What treatment approach is recommended for a 65-year-old female patient with a 16-year history of delusions of persecution, hypertension (HTN), and diabetes mellitus (DM), who is not currently taking any psychotropic medications?

Treatment Approach for Chronic Delusional Disorder with Medical Comorbidities

Start risperidone at 1-2 mg daily as first-line treatment for this patient's 16-year history of persecutory delusions, with careful monitoring of her hypertension and diabetes. 1, 2, 3

Rationale for Antipsychotic Selection

Risperidone as First-Line Agent

• Risperidone demonstrates the highest treatment response rates for delusional disorders, with 57% response rates in recent comparative studies of antipsychotics for delusional conditions 2
• The drug has established efficacy specifically for persecutory-type delusional disorder, with documented resolution of symptoms in controlled trials 1
• Lower doses (1-2 mg daily) are effective for first-episode or treatment-naive psychotic patients, minimizing extrapyramidal side effects 4, 5
• Risperidone is considered safer than older agents like pimozide and should be first-line therapy for monosymptomatic delusional disorders 3

Alternative: Amisulpride

• Amisulpride showed the highest mean treatment response (67%) in head-to-head comparisons, though risperidone remains more widely available and studied 2
• Consider amisulpride if risperidone fails or causes intolerable side effects 2

Dosing Strategy

Initial Titration

• Start risperidone at 1 mg daily, increasing to 2 mg daily after one week 4, 1
• This low-dose approach (significantly lower than the 4-6 mg used for chronic schizophrenia) reduces extrapyramidal side effects while maintaining efficacy 4, 5
• Avoid rapid dose escalation; assess response at 14-21 day intervals before increasing 4

Target Dose Range

• Maintain at 2 mg daily for most patients with delusional disorder 4
• Maximum 4 mg daily if inadequate response after 6-8 weeks 5
• The goal is the lowest effective dose to minimize metabolic and cardiovascular risks given her HTN and DM 4

Critical Monitoring for Medical Comorbidities

Diabetes Management

• Monitor fasting glucose and HbA1c at baseline, 1 month, 3 months, then quarterly 4
• Risperidone has lower metabolic risk than olanzapine or quetiapine, making it preferable in diabetic patients 4
• Watch for weight gain, which occurs less frequently at low doses 5

Hypertension Considerations

• Monitor blood pressure at each visit, as antipsychotics can affect cardiovascular parameters 4
• Avoid chlorpromazine due to hypotensive effects 4
• Risperidone at low doses has minimal cardiovascular effects compared to first-generation antipsychotics 5

Treatment Duration and Reassessment

Initial Trial Period

• Continue treatment for 12 weeks minimum to assess full response 4
• If positive response occurs, continue for 6 months to 2 years 4
• After sustained remission (6-24 months), consider gradual dose reduction with patient consent 4

If Treatment Fails

• Switch to amisulpride or aripiprazole after 12 weeks of inadequate response 6, 2
• Aripiprazole (10-15 mg daily) may be particularly useful given its favorable metabolic profile and efficacy in delusional disorder 6
• Avoid antipsychotic polypharmacy—switch rather than add agents to minimize side effects and drug interactions 4

What NOT to Do

Avoid These Approaches

• Do not use haloperidol or first-generation antipsychotics—they offer no benefit over atypicals and cause more extrapyramidal side effects 4
• Do not use benzodiazepines as primary treatment for delusions; they are deliriogenic and worsen cognition 4
• Do not use olanzapine or quetiapine as first-line in diabetic patients due to higher metabolic risks 4, 2
• Do not prescribe anticholinergics prophylactically—they impair cognition and worsen psychosis 5

Practical Considerations

Adherence Strategies

• Single daily dosing improves adherence 4
• Consider long-acting injectable risperidone if oral adherence becomes problematic 4
• Address the 16-year duration without treatment by explaining the rationale clearly and setting realistic expectations 4

Monitoring Extrapyramidal Side Effects

• Assess for abnormal movements at baseline, as untreated psychotic patients may have pre-existing movement disorders 5
• Less than 10% of patients on low-dose risperidone require anticholinergic medication 5
• If extrapyramidal symptoms emerge, reduce dose or switch to aripiprazole rather than adding anticholinergics 6