Comparative efficacy of quetiapine by dose and formulation for psychosis in schizophrenia: A systematic review and dose-response model-based network meta-analysis

Background: Quetiapine has varied dose ranges and immediate-(QTP-IR) and extended-release (QTP-ER) formulations. Aims: We hypothesized that QTP-IR is inferior to QTP-ER at any dose in efficacy for the acute treatment in schizophrenia and tested using a dose-response model-based network meta-analysis (NMA). Methods: We searched PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov for randomized placebo-controlled trials comparing QTP-IR and/or QTP-ER for acute psychosis in patients with schizophrenia up to September 21, 2022. A random effect Bayesian dose-response model-based NMA was performed to compare the dose-response relationships between QTP-IR and QTP-ER. Results: The relationship between doses and antipsychotic effects was partially bell-shaped for QTP-IR but not for QTP-ER. The respective peak effect dose was 279.7 mg for QTP-IR and 557.2 mg for QTP-ER, with no significant difference in peak effect. QTP-IR ranging from 100 to 300 mg were significantly superior to QTP-ER at the same doses. In addition, QTP-IR ranging from 100 to 400mg were significantly better than placebo, whereas QTP-ER ranging from 500 to 800 mg were significantly more effective than placebo. Moreover, QTP-IR 600 mg was significantly less effective than QTP-ER at the same dose. Furthermore, QTP-IR 700 mg was significantly superior to placebo, but significantly inferior to QTP-ER 600 mg. Conclusions: QTP-IR may reach comparable peak responses and exhibit enhanced antipsychotic effects at lower doses than QTP-ER; the converse may be true at relatively high doses. Collectively, we propose a novel strategy to enhance the efficacy of QTP administration.

Automated summary

This study used a dose-response model-based network meta-analysis to compare the efficacy of immediate-release (QTP-IR) and extended-release (QTP-ER) formulations of quetiapine for the acute treatment of schizophrenia. The results showed that QTP-IR may exhibit comparable peak responses and enhanced antipsychotic effects at lower doses compared to QTP-ER, but may be less effective at higher doses.