While long-acting injections (LAI) have arrived in Japan as a second-generation antipsychotic drug and LAI therapy for the symptom-stabilization phase is garnering attention, deaths associated with paliperidone (PAL)-LAI were sensationally reported, attracting interest regarding the safety of LAIs. In writing this report, an opportunity to oppose LAI usage was provided, so we raise the following three issues concerning the usage of the second-generation antipsychotic LAI for the symptom-stabilization phase.
 1) Particularly notable adverse reactions of LAI are those acutely developed and in some cases fatal, including malignant syndrome, diabetic ketoacidosis, torsade de pointes due to prolonged electrocardiogram QT, and leukopenia. All antipsychotic drugs come with the risk of such adverse reactions, and since the occurrence of adverse reactions cannot be predicted prior to administration, once they have developed, the offending drugs should be immediately reduced or discontinued to remove the drug from the body; however, since this process cannot be followed with LAIs, such fatal adverse reactions may be protracted. Moreover, in the US, adverse reactions from post injection delirium/sedation syndrome (PDSS) have been reported in relation with olanzapine (OLZ)-LAI. This is a disease state in which the drug rapidly flows into the blood following LAI intramuscular administration along with an acute increase in blood level, leading to significant sedation(lethargy in some cases) and/or serious symptoms accompanied by delirium; therefore, in order to minimize these risks, the US FDA has made it mandatory to use a monitoring system referred to as REMS (Risk Evaluation and Mitigation Strategy) for OLZ-LAI. Whether or not the phenomenon occurs only with OLZ-LAI remains to be seen, so careful attention must be paid.
 2) In Japanese psychiatric clinical sites, the current situation is that monitoring of adverse reactions for antipsychotic drugs, particularly with outpatients, is not sufficiently carried out. Under such circumstances, there remain doubts when it comes to advocating looking to replace oral drugs with LAI in the symptom-stabilization phase.
 3) Replacing oral drugs with LAI in the symptom-stabilization phase significantly increases treatment costs as well as increasing the number of hospital visits. This increase in treatment cost and number of visits may have a large impact on the adherence of the patients to the drugs.
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