ABSTRACT
BACKGROUND: Fluphenazine decanoate licenced as a long-acting injectable (LAI) first-generation antipsychotic (FGA) was withdrawn from sale in 2018. This study evaluates if its withdrawal resulted in increased relapse rates of psychosis in an Irish patient cohort and examines which prescribed alternative antipsychotic medications were associated with more optimal outcomes. METHODS: Fifteen participants diagnosed with a psychotic disorder were included. A mirror-image study over 24-months' pre-and post-withdrawal of fluphenazine was conducted. Kaplan-Meier survival and proportional hazards analyses were conducted. The impact of alternate antipsychotic agents (LAI flupenthixol compared to other antipsychotic medications) was evaluated. Semi-structured interviews with participants examined subjective opinions regarding the change in their treatment. RESULTS: Seven participants (46.7%) relapsed in the 24-month period subsequent to fluphenazine discontinuation compared to one individual (6.7%) in the previous identical time-period (p = 0.035). Flupenthixol treatment was associated with reduced relapse rates compared to other antipsychotics (χ2 = 5.402, p = 0.02). Thematic analysis revealed that participants believed that the discontinuation of fluphenazine deleteriously impacted the stability of their mental disorder. CONCLUSION: The withdrawal of fluphenazine was associated with increased relapse rate in individuals previously demonstrating stability of their psychotic disorder. While acknowledging the limitation of small sample size, preliminary evidence from this study suggests that treatment with the first-generation antipsychotic (FGA) flupenthixol was associated with a lower risk of relapse compared to SGAs. Reasons for this lower risk of relapse are not fully clear but could be related to dopamine hypersensitivity with this treatment change.
ABSTRACT
Introduction: In this review, the authors discuss the role of long-acting injectable antipsychotics (LAIs) for schizophrenia, focusing on the effectiveness and new perspectives introduced by such treatment strategy. Despite their promising pharmacokinetic features and their potential advantages in medication adherence, clinical outcomes, and medical costs, LAIs are not habitually presented as an option for patients, especially in the early phase of schizophrenia.Areas covered: This review explores the panorama of available LAIs for the treatment of schizophrenia, first-episode of psychosis, approved indications, medical costs, medication adherence, side effects, effectiveness and differences between first-generation (FGA)-LAIs and second-generation (SGA)-LAIs.Expert Opinion: LAIs differ in terms of specific indications, approved injection sites, needle size, injection volume, injection interval as well as potential drug-drug interactions, and commonly reported adverse reactions. The approved indications have expanded beyond schizophrenia to include bipolar and schizoaffective disorder. SGA-LAIs are often preferred to FGA-LAIs. FGA-LAIs although are less chosen in new patients due to the induction of cognitive and extrapyramidal side effects, even if, on the other hand, many SGA-LAIs are burden by hyperprolactinemia and weight gain. After a review of the available evidence, insight is provided into the potential and current therapeutic opportunities offered by LAI antipsychotic formulations.
