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.