What medications are used to treat paranoia?

Medications for Paranoia

Atypical antipsychotics are the first-line treatment for paranoia, with risperidone (0.5-3.5 mg/day) as the preferred agent, followed by olanzapine (2.5-15 mg/day) and quetiapine (25-300 mg/day) as high-quality alternatives. 1, 2

Primary Treatment Recommendations

First-Line Agents

• Risperidone is the preferred atypical antipsychotic for paranoid symptoms across multiple conditions including late-life schizophrenia (1.25-3.5 mg/day), delusional disorder, and agitated dementia with delusions (0.5-2.0 mg/day) 1, 2
• Olanzapine (2.5-15 mg/day depending on condition) is a high second-line option, particularly effective for agitation and combativeness, with FDA approval for acute agitation in schizophrenia and bipolar disorder 1, 3, 2
• Quetiapine (25-300 mg/day) is another high second-line choice, especially valuable in patients with Parkinson's disease where it does not worsen motor function 1, 2, 4

Second-Line Agents

• Aripiprazole (5-30 mg/day) is a viable alternative with lower risk of extrapyramidal symptoms, though it ranks below risperidone and olanzapine in expert consensus 1, 2
• Clozapine is highly effective but reserved for treatment-resistant cases due to agranulocytosis risk requiring mandatory blood monitoring 5, 4, 6

Agents to Avoid

• Haloperidol and other typical antipsychotics should be avoided as first-line treatment due to high risk of extrapyramidal symptoms and potential for irreversible tardive dyskinesia (50% risk in elderly after 2 years of continuous use) 1, 7
• Typical antipsychotics are associated with significant adverse effects involving cholinergic, cardiovascular, and extrapyramidal systems without demonstrable superiority over atypical agents 1, 6

Special Population Considerations

Elderly Patients

• Start with lower doses: risperidone 0.25-0.5 mg/day, olanzapine 2.5-5 mg/day, quetiapine 12.5-25 mg/day 1, 2
• Elderly patients are at particularly high risk for adverse effects and require careful dose titration 7

Patients with Parkinson's Disease

• Quetiapine is first-line (does not worsen motor function) 2, 4
• Clozapine is effective but requires blood monitoring 4
• Avoid risperidone and olanzapine as they may deteriorate motor function 4

Patients with Metabolic Concerns

• Avoid clozapine and olanzapine in patients with diabetes, dyslipidemia, or obesity 2
• Prefer risperidone or quetiapine in these populations 2

Patients with Cardiac Issues

• Avoid clozapine, ziprasidone, and low-potency conventional antipsychotics in patients with QTc prolongation or congestive heart failure 2

Duration of Treatment

Treatment duration varies by underlying condition 1:

• Delirium: 1 week after symptom resolution
• Agitated dementia: Taper within 3-6 months to determine lowest effective maintenance dose
• Schizophrenia/Delusional disorder: Indefinite treatment at lowest effective dose
• Psychotic depression: 6 months after remission
• Psychotic mania: 3 months after stabilization

Critical Pitfalls to Avoid

• Never combine two antipsychotics (e.g., olanzapine plus haloperidol) as this increases adverse effects without clear additional benefit 7
• Avoid benzodiazepines as first-line treatment for paranoia; they are deliriogenic and increase fall risk, though they may have a role in crisis management of severe agitation 1
• Do not use antipsychotics for non-psychotic conditions such as panic disorder, generalized anxiety disorder, or non-psychotic depression 2
• Monitor for excessive sedation when combining antipsychotics with other CNS-active medications 7

Monitoring Requirements

• Assess for extrapyramidal symptoms regularly, particularly with higher doses 1, 7
• Monitor metabolic parameters (weight, glucose, lipids) with olanzapine and clozapine 3, 2
• Check for orthostatic hypotension during initial titration, especially with quetiapine 1, 2
• Mandatory weekly blood counts for first 6 months with clozapine due to agranulocytosis risk 5