This review critically examines the clinical utility, efficacy, and tolerability of fluphenazine long-acting injectable (LAI) relative to contemporary alternatives. It further evaluates whether fluphenazine LAI confers substantive advantages over other available formulations for the management of schizophrenia, particularly in light of its long-standing use.

The extant literature demonstrates that the tolerability and side effect profile of fluphenazine LAI are comparable to other FGA LAIs but likely less favorable than available second-generation antipsychotic (SGA) LAIs. Although fluphenazine trends towards the higher end of the efficacy scale in meta-analyses, there is a lack of robust evidence showing a true statistical superiority for relapse prevention in schizophrenia. Social determinants of health (SDoH), such as race and economic factors, significantly influence its prescribing patterns. Fluphenazine LAI continues to be utilized primarily due to its low cost and widespread clinical familiarity rather than evidence-based superiority in efficacy or tolerability. Its prescribing is disproportionately influenced by healthcare inequities and resource limitations. Clinicians should employ a rigorous, individualized approach to antipsychotic selection, incorporating shared decision-making and patient education to ensure optimal therapeutic outcomes.