Initial lurasidone dosing in acute schizophrenia: Pragmatic and trajectory-aware clinical implications

Abstract

Selecting the initial antipsychotic dose is a high-impact decision in acute schizophrenia. A randomized study found that starting lurasidone at 80 mg/day for 1 week (then flexible titration) produced earlier reductions in Positive and Negative Syndrome Scale positive symptoms than 40 mg/day, without higher discontinuations for adverse events or a metabolic penalty over 6 weeks. These data support an individualized approach: Start at 80 mg/day when rapid control of positive symptoms or agitation is needed and tolerance permits; start at 40 mg/day when akathisia risk or patient preference argues for caution, with a planned day-7 review for up-titration. The open-label design, dose convergence after week 1, and the lack of stratified randomization limit attribution of longer-term advantages to starting dose. Even so, the trial reframes initial dose as a modifiable lever for the early course rather than a one-size-fits-all rule and warrants confirmation in larger, double-blind randomized trials.

Keywords: Lurasidone; Schizophrenia; Antipsychotic agents; Treatment outcome; Akathisia; Body weight

Core Tip: Choosing a starting dose may influence the early clinical trajectory in acute schizophrenia. In a pragmatic randomized study, 80 mg/day for the first week led to more rapid improvement in Positive and Negative Syndrome Scale positive symptoms than 40 mg/day, with similar discontinuation for adverse events and no short-term metabolic penalty. Clinicians may prioritize speed with 80 mg/day when tolerated, or start at 40 mg/day when akathisia risk is a concern, coupled with a day-7 review for escalation. Open-label design and dose convergence temper causal claims, but initial dose selection may shape the early trajectory.