Dose-tapering trajectories in patients with remitted psychosis undergoing guided antipsychotic reduction to reach minimum effective dose

Abstract

Background: Patients with remitted psychosis wish to reduce antipsychotic doses yet facing increased risks of relapse. Examining dose-tapering processes may provide insights to re-evaluate the risk-to-benefit balance. We aimed to depict and subgroup tapering trajectories, and explore factors associated with different dose-reduction patterns.

Methods: A 2-year open-label randomized prospective comparative trial from August 2017 to September 2022 in Taiwan. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomizing a proportion to conduct guided dose reduction. We depicted the trajectories of individual patients and named subgroups based on dose-tapering patterns. Predictors of baseline characteristics for designated subgroups were examined by logistic regression analysis; changes in outcomes were compared by paired t-test.

Results: Fifty-one patients undergoing guided dose reduction, 18 (35.3%) reduced 4 steps consecutively (sequential reducers, SR), 14 (27.5%) reduced 1 to 3 steps (modest reducers, MR), 3 (5.9%) re-escalated to previous level (alert reducers, AR), 7 (13.7%) returned to baseline level (baseline returners, BR), 6 (11.7%) relapsed (failed reducers, FR) and 3 (5.9%) withdrew without relapse (early exits, EE). Patients with a history of relapse assumed a conservative dose-tapering pace; only the SR subgroup exhibited significant improvements in functioning and quality of life while failing to identify variables for predicting who would become SR or FR.

Conclusions: Guided dose reduction comprises dynamic processes with differences between individual trajectories. The proposed naming of dose-tapering patterns/subgroups provides a framework depicting patients undergoing dose-tapering. Longer-term observation and more flexible tapering approaches are anticipated to reveal favorable outcomes.

Keywords: antipsychotics; minimum effective dose; quality of life; tapering; trajectory.

Figure 1.

Diagram of trial flow chart.

Figure 2.

Patterns of dose tapering trajectories. Sequential reducers (SR), those who were able to taper doses at each designated timepoint successfully for four steps in 2 years; Modest reducer (MR), those who took a cautious pace in tapering, thus they only reduced 1 to 3 steps, with no re-escalation to previous step, during 2 years; Alert reducer (AR), those who have had reduced at least two steps yet re-escalated dose back to the level between their baseline dose and the lowest dose they have reached during the course of dose tapering; Baseline returner (BR), those who have tapered at least 1 step but returned to baseline dose for concern about risks of relapse and were able to stay in remission throughout the course; Failed reducer (FR), those who had a relapse during dose tapering and were in need of a dose higher than their baseline level; Early exit (EE), those who left the trial after tapering at least 1 step without relapse before the end of 2-year follow-up. AR, BR, and MR were collapsed as conservative reducers (CR) in further analyses.