Tapered discontinuation vs. maintenance therapy of antipsychotic medication in patients with first-episode schizophrenia: Obstacles, findings, and lessons learned in the terminated randomized clinical trial TAILOR

Abstract

AimEvidence is insufficient regarding the consequences of discontinuing vs. maintaining antipsychotic medication in patients with first-episode schizophrenia. Our aim was to examine tapered discontinuation vs. maintenance treatment regarding remission of psychotic symptoms and impact on other areas.MethodsPatients included had a diagnosis of schizophrenia, were treated with antipsychotic medication, and were in remission of psychotic symptoms. Participants were randomized to tapered discontinuation or maintenance treatment with antipsychotic medication. Assessments were undertaken at baseline and after 1-year. The primary outcome was remission of psychotic symptoms without antipsychotic medication.ResultsThe trial was terminated due to insufficient recruitment. In total, 29 participants were included: 14 in the tapering/discontinuation group and 15 in the maintenance group. Adherence to maintenance treatment was poor. At 1-year follow-up, remission of psychotic symptoms without antipsychotic medication for 3 months was observed in five participants in the tapering/discontinuation group and two in the maintenance group.ConclusionDue to insufficient recruitment this study does not provide a conclusion on whether unfavorable outcomes or advantages follow tapering of antipsychotic medication. Recruitment and adherence to maintenance treatment encountered obstacles. Based on experiences from this trial, we discussed alternative study designs as consistent evidence is still needed on whether to continue or discontinue antipsychotic medication in remitted patients with first-episode schizophrenia.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000565-23/DK, EU Clinical Trials Register—EudraCT no. 2016–000565–23.

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

“…Three studies were double blind placebo-controlled trials [ 34 , 38 , 39 ]. Five studies had an open-label design, two with a blinded assessment of outcomes [ 9 , 40 ] and three without [ 36 , 37 , 41 ]. Follow-up durations were 1-year (five studies) [ 9 , 34 , 38 , 39 ], 18 months follow-up (one study) [ 36 ], and 2 years (two studies) [ 37 , 40 , 41 ].…”

“…Four RCTs (n = 350 participants) reporting on symptom severity assessed with either the PANSS or the SAPS/SANS were identified (Table 2) [6,9,35,41]. Antipsychotic discontinuation did not significantly increase positive symptoms (SMD 0.28; 95% CIs: À0.21, 0.77; I 2 = 76%), or negative symptoms (SMD -0.03; 95% CIs: À0.36, 0.30; I 2 = 50%) (Supplementary Figures 4 and 5).…”

“…The assessment of the certitude surrounding these alternative outcomes has remained conspicuously absent from prior reviews. Furthermore, it is worth noting that an additional study exploring antipsychotic discontinuation was published subsequent to the most recent review [ 9 ]. Despite its premature termination due to challenges in recruitment, this study remains a valuable source of potentially relevant data, particularly for outcomes where existing data are scarce, such as those beyond psychotic relapse [ 9 ].…”

“…months in the first trial and 3 in the second) (Figure2)[6,9,11]. Patients assigned to the antipsychotic discontinuation group European Psychiatry…”

Changing vistas of psychosis and antipsychotic drug dosing toward personalized management of antipsychotics in clinical practice.

“…Several discontinuation studies in recent onset patients are now on their way: the Reduce trial in Australia (Weller et al, 2019) and the Hamlett trial in the Netherlands (Begemann et al, 2020). The Tailor trial in Denmark was prematurely terminated due to a lack of participants (Stürup et al, 2022). Part of the problem with this trial was the reluctance of many patients to accept randomization with a chance to be assigned to either maintenance treatment or dose reduction, while they only opted for one of these.…”