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

Abstract

Aims Patients with psychosis intend to discontinue antipsychotic treatment for various reasons. As antipsychotic discontinuation involves a high risk of relapse, maintenance treatment is recommended by mainstream opinion even when remission is attained. To optimize the risk‐to‐benefit ratio of long‐term antipsychotic treatment, we proposed an operationalized guided dose‐reduction algorithm to serve as an intermediate approach as to achieve the lowest effective antipsychotic dose and better functioning for patients with remitted psychosis. Methods Outpatients with a history of schizophrenia‐related psychotic disorders currently under stable medications and symptoms are eligible to register in this protocol. Patients intending for dose reduction are randomized into 2:1, guided dose reduction group (GDR) versus maintenance treatment group (MTG1). Eligible patients who do not intend to reduce antipsychotics serve as naturalistic maintenance controls (MTG2). The GDR patients reduce no more than 25% of their baseline antipsychotic dose, with at least a 6‐month stabilization period before reducing another 25% of their last dose. The timing of the next dose reduction will be determined by shared decision‐making with the patient. Following a dose reduction, the patients will receive three consecutive monthly monitoring; otherwise, they receive treatment as usual. Discussion By employing this pragmatic‐based protocol, patients are empowered to evaluate their readiness for next dose reduction attempt. We would like to test in real‐world situations if stable patients can reduce antipsychotics not at the expense of an increased risk of relapse, so as to optimize the balance between risk‐to‐benefit ratios of long‐term antipsychotic treatment.

Pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first‐episode schizophrenia: Japanese Society of Clinical Neuropsychopharmacology treatment algorithms

“…The algorithm does not recommend discontinuation of antipsychotics for the following reasons. First, it is reported that the discontinuation of antipsychotics is associated with a higher risk of relapse even in first‐episode schizophrenia or psychosis (Kishi et al., 2019 ; Leucht et al., 2012 ), several studies are ongoing to address this topic (Begemann et al., 2020 ; Liu et al., 2021 ; Moncrieff et al., 2019 ; Stürup et al., 2017 ; Weller et al., 2019 ). Second, there are no established clinical predictors for successful discontinuation of antipsychotics (Bowtell et al., 2018 ).…”

Discontinuing Antipsychotic Medication After Remission from First-Episode Psychosis: A Survey of Psychiatrists’ Attitudes in Taiwan

“…Such proactive attitudes are most likely related to their knowledge regarding the investigators’ ongoing project of antipsychotic dose reduction. 49 …”

“… 43 In the present study, among the six items endorsed by significantly more Taiwan respondents ( Table 5 ), nearly 80% selected patient’s readiness and willingness to be an important criterion for medication discontinuation, a factor taken into account by Liu’s protocol. 49 …”

Challenging the Minimum Effective Antipsychotic Dose During Maintenance: Implications From 10-Year Follow-Up of First Episode Psychosis

“…Echoing the notion that “Less (antipsychotic) Is More (benefiting)” in terms of pharmacotherapy following remission from the first episode of psychosis proposed by McGorry et al ( 67 ), our evidence suggests that at least a substantial proportion of patients could do well under a low, even a very low, dose of antipsychotic medication. Inspired by such encouraging clinical observations, we proposed a protocol to conduct a carefully guided antipsychotic dose-reduction trial for patients remitted from psychosis ( 68 ). We anticipate gaining more solid evidence to consider revising the schizophrenia long-term treatment guidelines to include “on when and how slowly to reduce antipsychotics, and in whom it is appropriate to eventually stop them” ( 69 ).…”