Combination of Long-Acting Injectable Antipsychotics in the Treatment of Psychiatric Disorders—A Systematic Review of the Literature and Case Series

Abstract

BackgroundThe treatment of refractory schizophrenia is complex, and compliance with oral treatment, including clozapine, can be challenging at times. The purpose of this case series and literature review article is to evaluate the efficacy of the combined use of 2 different long-acting injectable antipsychotics (LAIAs) on the number of psychiatric hospitalizations and emergency department visits. There are currently few data to support this treatment option, despite the frequent use of combinations of oral antipsychotics.MethodsWe extracted the data from 8 different patients who received combination LAIAs from 1 hospital setting. We evaluated the frequency of hospitalization and emergency department visits before and after treatment with a mirror-image study design. A systematic review of existing literature was included to find all previously reported cases of combination LAIAs.ResultsThe frequency of hospitalizations was greatly reduced after the initiation of combination LAIA treatment in the majority of the cases at study site, as well as in the literature review. The number of ED visits was not as clearly affected. In the literature review, combinations of 2 LAIAs with different mechanisms of action were often documented. Symptom scores were also reduced in most reviewed cases.ConclusionsCombinations of LAIAs seem to be promising as a treatment option for refractory psychotic disorders. This combination could be a treatment option for patients with limited alternatives, such as clozapine resistant or not eligible. The higher risk of adverse effects and long-term risks are not well documented.

Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review

“…A total of 15 studies was included in this review. Of these, nine were case reports [84,[86][87][88][89][90][96][97][98], four case series [85,[99][100][101], and two were observational retrospective studies [94,95]. No randomized clinical trial has been found that met the inclusion criteria.…”

“…Of these, 29 (23.57%) were male and 11 (8.94%) female; no data about gender were available for the remaining 94 subjects (63.48%), who were all included in one study [95]. The sample's age ranged from 16- [101] to 67- [85] years-of-age. All patients received a diagnosis of schizophrenia (N = 68) [84][85][86][87]89,[94][95][96][97][98][99][100][101] or schizoaffective disorder (N = 43) [85,88,90,94,95], with the exception of 12 patients, whose main diagnosis was represented by bipolar disorder (N = 6), organic diseases (N = 2), and intellectual disability (N = 4) [95].…”

“…All patients received a diagnosis of schizophrenia (N = 68) [84][85][86][87]89,[94][95][96][97][98][99][100][101] or schizoaffective disorder (N = 43) [85,88,90,94,95], with the exception of 12 patients, whose main diagnosis was represented by bipolar disorder (N = 6), organic diseases (N = 2), and intellectual disability (N = 4) [95]. The duration of illness extended from two [85] to thirty-two [88] years; in two cases, patients treated with dual LAI APs were at their first episode of psychosis [101]; however, this information is not consistently reported across studies [84,89,94,95,97]. The most frequently reported comorbidities were substance use disorder (SUD) and personality disorders (PD) [85,101].…”

“…The duration of illness extended from two [85] to thirty-two [88] years; in two cases, patients treated with dual LAI APs were at their first episode of psychosis [101]; however, this information is not consistently reported across studies [84,89,94,95,97]. The most frequently reported comorbidities were substance use disorder (SUD) and personality disorders (PD) [85,101]. Other physical comorbidities included hyperlipidemia [86,98], obesity [86,98], hypertension [85,86], acne inversa [98], and Wolf-Parkinson-White syndrome [85].…”

“…After a full text reading, a total of 414 articles were removed, as they did not meet the inclusion criteria. Moreover, six papers were added by snowballing and citation checking [84][85][86][87][88][89]. Notably, one article was included even though it is a review [85], as it also includes relevant case reports; furthermore, one article written in German resulting from PubMed database [90] and one written in Spanish [87] were also included in the final analysis, as all the relevant data were available in English in another record [85].…”