The impact of fluphenazine withdrawal: a mirror-image study

Abstract

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Background: Fluphenazine decanoate licenced as a long-acting injectable (LAI) first-generation antipsychotic (FGA) was withdrawn from sale in 2018.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.