What is the treatment for delusions of persecution?

Treatment of Persecutory Delusions

The initial treatment for persecutory delusions should be atypical antipsychotics, with olanzapine, quetiapine, or aripiprazole being the preferred first-line pharmacological options, supplemented by nonpharmacological interventions. 1

Pharmacological Management

First-line Treatment Options

• Atypical (second-generation) antipsychotics are preferred over first-generation antipsychotics due to their more favorable side effect profile 1
• Recommended atypical antipsychotics include:
  • Olanzapine (starting dose 2.5-5 mg orally daily) - may cause drowsiness and orthostatic hypotension 1
  • Quetiapine (starting dose 25 mg immediate release orally) - has sedating properties which may be beneficial in agitated patients 1
  • Aripiprazole - may offer benefit with fewer metabolic side effects 1

Second-line Treatment Options

• First-generation antipsychotics should be considered when atypical antipsychotics are ineffective or contraindicated:
  • Haloperidol (0.5-1 mg orally or subcutaneously) - caution regarding extrapyramidal side effects 1
  • Methotrimeprazine (5-12.5 mg orally or subcutaneously) - has sedating and anticholinergic effects 1

Important Considerations

• Use the lowest effective dose for the shortest possible duration to minimize side effects 1
• Lower starting doses should be used in older or frail patients (e.g., 0.25-0.5 mg for haloperidol) 1
• Benzodiazepines should not be used as first-line treatment for agitation associated with delusions 1
• Combination pharmacotherapy can be considered after two different trials with two different classes of agents at sufficient doses 1

Nonpharmacological Interventions

First-line Nonpharmacological Approaches

• Nonpharmacological interventions should be initiated when there are no immediate safety concerns 1
• Cognitive therapy focused on identifying and challenging irrational beliefs related to persecution 1
• Emotional Processing and Metacognitive Awareness (EPMA) interventions to reduce distress associated with persecutory delusions 2
• Exposure therapy to help patients confront trauma-related situations that may be contributing to paranoia 1

Environmental and Behavioral Interventions

• Environmental modifications to reduce triggers that may exacerbate delusions 1
• Social contact interventions to improve interpersonal relationships 1
• Address safety behaviors that maintain delusions (actions carried out to reduce perceived threat) 3
• Sensory and activities therapy tailored to individual needs 1

Assessment and Monitoring

Initial Evaluation

• Medical evaluation to identify and manage underlying contributors to delusions 1
• Assessment for adverse medication effects, infections, dehydration, pain, or other medical conditions that could exacerbate symptoms 1
• Screening for safety risks, including threats or attempts to harm self or others 1

Ongoing Monitoring

• Evaluate response to treatment within 30 days; refer to mental health professional if minimal or no improvement 1
• For pharmacological treatments used for delusions, attempt tapering or discontinuation after 6 months of symptom stabilization 1
• Monitor for side effects of antipsychotic medications, particularly extrapyramidal symptoms and metabolic effects 1

Special Populations

Older Adults

• Persecutory delusions are common in dementia (26.9% prevalence) and require careful management 4
• Patients with dementia and persecutory delusions often have higher rates of physically aggressive behaviors 4
• In older adults, use lower doses of antipsychotics and titrate gradually 1
• Avoid antipsychotics in patients with Parkinson's disease or dementia with Lewy bodies due to risk of extrapyramidal side effects 1

Patients with Genetic Risk Factors

• Consider genetic testing in patients with family history of frontotemporal dementia or other neurodegenerative diseases 1
• Persecutory delusions may be an early symptom in patients with C9orf72 repeat expansions 1

Pitfalls and Caveats

• Avoid using benzodiazepines as first-line treatment for agitation in delirious patients 1
• Do not use cholinesterase inhibitors to prevent or treat delirium with psychotic features 1
• Antipsychotics should not be used in patients with mild-to-moderate delirium as they may worsen symptoms 1
• Always assess for underlying medical causes before attributing persecutory delusions solely to psychiatric illness 1
• Recognize that persecutory delusions exist on a spectrum and may be part of various conditions including schizophrenia, dementia, delirium, or other medical conditions 5