role reinforcement

Pathophysiology

• Central sensitisation amplifies normal bodily sensations
• Selective attention to bodily symptoms increases their perceived intensity
• Cortical processing of interoceptive signals is altered - functional MRI shows differences in insular and prefrontal cortex activation
• HPA axis dysregulation and autonomic dysfunction may produce real physiological symptoms

Common Presentations

• Pain: Chronic widespread pain, headache, back pain, abdominal pain
• GI: IBS, non-cardiac chest pain, globus sensation
• Neurological: Functional neurological disorder (weakness, tremor, seizures, sensory loss)
• Fatigue: Chronic fatigue without medical explanation
• Multiple symptoms: Multiple organ systems involved

Key Clinical Features

• Symptoms are disproportionate to any identified pathology
• Excessive time and energy devoted to health concerns
• High healthcare utilisation (frequent GP visits, A&E attendances)
• Persistent despite medical reassurance
• Significant functional impairment

Red Flags

• Exclude organic disease before diagnosing - thorough but focused investigation
• Psychiatric comorbidity: Depression (~50%), anxiety (~50%), personality disorder
• Suicide risk if severe functional impairment and despair
• Iatrogenic harm from unnecessary investigations and treatments

Bedside

• PHQ-15: Somatic symptom severity scale (15 items)
• PHQ-9, GAD-7: Comorbid depression and anxiety
• Functional assessment: Impact on daily life, work, relationships

Bloods

• Focused investigation based on presenting symptoms - avoid shotgun approach
• FBC, TFTs, inflammatory markers as reasonable baseline
• Stop investigating when adequate exclusion of serious pathology achieved

Special Tests

• Guided by clinical presentation - principle of 'just enough' investigation
• Avoid unnecessary imaging and specialist referrals that reinforce illness behaviour

Non-pharmacological

• Therapeutic relationship: Continuity of care with single GP, regular scheduled appointments (not symptom-driven)
• Validation: Acknowledge symptoms are real and distressing
• Explanation: Sensitisation model, stress-symptom link, biopsychosocial framework
• CBT: Most effective treatment - addresses catastrophic thinking, illness behaviour, avoidance; 12-16 sessions
• Graded exercise/activity: Gradual return to function
• Reduce secondary gain: Minimise reinforcement of sick role

Pharmacological

• SSRIs: Sertraline 50-200mg or duloxetine 60-120mg - effective for somatic symptoms even without depression
• Low-dose TCAs: Amitriptyline 10-50mg ON for pain-predominant symptoms
• Pregabalin: 150-600mg/day for pain (off-label in this context)
• Avoid: Opioids, benzodiazepines, unnecessary polypharmacy

Referral Criteria

• Specialist liaison psychiatry/psychological medicine if severe functional impairment
• Persistent symptoms despite primary care management
• Complex comorbidity

• Chronic course in many cases; ~50% improve with treatment, ~20% have poor long-term outcomes
• CBT improves symptoms in ~50-60% of patients
• Comorbid depression and personality disorder worsen prognosis
• Iatrogenic harm from unnecessary investigations/treatments is a significant risk
• Early intervention and explanation improve outcomes

DSM-5 Classification Changes