Hallucinations

A hallucination is a perception that occurs without an external stimulus, has the full force and clarity of a real perception, is not under voluntary control, and occurs in any sensory modality. It is a symptom, not a diagnosis, and it has many causes, from primary psychosis to delirium, neurodegeneration, epilepsy, intoxication, drugs, sensory loss and normal sleep related experiences.

The first task is safety (command hallucinations, harm to self or others), the second is to exclude delirium and treatable organic and toxic causes, and the third is to treat the underlying disorder with the lowest effective dose of an antipsychotic when one is needed.

Definitions. A true hallucination is perceived as external, real and in objective space, with no insight in most cases. A pseudohallucination is perceived as internal or in subjective space, with insight preserved. An illusion is a misperception of a real stimulus. Hypnagogic hallucinations occur at sleep onset and hypnopompic hallucinations at awakening, and are common in healthy people and in narcolepsy.

Functional hallucinations occur only with a real stimulus of the same modality. Extracampine hallucinations are perceived outside the sensory field. Charles Bonnet syndrome is complex visual hallucinations with preserved insight in people with visual loss.

Classification by modality

• Auditory: voices (commenting, conversing, commanding), music, noises. Most common in schizophrenia and in primary psychosis.
• Visual: shapes, people, animals, small figures (Lilliputian), seen in delirium, dementia with Lewy bodies, Parkinson disease, Charles Bonnet syndrome, drug and alcohol effects and epilepsy.
• Olfactory and gustatory: seen in temporal lobe epilepsy (uncinate fits), migraine, brain tumour, sinus disease, depression and psychosis.
• Tactile (haptic) and formication: insects crawling, in alcohol withdrawal, cocaine, amphetamines, delusional infestation and neuropathy.
• Somatic and visceral: bodily sensations, in schizophrenia and depression.
• Complex phenomena: musical hallucinations in hearing loss, command hallucinations, and presence hallucinations in Parkinson disease.

Classification by cause

• Primary psychotic disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, delusional disorder).
• Mood disorders with psychotic features, posttraumatic stress disorder, and severe personality disorder.
• Delirium and dementia, especially Lewy body dementia.
• Epilepsy, stroke, tumour, migraine, and other structural lesions.
• Substance intoxication and withdrawal, and drug adverse effects.
• Metabolic, infectious, autoimmune and endocrine disorders.
• Sensory impairment (vision, hearing), sleep deprivation, bereavement and extreme stress.
• Cultural and religious experiences, normal variant (hearing a deceased relative after bereavement), and hypnagogic experiences.

Epidemiology. Hallucinations occur at some time in 5 to 15% of the general population, mostly without disorder. Auditory hallucinations occur in about 70% of people with schizophrenia. Visual hallucinations occur in up to 80% of people with Lewy body dementia and a large share of those with advanced Parkinson disease. Charles Bonnet syndrome affects up to a third of people with severe visual loss.

Mechanisms.

• Dopamine excess in the mesolimbic tract and altered glutamate (NMDA) signalling in primary psychosis.
• Cholinergic deficiency and visual cortex dysfunction in Lewy body disease and Parkinson disease.
• Release phenomena in deafferented sensory cortex (Charles Bonnet syndrome, musical hallucinations).
• Ictal activation of temporal cortex.
• Serotonin 5-HT2A agonism for hallucinogens.

Key distinctions. Fluctuating attention and disorientation with visual hallucinations suggest delirium. Well formed visual hallucinations of people or animals with parkinsonism and fluctuating cognition suggest Lewy body dementia. Voices commenting or conversing in a clear sensorium suggest schizophrenia. Simple recurring hallucinations of smell or taste with brief loss of awareness suggest focal seizures. Complex visual hallucinations with insight in a person with poor vision suggest Charles Bonnet syndrome.

History

• The experience: modality, content, frequency, duration, onset, whether voices are inside or outside the head, one or more voices, familiar or unfamiliar, commenting, commanding or threatening, ability to ignore or resist, and effect on behaviour.
• Command hallucinations: content (to harm self or others), compliance, ability to resist, and previous acting on commands.
• Insight and beliefs about the experience (explanations, delusions, religious or cultural interpretation).
• Onset and course: acute or gradual, episodic or continuous, relation to sleep, illness, stress, bereavement, substances, medication changes and head injury.
• Psychiatric symptoms: delusions, disorganised speech, negative symptoms, mood symptoms, mania, depression, trauma and flashbacks, and suicidal thoughts.
• Cognitive symptoms: memory loss, confusion, fluctuating alertness, sleep disturbance, falls, and visual spatial problems.
• Neurological symptoms: headache, seizures, aura, weakness, tremor, rigidity, smell loss, REM sleep behaviour disorder, and visual or hearing loss.
• Medical history: epilepsy, stroke, Parkinson disease, dementia, migraine, HIV, syphilis, thyroid disease, kidney or liver disease, autoimmune disease, and cancer.
• Substances: alcohol (amount, last drink, withdrawal), cannabis (including high potency and synthetic), stimulants, hallucinogens, ketamine, phencyclidine, opioids, benzodiazepines, khat, and new psychoactive substances.
• Drugs: levodopa and dopamine agonists (pramipexole, ropinirole), amantadine, anticholinergics, corticosteroids, antiepileptics (levetiracetam, topiramate, perampanel), fluoroquinolones, isoniazid, cycloserine, mefloquine, efavirenz, baclofen, opioids, tramadol, zolpidem, montelukast, beta blockers, digoxin, ifosfamide, and interferon.
• Sensory function: vision and hearing loss, cataract, macular degeneration, glaucoma, tinnitus, ear disease.
• Family history of psychosis, bipolar disorder, dementia, and epilepsy. Developmental and trauma history.
• Functional impact, risk to self and others, and social supports.

Examination

• Appearance and behaviour: responding to unseen stimuli, muttering, guarded or suspicious manner.
• Level of arousal, attention (months of the year backwards, serial sevens), orientation, and the 4AT delirium screen (score of 4 or more is possible delirium).
• Mental state: mood, thought form and content (delusions of reference, control, persecution), perception, insight, and risk.
• Vital signs: temperature, pulse, blood pressure, respiratory rate, oxygen saturation, and glucose.
• Neurological examination: gait, tremor, rigidity, bradykinesia, cranial nerves, visual fields, fundi (papilloedema), focal signs, reflexes, nystagmus, and ataxia.
• Sensory examination: visual acuity, visual fields, otoscopy and whisper test.
• General: signs of alcohol use or withdrawal (tremor, sweating), injection marks, thyroid, signs of infection, pallor, jaundice, rash, and skin lesions (delusional infestation).
• Bedside tests: glucose, urine dipstick, Montreal Cognitive Assessment or Mini-Mental State Examination, clock drawing, and PHQ-9.

Red flags

• Acute confusion with fluctuating alertness (delirium).
• Command hallucinations to harm self or others, with history of acting on them.
• Suicidal intent or violence, or inability to care for self.
• Hallucinations of smell or taste, aura, tongue bite, post event confusion, or stereotyped events (seizures).
• New headache, focal neurological signs, papilloedema, or personality change (intracranial mass, stroke, encephalitis).
• Fever, meningism, rash, or immunosuppression, including HIV and recent travel (CNS infection, cerebral malaria).
• Alcohol withdrawal with tremor, sweating, autonomic instability and visual or tactile hallucinations (delirium tremens).
• Recent start or change of a dopaminergic, anticholinergic, corticosteroid or antiepileptic drug.
• Parkinsonism, fluctuating cognition, or REM sleep behaviour disorder (Lewy body disease), because antipsychotics may cause severe reactions.
• Onset after age 40 years without psychiatric history, or abrupt change in a previously well person.
• Postpartum onset with confusion or mood change (postpartum psychosis).
• Hallucinations with psychosis in a young adult with catatonia, seizures, dyskinesias or autonomic features (anti-NMDA receptor encephalitis).
• Visual hallucinations in a person with severe visual loss, for safety and mood assessment.

Special groups

• Children and adolescents: transient hallucinations can be normal in young children, and associated with trauma, anxiety and sleep problems. Persistent hallucinations need specialist assessment. Use age specific doses.
• Pregnancy and postpartum: consider postpartum psychosis, delirium, eclampsia and thyroid disease. Specialist care.
• Older adults: delirium, dementia, Parkinson disease, depression, drugs and sensory loss are leading causes. Use low doses and avoid anticholinergics.
• Medical inpatients and intensive care: delirium, sleep deprivation and drugs.
• Region specific: culturally normal experiences (spirit voices, ancestors), trauma in conflict affected populations, cerebral malaria, neurocysticercosis, trypanosomiasis, HIV related disorders, khat and traditional hallucinogens.

Primary psychiatric

• Schizophrenia, schizophreniform disorder and schizoaffective disorder.
• Brief psychotic disorder and delusional disorder.
• Bipolar disorder with psychotic features (mania, depression).
• Major depression with psychotic features.
• Posttraumatic stress disorder (flashbacks, voices).
• Dissociative disorders, borderline personality disorder (transient psychosis) and conversion.
• Severe obsessive compulsive disorder.
• Postpartum psychosis.
• Factitious and malingered hallucinations (rare).

Neurological

• Delirium (any cause).
• Dementia with Lewy bodies and Parkinson disease psychosis.
• Alzheimer disease, vascular dementia and frontotemporal dementia.
• Temporal and occipital lobe epilepsy, and postictal psychosis.
• Migraine with aura and Alice in Wonderland syndrome.
• Stroke (peduncular hallucinosis, thalamic, occipital), brain tumour, traumatic brain injury.
• Narcolepsy (hypnagogic hallucinations) and sleep paralysis.
• Charles Bonnet syndrome and musical hallucinations in hearing loss.
• Autoimmune encephalitis (anti-NMDA receptor, limbic encephalitis).
• Creutzfeldt-Jakob disease, Huntington disease and multiple sclerosis.
• Normal pressure hydrocephalus.

Substance and drug related

• Alcohol withdrawal, alcoholic hallucinosis and delirium tremens.
• Cannabis and synthetic cannabinoids, cocaine, amphetamines and methamphetamine, khat and cathinones.
• Lysergic acid diethylamide, psilocybin, mescaline, ketamine, phencyclidine and dextromethorphan.
• Benzodiazepine and barbiturate withdrawal.
• Drug induced (levodopa, dopamine agonists, amantadine, anticholinergics, corticosteroids, levetiracetam, topiramate, fluoroquinolones, isoniazid, cycloserine, mefloquine, efavirenz, baclofen withdrawal, tramadol, zolpidem).

Metabolic, endocrine, infective and systemic

• Hypoglycaemia, hyponatraemia, hypercalcaemia, uraemia, hepatic encephalopathy and hypoxia.
• Hyperthyroidism and thyroid storm; hypothyroidism (myxoedema madness).
• Vitamin B12, thiamine (Wernicke encephalopathy) and niacin deficiency.
• Cushing syndrome and Addison disease.
• Acute intermittent porphyria and Wilson disease.
• Systemic lupus erythematosus and other vasculitis.
• HIV, neurosyphilis, herpes simplex and other encephalitis, tuberculous meningitis, cerebral malaria, neurocysticercosis, trypanosomiasis and sepsis.
• Eclampsia.

Sensory and physiological

• Visual impairment (cataract, macular degeneration, retinal disease), hearing loss and tinnitus.
• Sleep deprivation and sleep related hallucinations.
• Bereavement hallucinations and grief.
• Sensory deprivation and isolation (including intensive care).
• Normal variants and cultural experiences.

Step 1. Safety and delirium. Assess risk to self and others, command hallucinations and ability to resist. Screen for delirium (4AT, Confusion Assessment Method) in every patient with new hallucinations, particularly those with visual or tactile phenomena. Delirium requires urgent medical work up.

Step 2. Psychiatric and neurological history. Characterise the hallucinations, associated symptoms, onset, course, substances and drugs, family history, and sensory loss. Establish the likely diagnosis (primary psychosis, mood disorder, organic condition). Use the Positive and Negative Syndrome Scale, Psychotic Symptom Rating Scales or the Brief Psychiatric Rating Scale to quantify psychosis in specialist settings.

Step 3. First line tests

• Capillary glucose, oxygen saturation, temperature, and 12 lead ECG (before antipsychotics).
• Full blood count, urea, creatinine, electrolytes (sodium), calcium, magnesium, liver tests, CRP, and thyroid stimulating hormone.
• Vitamin B12, folate, and HIV and syphilis serology.
• Urinalysis and urine or serum drug screen, and blood alcohol.
• Pregnancy test in women of reproductive age.
• Baseline metabolic assessment before antipsychotics: weight, body mass index, waist circumference, blood pressure, fasting glucose or HbA1c, lipid profile, and prolactin.

Step 4. Targeted tests

• CT or MRI brain for first episode psychosis, onset after age 40 years, focal signs, delirium without a clear cause, seizures, head injury, headache, or atypical features.
• Electroencephalogram for suspected seizures, encephalopathy or encephalitis.
• Lumbar puncture (cells, protein, glucose, oligoclonal bands, herpes simplex virus PCR, syphilis and autoimmune antibodies) and serum autoantibodies (NMDA receptor, LGI1, voltage gated potassium channel complex, anti-nuclear antibody) when encephalitis is suspected.
• Ammonia, porphyria screen, caeruloplasmin and slit lamp (Wilson disease in young adults), copper, heavy metals, cortisol, and ANA as directed.
• Toxicology screen for novel substances in unclear cases.
• Formal cognitive testing, DaTscan or polysomnography for suspected Lewy body disease and REM sleep behaviour disorder.
• Ophthalmology and audiology for visual and hearing loss.
• Polysomnography for narcolepsy features.

Step 5. Interpretation. In a clear sensorium with typical auditory hallucinations and thought disorder in a young adult, a normal screen supports primary psychosis. Abnormal results require treatment of the cause first. Antipsychotic response does not exclude organic causes. Persistence after treatment of the cause suggests a primary disorder.

Limits. Hallucinations are reported subjectively and may be concealed. No test confirms a primary psychotic disorder. Drug screens miss many novel substances.

Immediate

• Ensure safety of the patient and others, in a calm, low stimulation setting. Explain, avoid arguing about the reality of the experience, and acknowledge that it feels real to them.
• Treat medical emergencies: delirium (find and treat cause), hypoglycaemia, hypoxia, alcohol withdrawal, seizures, intoxication and infection.
• Command hallucinations with risk: continuous observation, urgent specialist assessment, and admission if risk cannot be managed in the community.
• Short term sedation for agitation: lorazepam 1 to 2 mg orally, or olanzapine 5 to 10 mg orally (avoid combined benzodiazepine and intramuscular olanzapine within 1 hour).

Treatment of the cause

• Delirium: treat precipitants, review drugs, correct metabolic derangement, orientation and sleep measures. For distress or danger, haloperidol 0.5 to 1 mg orally or intramuscularly (maximum 5 mg daily in older adults), or olanzapine 2.5 mg, for the shortest time. Avoid benzodiazepines except in alcohol or sedative withdrawal.
• Alcohol withdrawal and hallucinosis: chlordiazepoxide 20 to 30 mg orally every 6 hours reducing over 5 to 7 days (or diazepam 10 to 20 mg every 6 hours reducing).
• Give thiamine 200 to 500 mg intravenously three times daily for 3 to 5 days when Wernicke encephalopathy is possible, then 100 mg orally daily. Replace magnesium and potassium.
• Drug induced: stop or reduce the offending agent where possible (for example reduce levodopa and dopamine agonists, stop anticholinergics, review steroids, change antiepileptic).
• Substance induced psychosis: abstinence, supportive care and short term antipsychotic treatment if needed. Review at 4 weeks to detect persistent psychosis.
• Epilepsy: antiepileptic treatment by seizure type, such as lamotrigine 25 mg daily for 2 weeks, 50 mg daily for 2 weeks, then increasing by 50 mg every 1 to 2 weeks to a usual 100 to 200 mg daily (maximum 400 mg; halve the schedule with valproate), avoiding levetiracetam when psychiatric adverse effects occur.
• Infection, metabolic and endocrine disease: treat the cause. Autoimmune encephalitis: methylprednisolone 1 g intravenously daily for 3 to 5 days, immunoglobulin 0.4 g/kg daily for 5 days or plasma exchange, and tumour search, under specialist care.
• Sensory loss: correct hearing and vision (cataract surgery, hearing aids).
• Charles Bonnet syndrome and bereavement hallucinations: reassurance, education, treatment of visual loss, and improved lighting. Drugs are rarely needed.
• Narcolepsy and sleep related hallucinations: treat narcolepsy, regularise sleep.

Primary psychotic disorders (first episode and relapse)

• Early referral to early intervention in psychosis services.
• Choose an antipsychotic with the patient, and start low.
• Olanzapine 5 to 10 mg orally once daily at night (usual 10 to 20 mg, maximum 20 mg).
• Risperidone 1 to 2 mg daily increased to 2 to 6 mg (maximum 6 mg).
• Aripiprazole 10 to 15 mg once daily increased to 15 to 30 mg (maximum 30 mg).
• Amisulpride 100 to 400 mg increased to 400 to 800 mg daily (maximum 1200 mg; renal adjustment, QT effect).
• Quetiapine 50 mg twice daily on day 1 increasing to 300 to 800 mg daily in divided doses.
• Haloperidol 2 to 5 mg daily (maximum 20 mg), which causes more movement disorder.
• Review response at 2 to 4 weeks (hallucinations often reduce within days to weeks). Allow 4 to 6 weeks at an adequate dose before switching. Continue for at least 1 to 2 years after a first episode, and longer after relapse.
• Treatment resistant psychosis (no response to two antipsychotics, each for 6 weeks at adequate dose): clozapine 12.5 mg once or twice on day 1, increasing by 25 to 50 mg daily to 300 to 450 mg (maximum 900 mg).
• Monitor the blood count (weekly for 18 weeks, then fortnightly to 1 year, then monthly). Monitor for myocarditis (troponin and CRP weekly in the first 4 weeks), constipation, sedation, hypersalivation, seizures and metabolic effects.
• Long acting injectable antipsychotics when adherence is poor: paliperidone palmitate 150 mg intramuscularly in the deltoid on day 1 then 100 mg on day 8, then 75 to 150 mg monthly.
• Aripiprazole monohydrate 400 mg intramuscularly monthly (with oral aripiprazole for the first 14 days).
• Risperidone microspheres 25 mg every 2 weeks (with oral risperidone for 3 weeks), increased to 50 mg every 2 weeks.
• Psychological and psychosocial treatment: cognitive behavioural therapy for psychosis (at least 16 sessions), family intervention, supported employment, and treatment of substance use.
• Monitoring for adverse effects: weight, waist, blood pressure, glucose, lipids, prolactin, ECG, extrapyramidal symptoms (acute dystonia: procyclidine 5 to 10 mg intramuscularly; parkinsonism: dose reduction; akathisia: propranolol 10 to 20 mg two or three times daily), and tardive dyskinesia (Abnormal Involuntary Movement Scale).
• Mood disorders with psychotic features: antidepressant with antipsychotic (for example sertraline 100 mg with olanzapine 5 to 10 mg), or electroconvulsive therapy. Mania: olanzapine 10 to 15 mg, risperidone 2 to 4 mg, quetiapine 400 to 800 mg, or lithium.
• Posttraumatic stress disorder with hallucinations: trauma focused therapy and sertraline, with prazosin 1 mg at night increased to 3 to 15 mg for nightmares if needed.

Neurodegenerative disease

• Dementia with Lewy bodies and Parkinson disease dementia: rivastigmine 1.5 mg orally twice daily, increased every 2 to 4 weeks by 1.5 mg twice daily to 3 to 6 mg twice daily. Alternatively use the patch: 4.6 mg/24 hours increased to 9.5 mg/24 hours after 4 weeks, and to 13.3 mg/24 hours if needed.
• Alternatively, donepezil 5 mg daily increased to 10 mg.
• Reduce dopaminergic drugs and stop anticholinergics, treat infection and pain.
• If antipsychotics are needed for distressing psychosis in Parkinson disease: quetiapine 12.5 to 25 mg at night increased slowly to 50 to 100 mg.
• Alternatively, pimavanserin 34 mg once daily (where available).
• Alternatively, low dose clozapine 6.25 to 12.5 mg at night increased to 25 to 50 mg with blood monitoring.
• Avoid haloperidol, risperidone and olanzapine (severe sensitivity reactions and worsened motor function).
• Alzheimer disease and other dementias: treat reversible causes, use nonpharmacological measures, and consider risperidone 0.25 mg twice daily (maximum 2 mg daily) only for severe distress or danger, for the shortest time, with consent discussion of the stroke and mortality risks.

Special populations

• Pregnancy and breastfeeding: specialist care. Choose olanzapine, quetiapine or haloperidol where possible, avoid valproate, and monitor glucose.
• Children and adolescents: specialist treatment. Risperidone 0.25 to 0.5 mg orally at night, increased slowly to 2 to 4 mg (maximum 6 mg in adolescents), or aripiprazole 2 mg increased to 10 to 15 mg, with metabolic monitoring.
• Older adults: halve starting doses (risperidone 0.25 to 0.5 mg, olanzapine 2.5 mg), monitor falls, sodium and ECG.
• Kidney and liver impairment: adjust amisulpride (halve at creatinine clearance 30 to 60 mL/min, a third at 10 to 30 mL/min, avoid under 10 mL/min), start low with olanzapine and risperidone.
• QT prolonging drugs: check ECG and electrolytes (QTc over 500 ms or an increase over 60 ms is a reason to stop).

Monitoring. Frequency and content of hallucinations, risk, adherence, adverse effects, metabolic indices at baseline, 6 weeks, 3 months and annually, prolactin, ECG, and substance use. Review in 1 to 2 weeks after starting, then monthly until stable.

Referral and escalation. Psychiatry the same day for command hallucinations, suicidal or violent risk, mania or severe psychosis. Early intervention in psychosis services for first episodes. Neurology for epilepsy, encephalitis, movement disorders and dementia. Ophthalmology and audiology for sensory loss. Old age psychiatry for hallucinations in older adults. Addiction services for substance related psychosis.

Admission criteria. Risk to self or others, command hallucinations with intent, severe agitation, delirium requiring inpatient care, inability to eat or drink, severe withdrawal, catatonia, and failure of community care. Use mental health legislation when needed.

Discharge and follow up. Written plan and crisis numbers, medication education, early review in 1 to 2 weeks, family involvement, and relapse signature. Safety net advice: return for command hallucinations, thoughts of harm, confusion, severe agitation, fever, seizure, stiffness or tremor after starting an antipsychotic, sore throat or fever on clozapine, or stopping medicines.