Two-injection Start Strategy of Aripiprazole Once-monthly Injection: Current Evidence and Clinical Implications

Long-acting injectable antipsychotics (LAIs) are developed to overcome the limitations of oral antipsychotics (APs) and their use has been increasing in the treatment of various psychiatric disorders such as schizophrenia and bipolar disorder. LAIs are convenient to use and they were also found to enhance treatment adherence and continuation, leading to better clinical outcomes. Aripiprazole (ARP), a partial D2/5-HT1A receptor agonist, has been considered to have fewer adverse events than preexisting APs in terms of metabolic disturbance, sexual dysfunction, and mood instability. In this context, a once-monthly LAI formulation, aripiprazole once-monthly (AOM) has also been developed, and it is widely used in the real-world practice. However, it needs concurrent oral ARP administration for 14 days upon initiation, which may limit its practical use in routine practice due to the complexity of the regimen. Recently, the AOM two-injection start (TIS) strategy has been introduced, which allows rapid achievement of therapeutic plasma concentrations and stable drug levels without the need for a 2-week administration of oral ARP. This strategy may simplify treatment initiation with AOM as well as facilitate smoother transition from oral ARP to AOM in routine practice. Hence, this paper reviews the pharmacological basis, clinical evidence, clinical implications, and future prospects of the AOM TIS strategy in naturalistic treatment settings.