Long-Acting Injectable Formulations of New-Generation Antipsychotics: A Review from a Clinical Perspective

Abstract

Antipsychotics are the mainstay of the long-term treatment of patients with schizophrenia. In this context, the evidence also supports the effectiveness of long-acting injections (LAIs) or depots of antipsychotics regarding their relapse-preventing properties. When a LAI formulation of risperidone was launched as the first second-generation depot, there was a renaissance of interest in these formulations. In the meantime, olanzapine, paliperidone, and aripiprazole have been approved by regulatory authorities as LAIs in various countries. All studies using the new-generation depots have shown a clear advantage over placebo regarding relapse prevention and symptom reduction. Safety profiles of the long-acting compounds are comparable to their oral formulations with the exception of olanzapine pamoate injections, which can sometimes lead to a post-injection delirium. Despite the fact that many treatment guidelines recommend LAI antipsychotics as an important treatment option for the long-term management of schizophrenia, they are still most frequently used in chronically ill patients with considerable compliance problems. It is imperative to overcome this indication bias in order to be able to utilize all available treatment options in the long-term management of schizophrenia. There is little evidence on comparisons between LAIs and their oral mother compounds, and even less concerning effectiveness comparisons between different depots. The purpose of this manuscript is to review the recent clinical evidence on new-generation depot antipsychotics.

The effects of switching from oral to LAI antipsychotic treatment on subjective experience of schizophrenic and schizoaffective patients: Preliminary results

“…Th ese preliminary results are consistent with previous reports indicating the switch from oral to LAI antipsychotic treatment as a safe and eff ective intervention in clinically stable schizophrenic and schizoaff ective patients (Ju et al 2014;Kaplan et al 2013;Lafeuille et al 2013;Rauch and Fleischhacker 2013). Th is seems to be further confi rmed by the almost-complete patients ' adherence to our protocol and by the lack of adjustments of concomitant treatments found in our study.…”

“…Similarly, while the benefi ts of second-generation over fi rst-generation antipsychotics (SGA vs FGA) (Crossley et al 2010;Leucht et al 2013) and of long-acting injectable over oral (LAI vs oral) antipsychotic formulations (Ju et al 2014;Kaplan et al 2013;Lafeuille et al 2013;Rauch and Fleischhacker 2013) in terms of better effi cacy, prevention of relapse, tolerability, and drug kinetics and dynamics have been widely demonstrated, less research have been devoted to the evaluation of the subjective impact of switching antipsychotic administration from oral to LAI (Iyer et al 2013;Kaplan et al 2013;Kirschner et al 2013;Rosa et al 2012).…”

Aripiprazole (ABILIFY MAINTENA®): A Review of Its Use as Maintenance Treatment for Adult Patients with Schizophrenia

“…Aripiprazole LAI was superior to placebo, and noninferior to oral aripiprazole, in delaying the time to (impending) relapse, as well as in reducing relapse rates. Furthermore, it was suggested that the actual benefit of aripiprazole LAI over oral aripiprazole in clinical practice may be underestimated in the structured setting of a clinical trial [21,40]. Firstly, patients willing and able to participate in a clinical trial are, overall, less likely to be nonadherent to their medication compared with patients generally found in clinical practice.…”

“…haloperidol and fluphenazine) and atypical (e.g. risperidone, paliperidone, olanzapine and aripiprazole) agents [20,21]. Besides potentially improving adherence, other advantages of long-acting formulations include relieving patients of the need to take daily medications, the signalling of nonadherence to healthcare workers if patients fail to attend drug administration appointments, and signalling when relapse has occurred despite medication [13,22].…”

Post-Injection Delirium/Sedation Syndrome in Patients Treated with Olanzapine Pamoate: Mechanism, Incidence, and Management

“…OLAI and oral olanzapine display a very similar profile concerning efficacy and adverse effects [16][17][18][19][20]. However, when using OLAI (compared with the use of other available LAIs) there is a 0.07 % chance of developing a postinjection delirium/sedation syndrome (PDSS) after injection [21], which requires a risk-management plan.…”