Disease-specific therapeutic plasma concentration ranges for quetiapine in schizophrenia, manic episode, depressive episode, and depressive comorbid insomnia.

objectiveTo establish disease-specific therapeutic plasma concentration ranges for quetiapine (QTP) and its active metabolite N-desalkylquetiapine (NDQ) in Chinese patients with schizophrenia, manic episode, depressive episode, and depressive episode with comorbid insomnia, and to evaluate the impact of polypharmacy on drug concentrations.

methodsA Retrospective Analysis was conducted from June 2022 to October 2025, enrolling 576 hospitalized patients: 198 with schizophrenia, 186 with manic episode, and 192 with a depressive episode. From the depressive episode group, 35 patients with severe comorbid insomnia as the primary treatment target were analyzed separately. Consequently, the core depressive episode group for efficacy analysis comprised 157 patients, while the depressive episode with comorbid insomnia subgroup (n = 35) was analyzed separately. Detailed administration regimens (dosage frequency) were recorded for all patients. Steady-state concentrations of QTP and NDQ were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

resultsSignificant differences in optimal QTP concentration ranges were identified across diseases: 150-550 ng/mL for schizophrenia, 180-580 ng/mL for manic episode, 120-480 ng/mL for depressive episode (consistent with both ≥ 30% and ≥ 50% HAMD-17 reduction standards), and 40-120 ng/mL for depressive episode with comorbid insomnia (12 h concentrations). The mean QTP concentration was lower in the depressive episode group (302 ± 276 ng/mL), which showed a high response rate (82.3% for ≥ 30% HAMD-17 reduction). The highest response rate (85.7%) was observed in the depressive episode with comorbid insomnia subgroup. In contrast, schizophrenia patients required higher concentrations (389 ± 286 ng/mL) but had a lower response rate (73.7%). Polypharmacy with CYP3A4 inhibitors/inducers was recorded; co-administration of venlafaxine (mild CYP3A4 inhibitor) significantly increased QTP concentrations in depressive episode patients, while co-administration of valproate or lithium had no significant impact on QTP concentrations in schizophrenia or manic episode patients.

conclusionThis exploratory study proposes disease-specific QTP concentration ranges that show clinical relevance in this Chinese cohort, providing preliminary evidence to guide future research on personalized TDM. The findings should be interpreted cautiously and require validation in subsequent studies before being used to inform clinical practice.