Low-dose versus standard-dose antipsychotic treatment in first-episode schizophrenia: A secondary analysis of EUFEST data.

In 30 seconds

This secondary analysis of the open-label randomized EUFEST trial compared outcomes by dose group among 421 participants with first-episode schizophrenia. Participants were classified as receiving low-dose or standard-dose antipsychotics using guideline-based thresholds; dose itself was not randomized. Study discontinuation patterns were similar (adjusted hazard ratio for standard-dose versus low-dose treatment, 0.86 [95% CI 0.56-1.32]), as were PANSS symptom trajectories. The low-dose group had significantly less longitudinal weight gain after adjustment, but also differed at baseline, including having lower symptom severity and higher functioning.

Key findings

• Of 421 participants, 58 (13.8%) received low doses and 363 (86.2%) standard doses.
• Discontinuation patterns were similar; the adjusted hazard ratio for standard-dose versus low-dose treatment was 0.86 (95% CI 0.56-1.32).
• PANSS total-score trajectories did not differ between dose groups over time.
• The low-dose group had significantly less longitudinal weight gain after adjustment for baseline characteristics and antipsychotic drug.

Why it matters

The findings suggest that lower-end recommended doses may be feasible for some people starting treatment for first-episode schizophrenia, with no observed disadvantage in treatment continuation or symptom trajectories and potentially less weight gain. Weight gain is a relevant treatment outcome, but the dose-group comparison and baseline differences mean these results should be interpreted as suggestive rather than definitive.

What to keep in mind

Dose strategy was not randomized: this was a secondary analysis that classified participants by received dose, and the groups differed in baseline characteristics. The authors state that randomized dose-strategy trials are needed for confirmation.