Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review

Abstract

Objective Antipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation, to develop guidelines for antipsychotic discontinuation in such patients. Methods We reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results Most studies had low to very low quality, and two had moderate quality. All studies, except one, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19–82% at 1-year follow-up) than the treatment maintenance group compared to the maintenance group. Based on expert opinion and GRADE evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders. Conclusions Currently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients, using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.

The effects of antipsychotic discontinuation or maintenance on the process of recovery in remitted first-episode psychosis patients – A systematic review and meta-analysis of randomized controlled trials

“…Statistical heterogeneity was explored using subgroup analysis. Subgroup analyses were done to explore the effect of risk of bias (high, some concerns, and low risk), types of antipsychotics (first-generation, second-generation, or mixed), use of injectable antipsychotics (oral, long-acting injectable, mixed), mean antipsychotics defined daily doses (DDD) used (low [<0.9 DDD], normal [≥0.9 and <1.1 DDD] and high [≥1.1 DDD]), sex (female, male, or mixed), discontinuation methods (abrupt and gradual discontinuation), and remission duration (short [≤12 months], medium [>12 months and ≤18 months], and long duration [>18 months]) [ 3 , 26 , 27 ]. The selection of these subgroup analyses was informed by the understanding that the characteristics of antipsychotics, study quality, duration of remission, and discontinuation strategies may influence recovery outcomes.…”

“…Antipsychotics have proven efficacy in treating first-episode psychosis (FEP) as they allow achieving a rate of symptomatic remission at 12 months of approximately 54% [ 1 ]. However, uncertainty persists regarding the optimal duration of treatment beyond the initial episode, guidelines recommending treatment maintenance for periods of at least 1–5 years, depending on the guidelines considered [ 2 , 3 ]. Two meta-analyses of randomized controlled trials (RCTs) published in 2018 found a higher rate of psychotic relapse in patients discontinuing treatment [ 4 , 5 ].…”

“…However, the level of certainty for this finding was not presented in those articles. One narrative review in 2022, using the GRADE approach, concluded with low certainty of evidence that antipsychotic discontinuation increases the risk of psychotic relapse (risk difference 26%), although nearly half of the patients in whom treatment was discontinued did not experience relapse [ 3 ].…”

Network biomarkers in recovered psychosis patients who discontinued antipsychotics

“…For individuals who achieved both symptomatic and functional recovery, there is a need to determine when and how antipsychotic medication should be discontinued. We recently published “Guidelines for discontinuation of antipsychotics in patients who recover from first-episode schizophrenia spectrum disorders” [ 5 , 6 ]. In the guidelines, we suggested using stricter criteria when deciding whether to discontinue antipsychotics, rather than Andreasen’s criteria (which are most frequently used in discontinuation trials) [ 7 ].…”

“…They showed altered functional connectivity (FC) [ 11 ], as well as changes in the activities of specific brain regions, while the patients performed tasks [ 10 , 12 ]. However, the participants in those studies did not meet our strict criteria for full recovery [ 3 , 5 ]. SZ has been explained in terms of aberrant interactions among brain regions, leading to the degeneration of brain networks; this degeneration is referred to as disconnection syndrome [ 13 – 15 ].…”