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
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
Affiliations
Marieke J. H. Begemann
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
Ilse A. Thompson
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
Wim Veling
Department of Psychiatry, University of Groningen, University Medical Center Groningen
Shiral S. Gangadin
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
Chris N. W. Geraets
Department of Psychiatry, University of Groningen, University Medical Center Groningen
Erna van ‘t Hag
Department of Psychiatry, University of Groningen, University Medical Center Groningen
Sanne J. Müller-Kuperus
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht
Priscilla P. Oomen
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
Alban E. Voppel
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
Mark van der Gaag
Parnassia Psychiatric Institute
Martijn J. Kikkert
Department of Research, Arkin Mental Health Care
Jim Van Os
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht
H. Filip E. Smit
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center
Rikus H. Knegtering
Lentis Research, Lentis Psychiatric Institute
Sybren Wiersma
Early Intervention Psychosis Team, GGZ inGeest Specialized Mental Health Care
Luyken H. Stouten
Centre for Early Psychosis, Parnassia Psychiatric Institute
Harm J. Gijsman
Program for Psychosis & Severe Mental Illness, Pro Persona Mental Health
Lex Wunderink
Department of Psychiatry, University of Groningen, University Medical Center Groningen
Anton B. P. Staring
Department ABC, Altrecht Psychiatric Institute
Selene R. T. Veerman
Community Mental Health, Mental Health Service Noord-Holland Noord
Amrita G. S. Mahabir
Early Psychosis Team, GGNet
Jörg Kurkamp
Center for Youth with Psychosis, Mediant ABC Twente
Gerdina H. M. Pijnenborg
Department of Psychotic Disorders, GGZ-Drenthe
Natalie D. Veen
GGZ Delfland, Delfland Institute for Mental Health Care
Machteld Marcelis
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center
Koen P. Grootens
Reinier van Arkel Institute for Mental Health Care
Gunnar Faber
Yulius, Mental Health Institute
Nico J. van Beveren
Antes Center for Mental Health Care
Agaath Been
Center for Developmental Disorders, Dimence Institute for Mental Health
Truus van den Brink
Early Intervention Team, GGZ Centraal
Maarten Bak
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center
Therese A. M. J. van Amelsvoort
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, EURON, Maastricht University Medical Center
Andrea Ruissen
Emergis, Kenniscentrum
Christine Blanke
Anoiksis, University Medical Center Utrecht
Karin Groen
MIND Ypsilon, Organization of Relatives and Carers of People with a Vulnerability to Psychosis
Lieuwe de Haan
Department of Early Psychosis, Amsterdam UMC, Academic Medical Center
Iris E. C. Sommer
Department of Biomedical Sciences of Cells & Systems, Cognitive Neurosciences, University of Groningen, University Medical Center Groningen (UMCG)
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.