Effectiveness of Long-Acting Injectable Antipsychotics in Schizophrenia: A Literature Review and Bayesian Meta-Analysis Informing Economic Considerations

Abstract

BACKGROUND: Although the use of long-acting injectable antipsychotics (LAIs) is considered an important option in the management of schizophrenia two recent meta-analysis, which aimed to compare LAIs vs oral antipsychotics (OAPs) in terms of relapse rate, showed discordant results.AIM: To investigate factors affecting the efficacy of antipsychotics in terms of relapse prevention in the real-world and to estimate the management cost of an episode of relapse.METHODS: We conducted a literature search using MEDLINE/PubMed with the aim to extract efficacy, effectiveness and adherence data of LAIs and OAPs. The primary outcome was the relative risk (RR) of relapse between two strategies. The extracted RR were included in a series of Bayesian statistical models based on the starting hypotheses. The RR rates obtained from the meta-analysis have been used as input for an economic evaluation of the total costs associated with the management of the patient with schizophrenia from the Italian NHS perspective.RESULTS: The literature search identified 34 studies which met the inclusion criteria and were analyzed. According to the model that best explains the data, in the real-world setting the effectiveness with LAIs is greater than with OAPs, with a more pronounced effect for SGAs than for FGAs. Taking into account generation, route and frequency of administration, the RR decreased with lower administration frequency, with SGA LAI administered once every 90 days which is associated with the greatest reduction in the risk of relapse (-85%). When the results of the meta-analysis are used to feed an economic evaluation the results show that the SGA administered every 90 days is the strategy with the least expected cumulative cost both at 1 (€ 3,509) and 5 years (€ 19,690).CONCLUSION: SGA LAIs administered every 90 days seems to be the best option for the treatment of patient with schizophrenia from both the clinical and economic perspectives.An erratum to this article is available online at: https://doi.org/10.7175/fe.v20i1.1406

Optimizing Treatment of Schizophrenia: Clinical and Economical Potential for Patient Switching to Long‑Acting Injectables

“…The meta-analysis methodology has been described elsewhere [7]. In accordance with these methods and rationale, we conducted a literature search using MEDLINE/PubMed (last access May 20, 2022) with the aim to extract efficacy and effectiveness of LAIs and OAPs.…”

“…Literature search and selection were conducted using the same criteria detailed in the previous paper [7]. The outcome was the hazard ratio (HR) of relapse between the two strategies.…”

“…The other chapter of expenditure, i.e., relapses management costs, was estimated for both scenarios by multiplying the events rate resulting from the updated meta-analysis for considered regimens by the cost incurred to manage the event. According to Expert opinion, the burden associated with a relapse generally included the entire management pathway, especially the hospitalization for the acute phase lasting an average of 10-15 days (quantified using regional tariffs) and the subsequent stay in residential facilities for rehabilitation for an average of 30 days: the resulting mean cost per episode was € 10,500 [7].…”

“…A Bayesian hierarchical model was designed on the basis of the hypotheses we wanted to test: in a real-world setting, LAIs are associated with better adherence compared to OAPs. In an experimental setting, a LAI and the same OAP have similar efficacy and adherence, whereas in the real-world, a net increase in the efficacy of LAI can be noted; this phenomenon has a gradient and becomes more evident when the administration is less frequent [7]. We conducted a comprehensive literature search with the aim to extract the relative risk of relapse between strategies differing in terms of active ingredient and/or administration route and/or inter-administration interval.…”

“…A few years ago, this inconsistency led us to further investigate these dynamics using a Network Metanalysis (NMA) to estimate the magnitude of the clinical effect associated with improved adherence with LAI [7]. A Bayesian hierarchical model was designed on the basis of the hypotheses we wanted to test: in a real-world setting, LAIs are associated with better adherence compared to OAPs.…”