Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents

Abstract

Schizophrenia is a chronic medical condition with periods of remission and relapses over a patient's lifetime. Antipsychotic medications represent the mainstay of treatment for this disease. Long-acting injectable (LAI) formulations of antipsychotics are an attractive alternative to their oral counterparts, as they enhance patient adherence. A number of second-generation antipsychotics (SGAs) are available in LAI formulations. These include paliperidone, aripiprazole, olanzapine, and risperidone. This article reviews the most recently developed and approved of these formulations-aripiprazole monohydrate, aripiprazole lauroxil, and paliperidone palmitate. While all were initially available as once-monthly formulations, a paliperidone palmitate 3-monthly injection formulation has been approved and is the first LAI agent to extend the dosing administration beyond the typical monthly time period. In addition, aripiprazole lauroxil every 6-week and 8-week administration preparations have been developed. LAI preparations of the SGAs have all demonstrated superiority over placebo and are comparable to their oral counterparts in terms of safety and tolerability, if injection site reactions are not taken into account. First-generation antipsychotic LAI preparations (e.g., haloperidol decanoate) have recently been compared with SGA LAI agents, and both formulations demonstrated comparable efficacy with the expected adverse events seen with each drug. Despite their availability, barriers to the use of LAIs remain. Education of both patients and clinicians on the use of LAI formulations and the continued development of these agents are important steps in ensuring these medications are available to the patients they would be most likely to benefit.

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…As the few direct comparison studies of depot/LAI antipsychotic preparations have not revealed much difference in terms of efficacy between those tested (Li et al, 2011; McEvoy et al 2014; Pandina et al, 2011), the nature of the side-effect burden is probably the primary criterion for choosing a particular medication. The adverse effects include uncomfortable local reactions at the injection site, characterised by pain, inflammation and induration, which have been estimated to occur in up to 15–20% of patients a year (Bloch et al, 2001; Hay, 1995; Jones et al, 1998), although lower rates with LAI SGAs have been reported more recently (Atkins et al, 2014; Jann and Penzak, 2018). Jones et al (1998) suggested that the risk of such reactions with FGA depot/LAIs might be minimised by the use of low-volume preparations and increasing the interval between injections.…”

Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region

“…There has been hope that use of long‐acting injectable (LAI) or depot preparations of antipsychotic medications would increase long‐term treatment‐adherence and enhance the effectiveness of treatment. Such agents started with esters of fluphenazine and haloperidol in the 1960s and 1970s, followed by additional esters as well as agents made long‐acting by other pharmacological mechanisms (Baldessarini, 2013; Haddad, Brain, & Scott, 2014; Jann & Penzak, 2018; Johnson, 2009). There was a resurgence of interest in LAI antipsychotics after the launch of risperidone in a LAI form based on its incorporation into slowly hydrolyzed carbohydrate microspheres (Sampson, Hosalli, Furado, & Davis, 2016).…”

Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population

“…Schizophrenia is a widespread mental disorder with periods of remission and relapses over a patient's lifetime (van Os and Kapur, 2009;Jann and Penzak, 2018), and long-term treatment with antipsychotic drugs is often required (Kahn et al, 2015). The lifetime prevalence of schizophrenia in Chinese population is 0.9% (Huang et al, 2019).…”