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

Anne Emilie Stürup, Heidi Dorthe Jensen, Signe Dolmer, Merete Birk, Nikolai Albert, Mai Nielsen, Carsten Hjorthøj, Lene Eplov, Bjørn H Ebdrup, Ole Mors, Merete Nordentoft, Anne Emilie Stürup, Heidi Dorthe Jensen, Signe Dolmer, Merete Birk, Nikolai Albert, Mai Nielsen, Carsten Hjorthøj, Lene Eplov, Bjørn H Ebdrup, Ole Mors, Merete Nordentoft

Abstract

Background: The 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 design: Two 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.

Discussion: The 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 registration: EU Clinical Trials Register - EudraCT number: 2016-000565-23 . Registered on 5 February 2016.

Keywords: Antipsychotic medication; Discontinuation; Early intervention; First-episode psychosis; Maintenance therapy; Minimal effective dose; Randomized clinical trial; Schizophrenia; Tapering.

Conflict of interest statement

Ethics approval and consent to participate

The trial has been approved by the Regional Research Ethics Committee in the Capital Region of Denmark on 8 September 2016 with file number H-16028814 and the amendment of 3 March 2017 with file number 57222. Informed consent will be collected by interview with the researcher (Additional files 2 and 3, depending on center). The patient will have time to consider and ask questions. The interview will be planned beforehand and take place in a room without other people except a possible assessor.

Any substantial changes in the protocol will be reported to the Regional Ethical Committee in the Capital Region of Denmark and the Danish Medicines Agency. A list of changes and amendments that is required to be reported can be found on the committee’s and the agency’s websites.

Consent for publication

Not applicable.

Competing interests

Dr. Ebdrup has received lecture fees from, and/or is part of, the Advisory Boards of Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia and Takeda Pharmaceutical Company. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of the TAILOR trial
Fig. 2
Fig. 2
The tapering/discontinuation intervention
Fig. 3
Fig. 3
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure

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