Long-Acting Injectable Antipsychotics: A Systematic Review of Their Non-Systemic Adverse Effect Profile

Abstract

Introduction Long acting injectable (LAI) antipsychotics are commonly used in the treatment of schizophrenia to improve adherence and clinical outcomes. Concerns have been reported in relation to their non-systemic or injection site adverse effect profile. As such, this study aims to review and evaluate all evidence reporting injection site adverse effects with LAI antipsychotics. Methods An electronic search was systematically conducted through four databases (PubMed, Embase, SCOPUS, Cochrane) in order to identify studies investigating injection-site reactions associated with LAI antipsychotics. Unpublished studies such as conference proceedings and clinical trial registries were also searched. The search was limited to literature published in English without year limits. Results Of a total of 189 citations that were identified from the electronic database search, 12 were selected for inclusion in this review. Various injection site reactions were reported in these studies, including pain, bleeding, and swelling. Overall, the studies reported a low incidence of these injection site reactions. Only a minority of the included articles compared injection site reactions between different LAI antipsychotics. Conclusion Injection site pain was the most commonly reported injection site adverse effect across all articles reviewed. The low incidence of injection site adverse effects associated with LAI antipsychotics indicates that these formulations appear to be well tolerated by patients. More head-to-head trials comparing second generation LAI antipsychotics are needed.

Importance of Long-Acting Injectable Antipsychotic Preparation, Administration, and Injection Site Tolerability: A Focus on Paliperidone Palmitate Once-Every-6-Months Formulation

“…Repeated large-volume administrations of these oil-based LAI formulations are shown to cause muscle granuloma, fbrosis, and accumulation of oil in some patients [21], which may contribute to poor treatment adherence and thus, medication discontinuation and symptomatic relapse [22]. To prevent leakage from injection sites and reduce the incidence of injection site adverse efects associated with oil-based LAI antipsychotics, the Z-track technique is often recommended [12].…”

“…Misconceptions or concerns about side efects, fear of injections, and the stigma that LAIs are a last resort or punishment [9] may also be a deterrent for some patients and their caregivers. Unlike oral antipsychotic medications, LAIs may be associated with a range of potential injection site reactions such as injection site pain, induration, redness, and tenderness [12]; however, these adverse events (AEs) are typically mild in severity. Te frequency of injection site reactions and pain after administration of LAIs can be infuenced by several factors, including the type of vehicle used (oil vs. aqueous based), injection volume, the site of injection, dose preparation and administration technique, and patient history with LAIs [12].…”

Long-Acting Injectable Antipsychotics—A Review on Formulation and In Vitro Dissolution

“…These groups differ in terms of strength in relation to the negative symptoms and the enhancement of cognitive functions. Both groups differ regarding tolerability, toxicity, and the risk for tardive dyskinesia [ 37 ].…”

“…[ 36 ]. They are intended for individuals requiring a long-term antipsychotic therapy lasting at least several months [ 37 ].…”

Aripiprazole Plasma Concentrations Delivered from Two 2-Month Long-Acting Injectable Formulations: An Indirect Comparison

“…5,7 Real-world evidence suggests that, compared with oral antipsychotics, long-acting injectable (LAI) formulations are associated with significant improvements in treatment adherence for schizophrenia, as well as BP-I, 8,9 and promote more regular contact between a patient and their healthcare team. 10 In addition, due to the slow release of antipsychotic medication from the LAI formulations, 11 therapeutic plasma drug concentrations are sustained for longer and decrease more slowly than with oral formulations. 12 Patients receiving LAI treatment have reported their preference for LAIs over oral antipsychotics, 13 finding the injections "easier to remember" and stating they have a "more normal life".…”