Plasmatic Levels and Response to Variable Doses of Monthly Aripiprazole and Three-Month Paliperidone in Patients with Severe Schizophrenia. Treatment Adherence, Effectiveness, Tolerability, and Safety

Juan J Fernández-Miranda,1,2,* Silvia Díaz-Fernández1,2,* 1AGC de Salud Mental V, Hospital Universitario de Cabueñes, Servicio de Salud del Principado de Asturias (SESPA), Gijón, Spain; 2Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain*These authors contributed equally to this workCorrespondence: Juan J Fernández-Miranda, AGC de Salud Mental V, Hospital Universitario de Cabueñes, Servicio de Salud del Principado de Asturias (SESPA), C/ Centro Especialidades Avelino González. Óran s/n, Gijón, Asturias, 33211, Spain, Email juanjose.fernandezmi@sespa.es; juanjofmiranda@gmail.comIntroduction: There is a need when optimizing antipsychotic treatment to know the plasmatic levels (PLs) achieved with the different doses and their relationship with effectiveness and toxicity, especially in patients with poor clinical progress. This study investigates the dose-PL-response relationship of monthly aripiprazole (AOM) and three-month paliperidone (PP3M).Methods: Observational, 52-week prospective study of patients with severe schizophrenia (CGI-S ≥ 5) treated with PP3M or AOM for at least one year before their inclusion in the study (N=68). Dose-PL relationship was determined. Subjects were included in standard-dose and high-dose (above labeled) and standard/therapeutic range-PLs and high-PLs (above range) groups. Treatment adherence, effectiveness (hospitalizations, severity), tolerability and safety were assessed. PLs and clinical response were evaluated.Results: No clear linear relationship was found between doses and PLs. In a considerable number of cases, standard doses achieved PLs above the therapeutic range. A significant clinical improvement was related to high PLs, without less safety, tolerability, or treatment compliance being involved. Clinical severity decreased more frequently in patients who received high doses and reached high PLs. Hospital admissions decreased significantly in those patients with high PLs.Conclusion: Taking into account the absence of a linear relationship between doses and PLs, the effectiveness in people with severe schizophrenia of AOM and PP3M depends on reaching high PLs, achieved with high doses, but also with standard doses in some cases, without leading to worse treatment tolerability, safety, or adherence.Keywords: schizophrenia, long-acting injectable antipsychotic, dose, plasmatic levels, effectiveness, tolerability