Can antipsychotic dose reduction lead to better functional recovery in first‐episode psychosis? A randomized controlled‐trial of antipsychotic dose reduction. The reduce trial: Study protocol

Abstract

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. Aim The primary aim of the study is, in a population of young people with first‐episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence‐based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24‐months follow‐up. Methods Our single‐blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2‐year period in 180 remitted first‐episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow‐up. Results This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. Conclusion This study will provide evidence as to whether an antipsychotic dose‐reduction recovery treatment leads to improved functioning and safer outcomes in first‐episode psychosis patients. In addition, it will be the first‐controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial

“…Currently, similar trials are being conducted: the TAILOR trial [49] (Denmark), the RADAR study (research into antipsychotic discontinuation and reduction; UK), the reduce trial [50] (Australia), and "A Guided Dose Reduction Trial for Patients with Remitted Psychosis" [51] (Taiwan).…”

The longitudinal effect of antipsychotic burden on psychosocial functioning in first-episode psychosis patients: the role of verbal memory

“…Moreover, AP discontinuation has been considered regardless of the risk of the underlying disorder (Moncrieff, 2006) but gradual reduction is generally recommended in FEP stabilised patients rather than abrupt 4 weeks discontinuation as it reduces relapse rates (Landolt et al, 2016; Viguera, Baldessarini, Hegarty, van Kammen, & Tohen, 1997; Wunderink et al, 2013). We may conclude that the clinician should put into balance patient's preferences and risk of relapse considering that patients value social functioning over reduction of their positive symptoms (Gunnmo & Bergman, 2011) while recent literature has suggested reviewing current recommendations for AP lengths of 2–5 years to more than a decade in some cases (Andreasen, Liu, Ziebell, Vora, & Ho, 2013; Weller et al, 2018). Although speculative, this length would likely depend on risk predictors detected in the initial stages (Suvisaari et al, 2018) or present prior to the illness onset (Fusar-Poli et al, 2010).…”

Protocol of guided antipsychotic reduction to reach minimum effective dose (GARMED) in patients with remitted psychosis based on pragmatic design

“…This study protocol is based on much more pragmatic than explanatory considerations, as checked by the PRECIS‐2 (Pragmatic‐explanatory continuum indicator summary) criteria (Loudon et al, 2015; Figure 2). Our flexible guided antipsychotic dose reduction algorithm has some subtle, but pivotal, differences compared to other clinical trials on similar populations (Begemann et al, 2020; Moncrieff et al, 2019; Sturup et al, 2017; Weller et al, 2018). First, the proportion of each dose reduction (no more than 25%) is the same as proposed by other designs, while our pace in dose reduction is much slower (at least a period of stabilization for 6 months the pre‐requisite for the next dose reduction, compared to 1–3 months required by other trials).…”