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Published in: Trials 1/2020

Open Access 01-12-2020 | Study protocol

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

Authors: Marieke J. H. Begemann, Ilse A. Thompson, Wim Veling, Shiral S. Gangadin, Chris N. W. Geraets, Erna van ‘t Hag, Sanne J. Müller-Kuperus, Priscilla P. Oomen, Alban E. Voppel, Mark van der Gaag, Martijn J. Kikkert, Jim Van Os, H. Filip E. Smit, Rikus H. Knegtering, Sybren Wiersma, Luyken H. Stouten, Harm J. Gijsman, Lex Wunderink, Anton B. P. Staring, Selene R. T. Veerman, Amrita G. S. Mahabir, Jörg Kurkamp, Gerdina H. M. Pijnenborg, Natalie D. Veen, Machteld Marcelis, Koen P. Grootens, Gunnar Faber, Nico J. van Beveren, Agaath Been, Truus van den Brink, Maarten Bak, Therese A. M. J. van Amelsvoort, Andrea Ruissen, Christine Blanke, Karin Groen, Lieuwe de Haan, Iris E. C. Sommer

Published in: Trials | Issue 1/2020

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Abstract

Background

Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition—a finding that was not replicated in another recently published long-term study.

Methods/design

The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3–6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years.

Discussion

The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse.

Trial status

Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026.

Trial registration

European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.
Appendix
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Metadata
Title
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
Authors
Marieke J. H. Begemann
Ilse A. Thompson
Wim Veling
Shiral S. Gangadin
Chris N. W. Geraets
Erna van ‘t Hag
Sanne J. Müller-Kuperus
Priscilla P. Oomen
Alban E. Voppel
Mark van der Gaag
Martijn J. Kikkert
Jim Van Os
H. Filip E. Smit
Rikus H. Knegtering
Sybren Wiersma
Luyken H. Stouten
Harm J. Gijsman
Lex Wunderink
Anton B. P. Staring
Selene R. T. Veerman
Amrita G. S. Mahabir
Jörg Kurkamp
Gerdina H. M. Pijnenborg
Natalie D. Veen
Machteld Marcelis
Koen P. Grootens
Gunnar Faber
Nico J. van Beveren
Agaath Been
Truus van den Brink
Maarten Bak
Therese A. M. J. van Amelsvoort
Andrea Ruissen
Christine Blanke
Karin Groen
Lieuwe de Haan
Iris E. C. Sommer
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3822-5

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