Practical Guidance for the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia

Abstract

Schizophrenia is a severe mental illness causing a high degree of disability. First- and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described.

The Novel Antipsychotic Lumateperone (Iti-007) in the Treatment of Schizophrenia: A Systematic Review

“…Furthermore, the results of an open-label, non-randomized phase I Clinical Trial (ITI-007-025; NCT04709224), conducted to evaluate the safety, pharmacokinetics and tolerability of single doses of a subcutaneous long-acting injection of lumateperone that increase progressively, are still being processed [36]. This type of administration could help in the management of patients with low compliance, reducing the side effects that may arise from using other long-acting injectables (LAIs) due to its tolerability profile, which often results in treatment discontinuation [49]. However, additional data are required.…”

Long-acting injectable antipsychotics for the treatment of bipolar disorder: evidence from mirror-image studies

“…34 Indeed, the majority of SGA agents showing some benefit in the management of bipolar depression, such as quetiapine, lurasidone, and cariprazine, 35,36 do not have an available long-acting formulation, whereas the use of olanzapine LAI is rare for its poor tolerability. 12 In addition, since the pharmacological profile of FGA LAIs is characterized by a higher affinity for dopamine D 2 receptors, this would make them less appropriate for the long-term prophylaxis of depressive relapses in BD. 33 Finally, it remains unclear what is the clinical profile of subjects with BD who might most benefit from LAI treatment.…”

“…7 Depressive and manic relapses of BD increase the need for mental health outpatient and inpatient services utilization 8,9 and are often explained by poor treatment adherence. 10,11 For this reason, long-acting injectable antipsychotics (LAIs), approved by both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for schizophrenia maintenance treatment, 12 have been proposed as a therapeutic option for improving adherence also in BD. [13][14][15] Although LAIs represent a widely used off-label therapeutic option for BD, no LAI has been recommended by the EMA, while only Long-acting injectable antipsychotics for the treatment of bipolar disorder: evidence from mirror-image studies 2 journals.sagepub.com/home/tpp…”

Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review

“…Second generation drugs use different mechanisms to allow its gradual release, such as the microsphere system or suspension of nanoparticles in aqueous solution. Several LAI APs have been approved for use in patients with schizophrenia in the U.S. and Europe [58], although the availability of these drugs is not homogeneous between different countries. Unfortunately, in many low-and middle-income countries (LMICs) antipsychotics of any class are not always available [59], and actions to prioritize access to LAIs in LMICs should be carried out [60].…”