First-Line Antipsychotic in First Episode Psychosis
Atypical antipsychotics, specifically risperidone 2 mg/day or olanzapine 7.5-10 mg/day, should be used as first-line treatment for first-episode psychosis, with these low doses being both effective and better tolerated than higher doses or typical antipsychotics. 1
Recommended Initial Dosing
Start with low doses and titrate slowly:
- Risperidone: Begin at 2 mg/day as the initial target dose 1
- Olanzapine: Begin at 7.5-10 mg/day as the initial target dose 1
- Maximum doses should generally not exceed 4 mg/day risperidone or 20 mg/day olanzapine in first-episode patients 1
The rationale for these low doses is critical: extrapyramidal side-effects must be avoided to encourage future medication adherence, which directly impacts long-term morbidity and quality of life 1.
Dosing Algorithm
Initial titration approach:
- Start risperidone at 1 mg/day, increase to 2 mg after 3 days 2
- Assess response frequently, but increase doses only at widely spaced intervals (14-21 days after initial titration) if response is inadequate 1
- Titrate only within the limits of sedation and emergence of extrapyramidal side-effects 1
- Most first-episode patients require only 1-4 mg/day risperidone; only 3% require doses over 6 mg/day 2
Why Atypical Over Typical Antipsychotics
Although typical antipsychotics may be as efficacious as atypical antipsychotics in reducing positive psychotic symptoms, they are less well tolerated even at low doses 1. This tolerability difference is crucial because:
- First-episode patients have high rates of extrapyramidal symptoms when treated with typical antipsychotics 3
- The severity of extrapyramidal symptoms is significantly lower with risperidone compared to haloperidol 4
- Significantly fewer patients require antiparkinsonian medication with atypical agents 4
- Better tolerability translates to improved long-term adherence and outcomes 1, 5
Evidence for Low-Dose Efficacy
Low doses are highly effective in first-episode psychosis:
- At 2-4 mg/day risperidone, 62-80% of first-episode patients achieve clinical response 3
- 63% of risperidone-treated first-episode patients show clinical improvement (≥50% reduction in symptom scales) 4
- There is no significant difference in efficacy between 1-4 mg/day and 5-8 mg/day dose groups 2
- Low doses (≤6 mg/day) have significantly lower extrapyramidal symptoms compared to high doses (>6 mg/day) 4
Critical Pitfalls to Avoid
Do not use typical antipsychotics as first-line:
- While haloperidol may be used, the maximum should be 4-6 mg/day in first-episode psychosis 1
- Even at these low doses, typical agents cause more extrapyramidal side-effects than atypicals 1
Do not escalate doses too quickly:
- Behavioral symptoms respond first, followed by affective symptoms, then cognitive and perceptual symptoms 6
- Premature dose escalation increases side effects without improving efficacy 2, 4
Do not assume higher doses are needed:
- First-episode patients are more sensitive to antipsychotics than chronic patients 4, 5
- The mean daily dose required by first-episode patients is approximately 4 mg risperidone 5
Treatment Duration Considerations
If positive psychotic symptoms persist after a trial of two first-line atypical antipsychotics (around 12 weeks), review reasons for treatment failure 1. This includes assessing: