TAILOR – tapered discontinuation versus maintenance therapy of antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder in remission of psychotic symptoms: study protocol for a randomized clinical trial

Abstract

BackgroundThe aim of the TAILOR trial is to investigate the effect of closely monitored tapering/discontinuation versus maintenance therapy with antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder and with minimum 3 months’ remission of psychotic symptoms.Methods and designTwo hundred and fifty patients will be included from the psychiatric early intervention program, OPUS, in two regions in Denmark. Inclusion criteria are: ICD-10 diagnoses schizophrenia (F20, except F20.6) or persistent delusional disorder (F22), minimum 3 months’ remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine). The patients will be randomized to maintenance therapy or tapering/discontinuation with antipsychotic medication in a 1-year intervention. The tapering/discontinuation group will be using a smartphone application to monitor early warning signs of psychotic relapse. Patients will be assessed at baseline, 1-, 2- and 5-year follow-up regarding psychotic and negative symptoms, side-effects of antipsychotic medication, social functioning, cognitive functioning, perceived health status, patient satisfaction, substance and alcohol use, sexual functioning and quality of life. The primary outcome will be remission of psychotic symptoms and no antipsychotic medication after 1 year. Secondary outcome measures will include: co-occurrence of remission of psychotic symptoms and 0–1-mg haloperidol equivalents of antipsychotic medication after 1-year intervention; antipsychotic dose; antipsychotic side effects; negative symptoms; social functioning; cognitive functioning; and patient satisfaction. Exploratory outcomes will include remission, clinical recovery, substance and alcohol use, sexual functioning, quality of life, self-beliefs of coping and user experience of support from health workers. Safety measures will include death, admissions to psychiatric hospital, severe self-harm and psychotic relapses.DiscussionThe TAILOR trial will contribute knowledge about the effect of tapering/discontinuation of antipsychotic medication in the early phases of schizophrenia and related disorders and the results may guide future clinical treatment regimens of antipsychotic treatment.Trial registrationEU Clinical Trials Register – EudraCT number: 2016-000565-23. Registered on 5 February 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2172-4) contains supplementary material, which is available to authorized users.

Medication discontinuation in first episode psychosis: thinking about the offset of psychotic disorders

“…The duration of these studies was limited, with three studies having follow-up for 1 year and the longest study lasting only 3 years. In contrast to Zipursky's findings, it has been estimated in a longitudinal cohort study that up to 40% of those who achieve remission after FEP may ultimately remain well without medication (Sturup et al, 2017).…”

“…The longitudinal design of the study will enable measurement of associations between antipsychotic medication and brain changes. A Danish RCT plans to compare maintenance treatment with closely monitored tapering/discontinuation of antipsychotic medication over 1 year, in people with newly diagnosed schizophrenia or persistent delusional disorder who have had 3 months remission of psychotic symptoms (Sturup et al, 2017). While these RCTs should be informative, in the meantime, we are faced with decisions about the optimal dose and duration of antipsychotic medication for people recovering from FEP.…”

Maintenance antipsychotic treatment versus discontinuation strategies following remission from first episode psychosis: systematic review

“…A benchmark of ten studies is often suggested for the conduct of a meta-regression, 38 however, numerous reviews have been conducted with fewer studies. 46 The problems associated with using a smaller number of studies are particularly related to multivariate meta-regression, 48 which we did not conduct in this study. There is a striking deficiency in the evidence base given how important the question of medication discontinuation after remission is to clinicians and patients.…”

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).…”