Citation

Begemann MJH, Thompson IA, Veling W, Gangadin SS, Geraets CNW, van 't Hag E, Müller-Kuperus SJ, Oomen PP, Voppel AE, van der Gaag M, Kikkert MJ, van Os J, Smit HFE, Knegtering RH, Wiersma S, Stouten LH, Gijsman HJ, Wunderink L, Staring ABP, Veerman SRT, Mahabir AGS, Kurkamp J, Pijnenborg GHM, Veen ND, Marcelis M, Grootens KP, Faber G, van Beveren NJ, Been A, van den Brink T, Bak M, van Amelsvoort TAMJ, Ruissen A, Blanke C, Groen K, de Haan L, Sommer IEC. Trials 2020; 21(1): e147.

Copyright

(Copyright © 2020, Holtzbrinck Springer Nature Publishing Group - BMC)

DOI

10.1186/s13063-019-3822-5

PMID

32033579

PMCID

PMC7006112

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.

Language: en

Keywords

Humans; Adult; Female; Male; Middle Aged; Adolescent; Severity of Illness Index; Practice Guidelines as Topic; Young Adult; Treatment Outcome; Treatment; Quality of Life; Follow-Up Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Psychotic Disorders; Antipsychotic Agents; Discontinuation; Maintenance; Randomized controlled trial; Pragmatic Clinical Trials as Topic; Single-Blind Method; Remission Induction; Multicenter Studies as Topic; Antipsychotic medication, first episode psychosis; Tapering, global functioning