Guidance on the clinical understanding and use of long‐acting injectable antipsychotics in Schizophrenia: Hong Kong Consensus Statements

Abstract Aims There is increasing evidence showing the importance of long‐acting injectable antipsychotics in the management of schizophrenia, especially in terms of improving patient medication compliance. A panel of experienced clinicians in Hong Kong mapped out a set of consensus statements with an aim to facilitate the understanding and use of long‐acting injectable antipsychotics among local physicians. Methods Eight discussion areas regarding long‐acting injectable antipsychotics were selected by the chairman of the consensus group. A series of meetings were held for the panelists to discuss the published literature and their clinical experience, followed by the drafting of consensus statements. At the final meeting, each consensus statement was voted on anonymously by all members based on its practicability of recommendation in Hong Kong. Results A total of 12 consensus statements on the rational use of long‐acting injectable antipsychotics were established and accepted by the consensus group. Conclusion The consensus statements aim to provide practical guidance for Hong Kong physicians on the use of long‐acting injectable antipsychotics in schizophrenia patients. These statements may also serve as a reference for doctors in other parts of the Asia–Pacific region.

physicians. Furthermore, these statements can hopefully act as a reference for doctors treating patients with schizophrenia in other parts of the Asia-Pacific region. A consensus statement was accepted only if ≥80% of the members selected "accept completely" (option A) or "accept with some reservation" (option B) for practicability (Table 1).

| RE SULTS
A total of 12 consensus statements regarding the rational use of LAIs were established and accepted by the consensus group. Paliperidone LAI is prepared as an aqueous suspension of nanocrystals of paliperidone palmitate. 7,8 With an increased surface area, the nanomolecules allow for rapid release, which shortens the time to a steady plasma level of active paliperidone after intramuscular injection. 7 This kinetic property can also facilitate an initial loading regimen to reach therapeutic antipsychotic levels in schizophrenia patients, without the need for oral antipsychotics (oral APs). 8 As per the results of some placebo-controlled trials, 9 starting or loading doses (ie, 150 mg equivalents [mg eq.] on day 1 and 100 mg eq. on day 8) are recommended to be administered in the deltoid muscle.
Maintenance doses (ie, 25-150 mg eq/4 wk) can be administered in the deltoid or gluteal muscle.
As for RLAI, it is a water-based formulation of risperidone-impregnated microspheres, which make loading impossible, and a lag period of about 3 weeks is observed during the drug-releasing process. 7,8 Therefore, at least 3 weeks of supplemental oral APs should be prescribed initially to maintain a sufficient drug level. 7 Voting results: A: 63%, B: 37%, C: 0%, D: 0%, E: 0% Two studies found that, compared with oral risperidone, RLAI may enhance the development of intracortical myelin and improve the myelination trajectory in first-episode schizophrenia patients, possibly leading to a better cognitive function. 13,14 An open-label trial revealed that a switch from haloperidol decanoate to RLAI may boost cognitive performance in patients. 15 A review also found that SGA LAIs can be administered at an early stage of schizophrenia to better preserve cognitive capabilities of patients. 16 In an in vitro study, 17 risperidone and paliperidone were shown to possibly protect against apoptosis, while haloperidol induces it.
The difference may be associated with their capacity to induce extrapyramidal symptoms. However, more studies are required to confirm the neuroprotective effect of SGA LAIs. Voting results: A: 63%, B: 37%, C: 0%, D: 0%, E: 0% As shown in the Finnish cohort study on patients discharged from hospitalization due to schizophrenia, 33 those treated with LAIs had a significantly lower risk of re-hospitalization compared with those treated with oral APs. An observational study also found that RLAI was correlated with reductions in both the number and days of hospitalization in schizophrenia patients compared with oral risperidone. 32 The guidelines set by a group of French experts on psychiatry recommend SGA LAIs as first-line treatment for patients receiving outpatient care. 25 Based on the available evidence, the consensus group recommend that LAIs should be prescribed for patients in the outpatient setting who have signs of relapse and potential adherence issues, so as to reduce their hospitalization risk. In conclusion, the consensus statements were formulated based on the available evidence from individual studies, expert consensuses, and major overseas guidelines, combined with the insights of the panelists. These statements aim to provide a practical guidance for local physicians on the use of LAIs in patients with schizophrenia.

ACK N OWLED G M ENTS
All authors contributed to selection and review of the relevant lit-

CO N FLI C T O F I NTE R E S T S
The authors declare no conflict of interest.