Delusions and paranoia

A delusion is a fixed, false belief that is held with conviction despite clear evidence to the contrary and that is not accounted for by the person's culture, education or religion. Paranoia is suspicion, mistrust or belief that others intend harm, ranging from mild mistrust to persecutory delusions.

Like hallucinations, delusions are a symptom with many causes: primary psychosis, mood disorders, delirium and dementia, neurological disease, substances, drugs, and medical illness. The first tasks are risk assessment (to the patient and to the people involved in the belief), exclusion of delirium and organic causes, and engagement, because most patients lack insight and refuse treatment.

Definitions

• Delusion: a belief that is false, fixed, incorrigible, and out of keeping with the person's background. Overvalued ideas are strongly held but not fixed and not entirely implausible.
• Paranoid ideation: suspiciousness without full conviction.
• Primary delusion: arises fully formed (delusional perception, delusional mood). Secondary delusions arise from another abnormal experience (mood, hallucination).
• Delusional misidentification: Capgras (a familiar person replaced by an impostor), Fregoli (strangers are a persecutor in disguise), intermetamorphosis, and mirrored self misidentification.

Types of delusion

• Persecutory (being followed, poisoned, spied on, plotted against).
• Reference (neutral events have special meaning for the person).
• Control and passivity (thoughts inserted, withdrawn or broadcast; actions controlled by others).
• Grandiose (special powers, identity or wealth).
• Erotomanic (a person of higher status is in love with the patient).
• Jealousy (Othello syndrome: delusional infidelity of a partner), with a high risk of violence.
• Somatic (a bodily defect or disease), including delusional infestation (Ekbom syndrome, delusional parasitosis).
• Nihilistic and Cotard (the body or world is dead or does not exist), and delusions of guilt, poverty and hypochondriasis in psychotic depression.
• Mixed or unspecified delusions, and shared delusions (folie à deux).

Classification by disorder

• Schizophrenia, schizophreniform and schizoaffective disorders.
• Delusional disorder (one or more delusions lasting at least 1 month, without prominent hallucinations or disorganised behaviour, with functioning not markedly impaired outside the delusion).
• Brief psychotic disorder (1 day to 1 month).
• Mood disorders with psychotic features (mood congruent delusions in mania and depression).
• Psychotic disorder due to a medical condition, substance or medication.
• Delirium and dementia related delusions (theft, infidelity, abandonment, phantom boarder).
• Late onset schizophrenia like psychosis.
• Paranoid personality disorder (distrust without fixed delusions).
• Posttraumatic and depressive conditions with paranoid ideation.

Epidemiology. Delusional disorder affects about 0.2% of the population, with onset in middle age. Schizophrenia affects about 0.5 to 1% of the population, with onset in late adolescence and early adulthood. Delusions affect up to 30 to 40% of people with Alzheimer disease at some time and more than 50% of those with Lewy body dementia. Paranoid thoughts occur in about 10 to 15% of the general population at some time.

Mechanisms. Aberrant salience attribution from dopamine dysregulation, glutamatergic dysfunction, frontotemporal dysfunction, cholinergic deficiency in Lewy body disease, social isolation, trauma and threat anticipation, reasoning biases (jumping to conclusions) and sensory impairment.

Key distinctions. Delusions in a clouded sensorium with fluctuating attention suggest delirium. Bizarre delusions with hallucinations and thought disorder suggest schizophrenia. A single non-bizarre delusion with preserved function suggests delusional disorder. Mood congruent delusions with elevated or depressed mood suggest a mood disorder. A first presentation of delusions in an older adult needs a full organic work up.

History

• Content, onset, duration, conviction (percentage certainty), preoccupation, distress, how the belief is explained, and effect on behaviour (avoidance, safety behaviours, confrontation, stalking, complaints to police, self neglect, refusal to eat, litigation).
• Risk: threats, violence, weapons, targets of the delusion, intent to harm self or others, jealousy of a partner, harassment, and prior offences. Whether the patient has acted on delusions.
• Hallucinations, disorganised speech and behaviour, negative symptoms, catatonia, mood symptoms (mania, depression), and cognition.
• Insight and willingness to engage. Capacity to consent to treatment.
• Course: abrupt (delirium, drug, brief psychosis) or gradual (schizophrenia, delusional disorder, dementia), and relation to life events.
• Substances: cannabis (high potency), stimulants (amphetamine, methamphetamine, cocaine, khat), alcohol, hallucinogens, ketamine, new psychoactive substances, and withdrawal.
• Drugs: corticosteroids, levodopa and dopamine agonists, anticholinergics, stimulants, antiepileptics, isoniazid, efavirenz, anabolic steroids, antimalarials (mefloquine), antimicrobials (fluoroquinolones), and recent changes.
• Medical history: epilepsy, head injury, stroke, dementia, Parkinson disease, Huntington disease, HIV, syphilis, thyroid and adrenal disease, vitamin B12 deficiency, autoimmune disease, hearing and vision loss, and cancer.
• Psychiatric history, family history of psychosis, personality, trauma and developmental history.
• Social circumstances: isolation, migration, discrimination, bereavement, unemployment, housing, relationships and cultural beliefs (to distinguish from culturally normative beliefs).
• Collateral history from family, carers, neighbours and police.

Examination

• Appearance, grooming, level of arousal, and attention (months backwards).
• Mental state: mood, thought form and content, nature and conviction of the delusion, systematisation, hallucinations, insight, cognition, and risk.
• Physical: vital signs, signs of intoxication or withdrawal, thyroid, neurological examination (parkinsonism, cranial nerves, visual fields, gait, focal signs, frontal release signs), eye and ear examination for sensory loss.
• Skin examination in delusional infestation (excoriations, specimen collection in a matchbox or bag, digging wounds).
• Bedside tests: 4AT, Montreal Cognitive Assessment, glucose, urinalysis, and PHQ-9.
• Rating tools: the Psychotic Symptom Rating Scales (Delusions subscale), the Peters Delusions Inventory, and the Brief Psychiatric Rating Scale. The Paranoid Thoughts Scale is used in research and clinic.

Red flags

• Delusions of persecution, jealousy or erotomania with threats, stalking, weapons or violence, or a named target.
• Delusions of poisoning leading to refusal of food, fluids or medicines.
• Nihilistic or guilt delusions with suicidal thoughts (psychotic depression).
• Delirium or fluctuating consciousness, new confusion or visual hallucinations.
• First onset after age 40 years or abrupt change in behaviour in a previously well person.
• Focal neurological signs, headache, seizures, head injury, or papilloedema.
• Fever, immunosuppression, HIV, syphilis risk, or recent travel.
• Delusions with catatonic signs, dyskinesias, seizures, autonomic instability, or hypoventilation (anti-NMDA receptor encephalitis).
• Parkinsonism with delusions (Lewy body disease: avoid typical antipsychotics).
• Mania with grandiose delusions and no sleep.
• Postpartum onset, or delusions involving the infant (risk to the child).
• Young adult with delusions and liver disease or movement disorder (Wilson disease).
• Starting corticosteroids, dopamine agonists or stimulants.
• Delusions that others (a child, partner or carer) are impostors, or shared delusions involving a vulnerable person.

Special groups

• Children and adolescents: specialist assessment, early intervention, and exclusion of trauma, autism and substance use. Use age specific doses.
• Pregnancy and postpartum: consider postpartum psychosis, delirium, thyroid disease and eclampsia. Specialist care.
• Older adults: delirium, dementia, depression, sensory loss, isolation and drugs. Low doses, caution with antipsychotic risks.
• Migrants and minority groups: distinguish cultural and religious beliefs from delusions, use interpreters, and consider trauma.
• Region specific: beliefs in witchcraft and possession are culturally shaped. Assess whether the belief is shared by the community and whether there is distress, impairment or change from baseline.

Primary psychotic and mood disorders

• Schizophrenia, schizophreniform and schizoaffective disorder.
• Delusional disorder (persecutory, jealous, erotomanic, grandiose, somatic).
• Brief psychotic disorder.
• Bipolar disorder (mania with psychosis, depression with psychosis).
• Major depression with psychotic features and Cotard syndrome.
• Postpartum psychosis.
• Late onset schizophrenia like psychosis.
• Shared psychotic disorder (folie à deux).
• Paranoid, schizotypal and borderline personality disorders.
• Posttraumatic stress disorder and obsessive compulsive disorder (overvalued ideas).
• Autism spectrum disorder (fixed ideas and misinterpretation).
• Body dysmorphic disorder and illness anxiety disorder (non-delusional variants).

Neurological and neurodegenerative

• Delirium.
• Alzheimer disease, vascular dementia, frontotemporal dementia, Lewy body dementia and Parkinson disease dementia.
• Huntington disease and multiple sclerosis.
• Temporal lobe epilepsy and postictal psychosis.
• Stroke (right hemisphere, frontal), brain tumour and traumatic brain injury.
• Autoimmune encephalitis, limbic encephalitis and neurosyphilis.
• Normal pressure hydrocephalus and Creutzfeldt-Jakob disease.
• Reduplicative paramnesia and misidentification syndromes.

Substance and drug related

• Cannabis and synthetic cannabinoid psychosis.
• Stimulant psychosis (amphetamine, methamphetamine, cocaine, khat).
• Alcohol related psychosis, withdrawal and Wernicke-Korsakoff syndrome.
• Hallucinogens, ketamine, and anabolic steroids.
• Drug induced (corticosteroids, levodopa, dopamine agonists, anticholinergics, isoniazid, efavirenz, mefloquine, fluoroquinolones, antiepileptics, interferon).

Medical causes

• Hyperthyroidism, hypothyroidism, Cushing syndrome and hyperparathyroidism.
• Vitamin B12, thiamine and folate deficiency.
• Hepatic encephalopathy, uraemia, hyponatraemia and hypoglycaemia.
• Systemic lupus erythematosus and other autoimmune disease.
• HIV related neurocognitive disorders and opportunistic infection.
• Wilson disease and acute intermittent porphyria.
• Sensory impairment (hearing, vision) and chronic pain.
• Sleep deprivation.

Special syndromes and mimics

• Delusional infestation (primary, or secondary to cocaine, amphetamine, neuropathy, vitamin B12 deficiency, scabies and true infestation).
• Overvalued ideas, extremist or conspiracy beliefs (shared by a group).
• Cultural and religious beliefs.
• Reality based mistrust (abuse, stalking, surveillance, racism).
• Factitious disorder and malingering.

Step 1. Risk and capacity. Assess risk to self, to the people involved in the belief and to others, with documented threats, weapons, history of violence and willingness to act. Establish capacity for treatment decisions. Obtain collateral history.

Step 2. Screen for delirium and organic causes. Use the 4AT or Confusion Assessment Method in all patients with new delusions. In older adults, any new delusional belief is organic until proven otherwise. Check drugs and substances.

Step 3. Psychiatric diagnosis. Use diagnostic criteria. Characterise the delusion (systematised, bizarre, mood congruent), associated hallucinations, thought disorder, negative symptoms, mood episodes, and duration (under 1 month: brief psychotic disorder; 1 to 6 months: schizophreniform disorder; over 6 months: schizophrenia; delusions only for at least 1 month: delusional disorder). Judge cultural plausibility with an informant or cultural interpreter.

Step 4. First line tests

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

Step 5. Targeted tests

• CT or MRI brain: first episode, onset after age 40 years, focal signs, cognitive impairment, head injury, headache or atypical features.
• Electroencephalogram for seizure features or encephalopathy.
• Lumbar puncture and serum and CSF autoantibodies (NMDA receptor, LGI1, CASPR2) for subacute onset with seizures, movement disorder, memory loss or autonomic features.
• Caeruloplasmin and slit lamp examination in young adults, cortisol, ANA, ammonia, porphyria screen, and heavy metals directed by clinical features.
• Neuropsychological testing and dementia work up for older adults.
• Skin examination, specimen review and dermatology liaison in delusional infestation, including scabies, thyroid and B12 checks.
• Audiology and ophthalmology for sensory loss.

Interpretation. A clear sensorium, normal investigations, and typical history support primary psychosis or delusional disorder. A fixed single non-bizarre delusion with otherwise intact function suggests delusional disorder. Persistence after treating organic contributors suggests a primary disorder. A negative toxicology screen does not exclude substance causes.

Limits. Insight is often absent, so history may need collateral input. Cultural interpretation requires care. Delusions may be concealed. No test confirms delusional disorder.

Immediate

• Safety: protect the patient and those named in the delusion. Warn identified victims when duty and local law require it. Use a calm, nonconfrontational approach, avoid colluding with or arguing about the belief, acknowledge the distress, and focus on what the patient feels and wants.
• Treat medical causes and delirium. Withdraw offending drugs where possible.
• Agitation or danger: de-escalation first, then lorazepam 1 to 2 mg orally or olanzapine 5 to 10 mg orally (intramuscular olanzapine not within 1 hour of a parenteral benzodiazepine), or haloperidol 5 mg with lorazepam 1 to 2 mg, using local emergency doses.
• Refusal of food, fluids or medicines because of the delusion: urgent assessment, capacity, and use of mental health legislation if needed.

Therapeutic engagement

• Build a therapeutic alliance over several contacts. Explore the person's concerns and offer help for the distress, sleep, anxiety and consequences, without needing agreement about the belief.
• Cognitive behavioural therapy for psychosis (at least 16 sessions), metacognitive training, and family intervention.
• Address substance use, isolation, hearing and vision loss, and social problems.

Antipsychotic treatment (primary psychosis, delusional disorder, mood disorder with psychosis, and selected organic psychosis)

• Discuss options and side effects, and start low. Review at 1 to 2 weeks for tolerability and at 4 to 6 weeks for response, with an adequate dose and duration before switching.
• Risperidone 1 mg orally daily (or 0.5 mg twice daily), increased by 1 mg every 2 to 3 days to 2 to 4 mg daily, maximum 6 mg daily (maximum 4 mg in practice for delusional disorder). Prolactin rise and extrapyramidal effects.
• Olanzapine 5 to 10 mg orally at night, usual 10 to 20 mg, maximum 20 mg. Weight gain, glucose and lipid effects.
• Aripiprazole 10 to 15 mg orally once daily, up to 30 mg. Akathisia, insomnia.
• Amisulpride 100 to 200 mg twice daily, up to 800 mg daily (maximum 1200 mg). Adjust at creatinine clearance under 60 mL/min, and check QT.
• Quetiapine 50 mg twice daily, increased to 300 to 800 mg daily in divided doses. Sedation, orthostatic hypotension, metabolic effects.
• Haloperidol 2 to 5 mg orally daily, up to 10 mg (maximum 20 mg), with high movement disorder risk, and anticholinergic cover only if needed.
• Long acting injectable preparations are used for poor adherence or relapse. Paliperidone palmitate: 150 mg intramuscularly on day 1 and 100 mg on day 8, then monthly 75 to 150 mg.
• Aripiprazole monohydrate 400 mg monthly (with 14 days of oral cover).
• Risperidone microspheres 25 mg every 2 weeks (with 3 weeks of oral cover).
• Flupentixol decanoate 20 mg test dose, then 20 to 40 mg every 2 to 4 weeks.
• Delusional disorder responds less well than schizophrenia, and benefit may take 6 to 12 weeks. Risperidone, olanzapine or aripiprazole are used, with pimozide 1 to 2 mg in specialist care for delusional infestation (ECG and QT monitoring, interactions with CYP2D6 and CYP3A4 inhibitors).
• Treatment resistant disease (no response to two antipsychotics, each at adequate dose for 6 weeks): clozapine 12.5 mg once or twice on day 1, increasing by 25 to 50 mg daily to 300 to 450 mg daily (maximum 900 mg).
• On clozapine, monitor the blood count (weekly for 18 weeks, then fortnightly to 1 year, then monthly). Monitor also for myocarditis, constipation, hypersalivation, seizures and metabolic effects.
• Psychotic depression: sertraline 100 to 200 mg or venlafaxine with olanzapine 5 to 15 mg or quetiapine, or electroconvulsive therapy (rapid and effective, especially with food refusal, catatonia or high suicide risk). Mania: olanzapine 10 to 15 mg, risperidone 2 to 4 mg, or lithium.
• Delusional infestation: exclude true infestation (examine specimens, treat scabies if present), correct vitamin B12 deficiency, thyroid disease and substance use, and offer risperidone 0.5 to 1 mg increased to 2 to 3 mg or aripiprazole 5 to 10 mg, with supportive follow up. Avoid unnecessary dermatological interventions that reinforce the belief.
• Duration: continue at least 1 to 2 years after a first episode, and longer after relapses, then taper slowly with close review.

Delirium and dementia related delusions

• Treat the cause of delirium. For distressing delusions or danger, haloperidol 0.5 to 1 mg orally or intramuscularly (maximum 5 mg daily in older adults), or olanzapine 2.5 mg, for days only.
• Dementia: reassure, correct sensory loss, simplify surroundings, treat pain and infection, reduce anticholinergic load, and avoid contradiction.
• Cholinesterase inhibitors (rivastigmine, donepezil) are first for Lewy body and Parkinson disease dementia.
• Risperidone 0.25 mg twice daily (maximum 2 mg daily) only for severe distress or danger, for the shortest time, with review at 6 weeks and discussion of the stroke and mortality risks.
• Lewy body disease and Parkinson disease: avoid haloperidol, risperidone and olanzapine. Use quetiapine 12.5 to 25 mg at night, pimavanserin 34 mg daily (where available), or clozapine 6.25 to 25 mg at night with blood monitoring.

Substance induced psychosis. Abstinence, supportive care and a short course of an antipsychotic (olanzapine 5 to 10 mg or risperidone 1 to 2 mg). Symptoms usually settle within days to 4 weeks after stopping the substance. Persistence suggests a primary psychotic disorder.

Other causes. Autoimmune encephalitis: methylprednisolone 1 g intravenously daily for 3 to 5 days, immunoglobulin 0.4 g/kg daily for 5 days, plasma exchange, and tumour search. Neurosyphilis: benzylpenicillin 18 to 24 million units daily intravenously for 10 to 14 days. HIV: start antiretroviral therapy. Vitamin B12 deficiency: hydroxocobalamin 1 mg intramuscularly on alternate days for 2 weeks, then every 3 months. Thyroid disease: treat the thyroid disorder. Wilson disease: specialist chelation. Special populations

• Pregnancy and breastfeeding: olanzapine, quetiapine or haloperidol are the usual choices, with specialist care. Avoid valproate and carbamazepine. Postpartum psychosis is an emergency requiring admission, ideally to a mother and baby unit.
• Children and adolescents: specialist early intervention teams. Risperidone 0.25 to 0.5 mg at night increased slowly to 2 to 4 mg, or aripiprazole 2 mg increased to 10 to 15 mg, with metabolic monitoring.
• Older adults: halve doses (risperidone 0.25 to 1 mg, olanzapine 2.5 to 5 mg), monitor falls, sodium, ECG and glucose, and review the need regularly.
• Kidney and liver impairment: reduce amisulpride and paliperidone in renal impairment, and start low with olanzapine and risperidone in hepatic impairment.
• QT concern: check ECG and electrolytes (stop if QTc over 500 ms).

Monitoring. Conviction, preoccupation and distress, risk, adherence, adverse effects, weight and metabolic indices (baseline, 6 weeks, 3 months, then annually), prolactin, ECG, and substance use. Review within 1 to 2 weeks after starting treatment, then monthly until stable.

Referral and escalation. Psychiatry the same day for risk of violence or suicide, psychotic depression, mania, postpartum onset, food refusal, or delusions involving children. Early intervention in psychosis services for young people with first episodes. Neurology for encephalitis, epilepsy, dementia and movement disorders. Old age psychiatry. Dermatology and psychiatry joint care for delusional infestation.

Forensic services and police liaison when there is risk to others. Addiction services. Admission criteria. Imminent risk of harm to self or others, delusions with action on them, inability to eat or drink or care for self, severe agitation, catatonia, psychotic depression with suicidal intent, delirium requiring inpatient care, and failure of community treatment. Use mental health legislation when criteria are met.

Discharge and follow up. Written crisis plan, medication education, early review in 1 to 2 weeks, family and carer involvement, and relapse signature. Safety net advice: return or call urgently for thoughts of harming self or others, refusal of food or medicines, new confusion, fever, stiffness, tremor or rigid muscles after starting an antipsychotic, sore throat or fever on clozapine, or stopping medicines.