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Pharmacokinetic correlates of clinical response in a retrospective naturalistic cohort of patients treated with long-acting injectable antipsychotics

Year: 2025

Type: article

Abstract: OBJECTIVE: To investigate the pharmacokinetic correlates of clinical response to long acting injectable (LAI) antipsychotics in a naturalistic outpatient sample. METHODS: We conducted a retrospective cohort study of LAI-treated outpatients. Steady-state trough antipsychotic plasma concentrations were classified as subtherapeutic, within, or supratherapeutic based on established therapeutic reference ranges (TRRs). Clinical response was defined as Clinical Global Impression Improvement score ≤ 2. Generalized linear mixed models were used to analyze predictors of treatment response. RESULTS: In a total of 158 LAI-treated outpatients, responders (42.4 %) were significantly younger (50.5 vs. 55.6 years, p = 0.002) and more often treated with monotherapy (64.2 % vs. 44.0 %, p = 0.01). Half of the responders (51.1 %) had antipsychotic levels below the TRR (51.1 %), and 42.2 % had levels within TRR, while there were no responders with supratherapeutic concentrations (p = 0.01). After controlling for age, sex, body mass index, smoking, LAI monotherapy, and symptom severity, patients with subtherapeutic plasma concentrations (adjusted odds ratio (aOR): 31.97, 95 % confidence interval (CI): 1.74-588.55, p = 0.02) and with levels within the TRR (aOR: 23.01, 95 % CI: 1.28-414.48, p = 0.03) had higher probability of treatment response compared to those with supratherapeutic concentrations, while these estimates were limited by the small group size (n = 9). Younger age (aOR: 0.97, 95 % CI: 0.94-0.99, p = 0.04) and LAI monotherapy (aOR = 3.77, 95 % CI = 2.19-6.51, p = 0.001) were associated with better treatment response. CONCLUSIONS: Assessing antipsychotic concentrations combined with clinical characteristics such as LAI monotherapy and age may be useful for guiding pharmacotherapy with LAIs.

Source: Schizophrenia Research

DOI: 10.1016/j.schres.2025.12.012