What is the recommended medication regimen for treating psychosis?

Medication for Psychosis

For first-episode psychosis, start with risperidone 2 mg/day or olanzapine 7.5-10 mg/day as first-line treatment, using atypical antipsychotics due to superior tolerability and lower risk of extrapyramidal symptoms compared to typical agents. 1, 2

Initial Medication Selection

• Atypical antipsychotics are the preferred first-line agents over typical antipsychotics, even though efficacy for positive symptoms may be similar, because they cause significantly fewer extrapyramidal side effects and better long-term adherence 1, 2

• Risperidone 2 mg/day is the recommended starting dose for first-episode psychosis, with a maximum of 4 mg/day in this population 1, 2

• Olanzapine 7.5-10 mg/day is an alternative first-line option, with a maximum dose of 20 mg/day 1, 2

• Typical antipsychotics like haloperidol should be avoided as first-line treatment, but if used, must not exceed 4-6 mg/day due to high risk of extrapyramidal symptoms 1, 2

Dosing Algorithm and Titration

• Start low and go slow: Begin at the recommended initial doses and only increase if response is inadequate after adequate trial periods 1, 2

• Wait 14-21 days after initial titration before increasing doses to minimize extrapyramidal side effects and allow time for therapeutic response 1, 2

• Dose increases should be made in small increments (25-50 mg for risperidone) and only within the limits of sedation and emergence of extrapyramidal symptoms 1, 2

• Clinical trials demonstrate that even 2 mg/day risperidone is highly effective in first-episode patients, with 62-85% response rates at low doses 3, 4

Treatment Response Timeline

• Allow 4-6 weeks for an adequate trial before concluding treatment failure and switching medications 2

• If positive psychotic symptoms persist after approximately 12 weeks on two different first-line atypical antipsychotics, review potential reasons for treatment failure 1

• Before switching medications, systematically evaluate: medication adherence, concurrent substance use, underlying medical conditions causing secondary psychosis, and psychosocial stressors 1, 2

Special Populations

• Elderly patients require lower starting doses: Begin risperidone at 50 mg/day with 50 mg/day increments, or start at the lower end of dosing ranges and titrate slowly 2, 5

• Hepatically impaired patients: Start risperidone at 25 mg/day with 25-50 mg/day increments to effective dose 5

• Adolescents (13-17 years) with schizophrenia: Start risperidone at 25 mg twice daily, increasing to 400-800 mg/day range over several days 5, 6

Monitoring Requirements

• Monitor for extrapyramidal symptoms at every visit, as avoiding these side effects is critical for future medication adherence 2

• Assess for sedation, which is a common dose-limiting side effect reported in 23% of patients 4

• For atypical antipsychotics, mandatory baseline and ongoing monitoring includes: BMI, waist circumference, blood pressure, HbA1c or fasting glucose, lipid panel, and ECG 7

• Maintain continuity of care with the same treating clinicians for at least the first 18 months of treatment 2

Treatment-Resistant Psychosis

• For treatment-resistant cases after adequate trials of two atypical antipsychotics, consider clozapine, though it requires close monitoring for agranulocytosis 2

• Clozapine should be reserved for truly refractory cases due to its significant anticholinergic properties and potential for cognitive worsening, particularly in elderly patients 8

Critical Pitfalls to Avoid

• Never use excessive doses in first-episode psychosis (>4 mg/day risperidone, >20 mg/day olanzapine), as higher doses increase side effects without improving efficacy 1, 2

• Do not switch medications too quickly before completing a 4-6 week adequate trial period 2

• Always rule out secondary causes of psychosis before initiating psychiatric treatment, including neurologic conditions, substance use, and medical illnesses 2, 8

• Avoid neglecting psychosocial interventions and family involvement, which are essential components of comprehensive treatment 2

• Do not fail to develop supportive crisis plans to facilitate recovery and treatment acceptance 2

Drug Interactions

• Reduce risperidone dose to one-sixth when co-administered with potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 5

• Increase dose up to 5-fold when used with chronic CYP3A4 inducers (phenytoin, carbamazepine, rifampin) for >7-14 days 5

Context-Specific Considerations

• For bipolar disorder with psychosis: Atypical antipsychotics can be used as monotherapy or adjunctively with lithium or valproate at doses of 400-800 mg/day 7, 6

• For psychosis in Parkinson's disease: Quetiapine or clozapine are preferred due to minimal effects on motor function; first taper other anti-parkinsonian medications if possible 8

• For psychosis in Alzheimer's disease: Risperidone 0.5-3 mg/day is first-line, followed by low-dose haloperidol or olanzapine if unsuccessful 8