Plasma Levels of Long-Acting Injectable Antipsychotics in Outpatient Care: A Retrospective Analysis

Abstract

Purpose Antipsychotic efficacy in schizophrenia depends on its availability in the body. Although therapeutic outcomes remain still far from satisfactory, therapeutic drug monitoring is not a common part of clinical practice during treatment with long-acting injectable antipsychotics (LAI AP). The real effectiveness of LAI AP is thus uncertain. Patients and Methods We made a retrospective evaluation of plasma levels of LAI AP. Collection of blood samples was performed just before the drug application and one week later. Forty patients with a stabilized clinical condition and steady-state plasma levels were included. Results In the observed cohort of patients, flupentixol decanoate (n = 23) was the most often used drug, followed by fluphenazine decanoate (n = 7), haloperidol decanoate (n = 5), paliperidone palmitate (n = 3), and risperidone microspheres (n = 2). Just 5 of 40 patients were treated with a monotherapy. In the period before the application, 60% of the patients did not reach the therapeutic reference range (TRR) and 20% of the patients had an undetectable plasma level. At the time of collection of the second blood samples performed after 7 days, 24% of the patients were under the TRR. Conclusion We have found a surprisingly high incidence of plasma levels under the TRR in patients treated with LAI AP. Notwithstanding individual variability in pharmacokinetics, it seems that LAI AP may be underdosed in usual clinical practice.

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

“… 17 , 19 , 35 , 39 , 55 In short, knowing the relationship between dose and PLs, and between PLs and effectiveness and tolerability, would enable optimization of treatment. 41 , 43 , 45 …”

“…Therapeutic monitoring could help to overcome this uncertainty. 27 , 45 , 57 , 58 It has to be noted that the vast majority of patients have been previously treated with other antipsychotics without acceptable results, and a considerable number would be candidates for clozapine because they are “resistant”. 49 , 50 (In fact, some of them combine clozapine with AOM or PP3M).…”

“… 43 , 44 However, there are still doubts regarding its usefulness in clinical practice, given the interindividual variability in the pharmacokinetics of APs and the dose-PL and dose-response (effectiveness and toxicity) relationships. 40 , 41 , 44 , 45 …”

Therapeutic Drug Monitoring of Long-Acting Injectable Antipsychotics as a Predictor of Relapse in Schizophrenia Spectrum Disorders: A 1-Year Pilot Study

“…The finding of lower-than-expected LAI serum levels proved to be remarkably common and in-line with previous realworld data on psychotropic drugs, 42 including LAIs. 21,23,43 More specifically, O-LAI proved to be most commonly associated with underrange values, which may be explained by various factors, including the fact that olanzapine metabolism is strongly influenced by cytochrome inducers such as cigarette smoke. 44,45 This is widely represented among individuals with psychotic disorders and may therefore increase the likelihood of subtherapeutic doses when choosing a monthly administration.…”

Factors influencing concentrations of risperidone and 9‐hydroxyrisperidone in psychiatric outpatients taking immediate‐release formulations of risperidone

“…A retrospective analysis of 13,217 outpatients with psychotic disorders (Smith et al, 2021) suggested a complete nonadherence rate (undetectable blood level) of ~5% as a whole and a nonadherence rate of 2.4% in risperidone-treated patients. Another retrospective analysis of 40 outpatients treated with long-acting injectable antipsychotics (Hýža et al, 2021) also suggested a high incidence of plasma levels of drugs below their therapeutic reference ranges. Differed from inpatients, the medication compliance, blood testing time, and living habits of outpatients may all affect the plasma levels of antipsychotics.…”