Acute Psychosis
Summary
Acute psychosis is a psychiatric emergency characterised by the sudden onset of psychotic symptoms including hallucinations, delusions, and disorganised thinking or behaviour. It represents a loss of contact with reality and may be the first presentation of schizophrenia, a manifestation of bipolar disorder, substance-induced, or secondary to organic causes. First episode psychosis (FEP) is particularly important as early intervention within the critical period (first 5 years) significantly improves long-term outcomes. The duration of untreated psychosis (DUP) is inversely related to prognosis — shorter DUP correlates with better recovery.
Key Facts
- Definition: Syndrome of hallucinations, delusions, and/or disorganised behaviour with loss of reality testing
- Incidence: First episode psychosis: 15-35 per 100,000 per year
- Peak Age: 18-25 years (males); 25-35 years (females)
- Mortality/Morbidity: Suicide risk 5-10% lifetime; significant functional impairment without early treatment
- Key Management: Exclude organic causes → risk assessment → antipsychotics + psychological support
- Critical Finding: Duration of untreated psychosis (DUP) predicts outcome — aim for <3 months
- Key Investigation: Organic screen (bloods, CT head, urine drug screen); Mental State Examination
Clinical Pearls
"Always Exclude Organic": Before diagnosing a primary psychiatric disorder, always consider delirium, encephalitis (especially anti-NMDA receptor), drug intoxication/withdrawal, and metabolic causes. A young patient with first-episode psychosis and seizures = think anti-NMDA encephalitis.
Duration of Untreated Psychosis: Studies consistently show that DUP <3 months is associated with significantly better outcomes. Every day counts — early intervention services exist for this reason.
Cannabis and Psychosis: Cannabis use, especially high-potency strains and early-onset use, is a well-established risk factor for developing psychosis. The relationship appears causal, not just correlational.
Why This Matters Clinically
Acute psychosis is frightening for patients and families, carries significant suicide risk, and can become a chronic disabling condition if not treated early and effectively. First episode psychosis represents a critical intervention window — the first 5 years ("critical period") largely determine long-term trajectory. Early specialist intervention significantly improves outcomes.
Incidence & Prevalence
- Incidence of FEP: 15-35 per 100,000 per year
- Lifetime prevalence of schizophrenia: ~1% (0.5-1.5%)
- Prevalence of any psychotic disorder: 3-3.5%
- Trend: Stable in developed countries; some evidence of increased incidence in urban areas
Demographics
| Factor | Details |
|---|---|
| Age | Peak onset 18-25 years (males), 25-35 years (females); second peak in women >5 years |
| Sex | Male:Female = 1.4:1 for schizophrenia; equal for affective psychoses |
| Ethnicity | Higher incidence in migrants and ethnic minorities (social adversity) |
| Geography | Urban > Rural (urbanicity is a risk factor); higher in areas of social deprivation |
Risk Factors
Non-Modifiable:
- First-degree relative with schizophrenia (RR 10x)
- Genetic variants (polygenic risk score)
- Obstetric complications (hypoxia, low birth weight)
- Childhood adversity/trauma
- Male sex (earlier onset)
Modifiable:
| Risk Factor | Relative Risk | Notes |
|---|---|---|
| Cannabis use (high potency/early onset) | 2-6× | Dose-response relationship |
| Stimulant use (amphetamines, cocaine) | 5-10× | Can trigger or exacerbate |
| Social isolation | 2-3× | Urban environment, migration |
| Alcohol misuse | 1.5-2× | Often comorbid |
Aetiology Distribution
| Cause | Frequency |
|---|---|
| Schizophrenia/Schizoaffective | 40-50% |
| Bipolar disorder (manic psychosis) | 15-20% |
| Drug-induced psychosis | 15-25% |
| Brief psychotic disorder | 5-10% |
| Organic/medical causes | 5-10% |
| Depressive psychosis | 5-10% |
Mechanism
Step 1: Dopamine Hypothesis (The Core Model)
- Mesolimbic pathway hyperactivity: Excess dopamine signalling from ventral tegmental area (VTA) to nucleus accumbens and limbic structures leads to positive symptoms (hallucinations, delusions, disorganised thinking)
- Mesocortical pathway hypoactivity: Reduced dopamine in prefrontal cortex leads to negative symptoms (apathy, anhedonia) and cognitive impairment
Step 2: Glutamate Dysfunction (NMDA Receptor Hypofunction)
- Reduced NMDA receptor function on GABAergic interneurons
- Disinhibition of glutamatergic pyramidal neurons
- Downstream effects on dopamine regulation
- Explains why phencyclidine (PCP) and ketamine induce psychotic symptoms
Step 3: Neurodevelopmental Hypothesis
- Early insults (prenatal infection, obstetric complications) cause subtle brain abnormalities
- Normal adolescent synaptic pruning unmasks vulnerability
- Stress and substance use trigger expression of clinical psychosis
Step 4: Sensitisation Model
- Repeated psychotic episodes sensitise dopamine system
- Relapses occur with progressively lower stress thresholds
- Supports early assertive treatment to prevent relapse
Classification
| Type | Definition | Features |
|---|---|---|
| First Episode Psychosis (FEP) | First lifetime psychotic episode | Critical intervention window; may be prodrome to schizophrenia or bipolar |
| Brief Psychotic Disorder | <1 month duration, full remission | Often stress-related; good prognosis |
| Schizophreniform | 1-6 months duration | May evolve to schizophrenia |
| Schizophrenia | > months symptoms | Chronic; requires long-term treatment |
| Schizoaffective Disorder | Schizophrenia + mood episodes | Mixed features |
| Substance-Induced Psychosis | Temporally related to drug use | May persist; cannabis-induced often chronic |
Anatomical/Physiological Considerations
Psychosis involves disruption of multiple brain networks. Structural imaging shows enlarged ventricles, reduced grey matter volume (especially prefrontal and temporal cortex), and white matter abnormalities. Functional imaging demonstrates hypofrontality (reduced prefrontal activation) and aberrant salience signalling in striatal circuits.
Symptoms
Positive Symptoms (Present in acute psychosis):
Negative Symptoms (May be present):
Atypical Presentations:
Signs
Red Flags
[!CAUTION] Red Flags — Urgent assessment required if:
- Fever + rigidity + altered consciousness → Neuroleptic Malignant Syndrome (medical emergency)
- Seizures + psychosis (especially young patient) → Anti-NMDA receptor encephalitis (urgent neurology)
- Fluctuating consciousness → Delirium (treat underlying cause)
- Command hallucinations to harm self/others → Immediate risk (close observation, consider admission)
- First episode + neurological signs → Organic cause (urgent workup)
- Catatonia (immobility, mutism) → Risk of DVT, aspiration; consider lorazepam/ECT
Structured Approach
General:
- Appearance: Self-care, hygiene, unusual clothing/accessories
- Behaviour: Eye contact, psychomotor activity, agitation, catatonia
- Rapport: Guarded, suspicious, or cooperative
Mental State Examination (MSE):
- Appearance & Behaviour: Described above
- Speech: Rate, volume, form (tangential, circumstantial, neologisms)
- Mood: Subjective and objective assessment
- Thought Form: Loosening of associations, thought blocking, word salad
- Thought Content: Delusions (systematised vs fragmentary), suicidal/homicidal ideation
- Perceptions: Hallucinations (modality, content, command)
- Cognition: Orientation, attention, memory (screen for delirium)
- Insight: Awareness of illness, treatment adherence
Physical Examination:
- Vital signs: Fever (infection? NMS?), tachycardia, hypertension
- Neurological: Focal signs, movement disorders, gait
- General: Injection marks, nutritional status
Special Tests
| Test | Purpose | Positive Finding | Notes |
|---|---|---|---|
| Mini-Mental State Examination (MMSE) | Screen for delirium/cognitive impairment | <24/30 suggests impairment | Cannot differentiate cause |
| Montreal Cognitive Assessment (MoCA) | More sensitive for frontal dysfunction | <26/30 suggests impairment | Better for executive function |
| Confusion Assessment Method (CAM) | Diagnose delirium | Acute onset + fluctuation + inattention + altered consciousness | Gold standard for delirium |
| Bush-Francis Catatonia Rating Scale | Assess catatonia | Score > suggests catatonia | Guides lorazepam challenge |
First-Line (Bedside)
- Vital signs — fever, tachycardia (infection? NMS? Substance use?)
- Blood glucose — hypoglycaemia can cause confusion
- Pulse oximetry — hypoxia from any cause
- Urine drug screen — cannabis, amphetamines, cocaine, opioids
- Alcohol breathalyser — if relevant history
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| Full blood count | Leucocytosis (infection); anaemia | Exclude organic cause |
| Urea & Electrolytes | Hyponatraemia (SIADH, water intoxication) | Metabolic screen |
| Liver function tests | Hepatic encephalopathy | Exclude liver failure |
| Thyroid function tests | Hyper/hypothyroidism | Exclude thyroid dysfunction |
| Calcium, Glucose | Hypercalcaemia, hypoglycaemia | Metabolic causes |
| CRP, ESR | Elevated in infection/inflammation | Inflammatory screen |
| Syphilis serology (VDRL) | Neurosyphilis | If risk factors |
| HIV test | HIV encephalopathy | If risk factors |
| Anti-NMDA receptor antibodies | Positive in autoimmune encephalitis | If atypical presentation |
| Urine toxicology | Drugs of abuse | Substance-induced psychosis |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| CT Head | Exclude mass lesion, haemorrhage, hydrocephalus | First episode psychosis; any neurological signs |
| MRI Brain | More sensitive for encephalitis, demyelination | Atypical features, suspected anti-NMDA |
| EEG | Encephalopathic changes, seizure activity | Suspected encephalitis or seizures |
Diagnostic Criteria
DSM-5 Criteria for Schizophrenia (for chronic diagnosis):
- Two or more of: Delusions, hallucinations, disorganised speech, grossly disorganised/catatonic behaviour, negative symptoms
- At least one must be delusions, hallucinations, or disorganised speech
- Duration: Continuous disturbance for ≥6 months (including ≥1 month of active symptoms)
- Functional impairment
- Not attributable to substances or another medical condition
Management Algorithm
Acute/Emergency Management
Immediate Actions (Emergency Department/Acute Psychiatric Setting):
- Ensure safety — reduce stimulation, staff availability, de-escalation
- Rapid assessment — exclude medical causes (bloods, vitals, cognitive screen)
- Risk assessment — suicide risk, violence risk, vulnerability
- Consider immediate sedation if severe agitation threatening safety
Rapid Tranquillisation (if needed):
- First-line: Lorazepam 1-2mg IM/PO (can repeat after 30-60 min)
- Second-line: Haloperidol 5mg IM + Promethazine 25-50mg IM
- Alternative: Olanzapine 10mg IM (do NOT combine with lorazepam IM)
- Monitor: Respiratory rate, BP, consciousness level
Conservative Management
- De-escalation techniques: Calm environment, one-to-one support
- Reduce stimulation: Quiet room, dim lights
- Reassurance: Explain what is happening, that help is available
- Involve family/carers: For collateral history and support
- Address physical needs: Food, drink, rest
Medical Management
| Drug Class | Drug | Dose | Notes |
|---|---|---|---|
| Second-Generation Antipsychotic | Risperidone | 1-2mg BD, titrate to 4-6mg/day | First-line; EPS risk at higher doses |
| Second-Generation Antipsychotic | Olanzapine | 5-10mg OD, max 20mg/day | More sedating; metabolic effects |
| Second-Generation Antipsychotic | Aripiprazole | 10-15mg OD, max 30mg/day | Less metabolic effects; partial agonist |
| Second-Generation Antipsychotic | Quetiapine | 25mg BD, titrate to 300-600mg/day | Sedating; good for affective symptoms |
| First-Generation Antipsychotic | Haloperidol | 0.5-5mg BD | More EPS; useful for acute sedation |
| Benzodiazepine (adjunct) | Lorazepam | 1-2mg PRN | Short-term for anxiety/agitation |
| Treatment-Resistant | Clozapine | Start 12.5mg, slow titration | Only after 2 adequate antipsychotic trials |
Monitoring on Antipsychotics:
- Baseline: Weight, BMI, waist circumference, BP, glucose, lipids, ECG (QTc)
- Ongoing: Weekly weight (first 6 weeks), then monthly; glucose/lipids at 3 months then annually
- Clozapine: Mandatory weekly FBC for 18 weeks, then 2-weekly, then monthly (neutropenia risk)
Specialist Referral
- All first-episode psychosis: Refer to Early Intervention in Psychosis (EIP) service
- Treatment resistance (2 failed trials): Refer for clozapine initiation
- Uncertain diagnosis: Neuropsychiatry for organic causes
- Catatonia: Consider lorazepam challenge, ECT if refractory
Disposition
- Admit if: High risk to self/others; no support; first episode requiring stabilisation; poor insight
- Home Treatment Team if: Lower risk; supportive environment; engaging with treatment
- Mental Health Act assessment: If refusing treatment and meets criteria (risk, mental disorder, necessity)
- Follow-up: Daily initially if in community; EIP within 2 weeks of referral
Immediate (Minutes-Hours)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Acute behavioural disturbance | 30-50% | Agitation, aggression | De-escalation, rapid tranquillisation |
| Self-harm/suicide attempt | 5-10% | Intentional injury, overdose | Risk assessment, close observation |
| Violence to others | 5-10% | Assault, threatening behaviour | Security, restraint if necessary |
| Neuroleptic Malignant Syndrome | <1% | Fever, rigidity, autonomic instability | Stop antipsychotic, IV fluids, dantrolene |
Early (Days-Weeks)
- Extrapyramidal side effects (EPS): Acute dystonia (IM procyclidine), akathisia, parkinsonism
- Sedation and falls
- Postural hypotension
- Medication non-adherence
- Worsening of psychotic symptoms before response (2-6 weeks for full effect)
Late (Months-Years)
- Suicide: 5-10% lifetime mortality in schizophrenia
- Treatment-resistant schizophrenia: 30% do not respond to standard antipsychotics
- Metabolic syndrome: Weight gain, diabetes, dyslipidaemia (especially olanzapine, clozapine)
- Tardive dyskinesia: Irreversible movement disorder (2-5% per year on antipsychotics)
- Social decline: Unemployment, homelessness, social isolation
- Substance misuse: 50% comorbidity
- Relapse: 50-80% within 5 years if medication discontinued
Natural History
Untreated psychosis leads to progressive social and occupational decline. Positive symptoms may fluctuate but negative symptoms and cognitive impairment often worsen. Each psychotic episode is associated with further neurobiological sensitisation, making subsequent episodes more likely with less provocation.
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Full recovery (FEP) | 20-30% have single episode and full recovery |
| Episodic with good inter-episode function | 30-40% |
| Chronic with residual symptoms | 30-40% |
| Suicide | 5-10% lifetime mortality |
| Employment | Only 10-20% in competitive employment |
| Life expectancy | Reduced by 15-20 years vs general population |
Prognostic Factors
Good Prognosis:
- Short duration of untreated psychosis (<3 months)
- Acute onset with clear precipitant
- Good premorbid functioning
- Affective (mood) symptoms present
- Female sex
- Older age at onset
- Good medication adherence
- Strong social support
- Early intervention service involvement
Poor Prognosis:
- Long DUP (>1 year)
- Insidious onset
- Poor premorbid adjustment
- Prominent negative symptoms
- Male sex
- Young age at onset
- Substance misuse (especially cannabis)
- Family history of schizophrenia
- Treatment non-adherence
Key Guidelines
- NICE NG155: Psychosis and Schizophrenia in Adults (2014, updated 2024) — Recommends early intervention services for all FEP; oral antipsychotic at lowest effective dose; CBT for psychosis; regular physical health monitoring. NICE
- RANZCP Clinical Practice Guidelines for Schizophrenia (2016) — Australian guidance emphasising early intervention, psychosocial therapies, and clozapine for treatment resistance. RANZCP
- SIGN 131: Management of Schizophrenia (2013) — Scottish guidance with focus on recovery-oriented care and long-acting injectable antipsychotics for non-adherence.
Landmark Trials
RAISE-ETP (Recovery After an Initial Schizophrenia Episode, 2015) — Landmark US study demonstrating superiority of comprehensive early intervention (NAVIGATE) over usual care.
- 404 patients with FEP randomised
- Key finding: NAVIGATE group had greater improvement in quality of life and symptoms, more time in work/school
- Clinical Impact: Strong evidence base for Early Intervention services
CATIE Trial (Clinical Antipsychotic Trials of Intervention Effectiveness, 2005) — Compared second-generation antipsychotics with first-generation.
- 1,460 patients with schizophrenia
- Key finding: No clear superiority of second-generation antipsychotics; high discontinuation rates in all groups; olanzapine most effective but most metabolic effects
- Clinical Impact: Drug choice should be individualised based on side-effect profile
CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, 2006) — UK study comparing first vs second-generation antipsychotics.
- Key finding: No significant difference in quality of life or symptoms
- Clinical Impact: First-generation antipsychotics remain valid option; choice based on side effects
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Antipsychotics for acute psychosis | 1a | Meta-analyses; all antipsychotics superior to placebo |
| Early Intervention Services | 1b | RAISE-ETP and multiple RCTs |
| CBT for psychosis (adjunct) | 1a | Cochrane reviews showing modest benefit |
| Clozapine for treatment resistance | 1b | RCTs; only antipsychotic proven superior after treatment failure |
| Long-acting injectable antipsychotics | 1a | Meta-analyses showing reduced relapse vs oral |
| Family intervention | 1a | Reduces relapse rates |
What is Acute Psychosis?
Acute psychosis is when someone temporarily loses touch with reality. They may hear voices that others can't hear, strongly believe things that aren't true (like being watched or followed), or think and speak in ways that are hard to follow. It can be very frightening for the person experiencing it and for their loved ones.
Why does it happen?
Psychosis happens when the brain's chemical messengers (especially dopamine) become unbalanced. This can occur because of:
- Mental health conditions like schizophrenia or bipolar disorder
- Drugs (especially cannabis, amphetamines, or new psychoactive substances)
- Extreme stress or sleep deprivation
- Medical problems affecting the brain (infections, hormones)
- Sometimes the cause isn't clear
How is it treated?
- Safety first: Doctors will make sure you're safe and get the right assessments.
- Rule out medical causes: Blood tests and sometimes brain scans to check for physical causes.
- Medication: Antipsychotic medicines help restore chemical balance in the brain. They usually take 2-6 weeks to work fully.
- Talking therapies: Cognitive behavioural therapy (CBT) for psychosis can help.
- Early Intervention Service: A specialist team will provide ongoing support, often for 2-3 years.
What to expect
- The first episode often gets better with treatment
- Many people have just one episode and recover fully
- Taking medication as prescribed is very important to prevent relapses
- Recovery is possible, and many people go on to live fulfilling lives
- It's important to avoid cannabis and other drugs
- Regular check-ups will monitor your physical health (weight, blood sugar)
When to seek help
- If you're hearing voices or having thoughts that frighten you
- If you feel like you can't trust anyone or people are trying to harm you
- If a family member or friend is acting very strangely, not making sense, or seems to be responding to things you can't see or hear
- Urgent: If someone is threatening to harm themselves or others, call 999 (UK) or take them to A&E
Primary Guidelines
- National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. NICE guideline [NG178]. 2014 (updated 2024). PMID: N/A
- Galletly C, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Aust N Z J Psychiatry. 2016;50(5):410-472. PMID: 27106681
Key Trials
- Kane JM, et al. Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program. Am J Psychiatry. 2016;173(4):362-372. PMID: 26481174
- Lieberman JA, et al. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia (CATIE). N Engl J Med. 2005;353(12):1209-1223. PMID: 16172203
- Jones PB, et al. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia (CUtLASS). Arch Gen Psychiatry. 2006;63(10):1079-1087. PMID: 17015810
Further Resources
- Mind (UK): First Episode Psychosis
- NAMI (US): Early Psychosis Information
- Intervoice: Hearing Voices Network
- UpToDate: First episode psychosis in adults
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This content does not constitute medical advice for individual patients.