What is the recommended treatment for an adult with paranoid psychosis without contraindications?

Treatment of Paranochia (Paranoid Psychosis)

First-Line Treatment: Atypical Antipsychotics

For an adult with paranoid psychosis without contraindications, start with an atypical antipsychotic—specifically risperidone 0.5-1 mg daily, titrating to a target dose of 2 mg/day, or olanzapine 2.5-5 mg daily, titrating to 7.5-15 mg/day. 1, 2

Rationale for Atypical Antipsychotics as First-Line

• Atypical antipsychotics are now considered first-line treatment for all psychotic disorders, including paranoid presentations, due to their superior tolerability profile compared to typical antipsychotics like haloperidol. 3, 4

• The 2025 INTEGRATE international guidelines emphasize shared decision-making and individualized treatment based on side-effect profiles, with atypical antipsychotics offering significantly fewer extrapyramidal symptoms (EPS) and lower risk of tardive dyskinesia. 1

• Typical antipsychotics like haloperidol should be avoided as first-line unless atypical agents are unavailable or cost-prohibitive, as they carry higher risks of movement disorders that severely impact future medication adherence. 2

Specific Medication Recommendations

Risperidone (Preferred Option)

• Start at 0.5-1 mg daily, with target maintenance dose of 2 mg/day for most patients. 2
• Do not exceed 6 mg/day, as extrapyramidal symptoms increase significantly at doses ≥2 mg/day. 2
• Risperidone offers comparable efficacy to haloperidol with significantly fewer extrapyramidal side effects. 2

Olanzapine (Alternative First-Line)

• Start at 2.5-5 mg daily, titrating to 7.5-15 mg/day as needed. 5
• Olanzapine has the safest cardiac profile among antipsychotics, with only 2 ms mean QTc prolongation. 2
• This agent has a diminished risk of developing extrapyramidal symptoms and tardive dyskinesia compared to haloperidol. 2

Other Atypical Options

• Quetiapine 100-300 mg/day is a high second-line option, though more sedating with risk of transient orthostasis. 2, 5
• Aripiprazole 15-30 mg/day is also a high second-line option for late-life schizophrenia. 5

Treatment Timeline and Monitoring

Acute Phase (First 4-6 Weeks)

• Give the first antipsychotic at therapeutic dose for at least 4 weeks before assessing efficacy. 1
• Immediate effects are more likely due to sedation; antipsychotic effects become apparent after the first week or two. 1
• If significant positive symptoms persist after 4 weeks, discuss switching to an alternative antipsychotic based on side-effect profiles. 1

Recuperative Phase (4-12 Weeks)

• As positive symptoms improve, maintain antipsychotic medication as additional improvement may occur over 6-12 months following acute presentation. 1
• Consider gradually lowering dosage to decrease side effects, but monitor carefully to avoid relapse. 1

Maintenance Phase

• Most patients with psychotic disorders need long-term antipsychotic medication therapy, as approximately 65% receiving placebo will relapse within 1 year compared to 30% receiving antipsychotics. 1
• For newly diagnosed patients symptom-free for at least 6-12 months, a medication-free trial may be considered, but any evidence of disorder warrants ongoing treatment. 1

Critical Monitoring Parameters

• Monitor for extrapyramidal symptoms at every visit, as these predict poor long-term adherence. 2
• Obtain baseline ECG if cardiac risk factors are present, as both typical and atypical antipsychotics can prolong QTc interval. 2
• Assess treatment effectiveness early and use a proactive approach when switching or augmenting treatment due to inadequate efficacy or poor tolerability. 1

Treatment-Resistant Cases

• If patient fails two or more adequate trials of different antipsychotic agents (including at least one atypical), consider clozapine. 1
• Clozapine is the only antipsychotic with documented superiority in efficacy for treatment-resistant cases, though it carries significant side effect risks. 1, 3
• A medication-free trial may be indicated for some treatment-resistant cases to reassess diagnosis, though this often requires inpatient setting. 1

Common Pitfalls to Avoid

• Do not use haloperidol as first-line unless atypical antipsychotics are unavailable, as it carries higher risk of movement disorders even at low doses. 2
• Avoid instituting large dosages during early treatment, as this does not hasten recovery and more often results in unnecessarily excessive doses and side effects. 1
• Do not use benzodiazepines alone to treat psychosis, as they do not address psychotic symptoms; they may be used adjunctively for acute agitation. 2, 6
• Avoid thioridazine entirely due to severe QTc prolongation (25-30 ms). 2

Special Populations

Elderly Patients

• Start at lower doses: risperidone 0.25 mg daily or olanzapine 2.5 mg daily, as patients over 50 years experience more profound sedation. 2, 7
• Maximum risperidone dose 2-3 mg/day in divided doses for elderly patients. 2

Patients with Cardiac Disease

• Olanzapine is the safest option with minimal QTc prolongation. 2
• Avoid haloperidol (7 ms QTc prolongation) and thioridazine (25-30 ms QTc prolongation). 2