INTENSIFY-a randomized, controlled trial to investigate the effect of an early intensified pharmacological treatment for major psychiatric disorders after treatment failure in the current episode: a study protocol.

@article{okhuijsenpfeifer2026intensifya,
  title = {{INTENSIFY-a randomized, controlled trial to investigate the effect of an early intensified pharmacological treatment for major psychiatric disorders after treatment failure in the current episode: a study protocol.}},
  author = {Cynthia Okhuijsen-Pfeifer and Alessandro Serretti and Eduard Vieta and Lidia Ilzarbe and Chiara Fabbri and Oliver Howes and K. Oliver Schubert and Scott R. Clark and Dennis Liu and Alex Hofer and Simon Gasser and Alkomiet Hasan and Wolfgang Strube and Martin Driessen and Elilarasi Ratnalingam and Andreas Reif and Carmen Schiweck and Jan Engelmann and Susanne Englisch and Sarah E. Fromme and Rena S. Birner and Vivien J. Zobel and Mark Weiser and Revital Amiaz and Alessandra Minelli and Antonio Vita and Mirko Manchia and Pasquale Paribello and Armida Mucci and Paola Bucci and Paola Rocca and Claudio Brasso and Michael Craggs and Nikos Stefanis and Nikolaos Kokras and Ulrich Ebner-Priemer and Phillippe Fossati and Bianca Ueberberg and Hans-Jörg Assion and Hendrika H. van Hell and Peter M. van de Ven and Rutger M. van den Bor and Ruben P. van Boxel and Cynthia Okhuijsen-Pfeifer and Cynthia Okhuijsen-Pfeifer and Alessandro Serretti and Eduard Vieta and Lidia Ilzarbe and Chiara Fabbri and Oliver Howes and K. Oliver Schubert and Alex Hofer and Simon Gasser and Martin Driessen and Andreas Reif and Jan Engelmann and Sarah E. Fromme and Mark Weiser and Alessandra Minelli and Antonio Vita},
  journal = {Trials},
  year = {2026},
  month = aug,
  doi = {10.1186/s13063-026-09861-7},
  url = {https://europepmc.org/article/MED/42968118},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - INTENSIFY-a randomized, controlled trial to investigate the effect of an early intensified pharmacological treatment for major psychiatric disorders after treatment failure in the current episode: a study protocol.
AU  - Cynthia Okhuijsen-Pfeifer
AU  - Alessandro Serretti
AU  - Eduard Vieta
AU  - Lidia Ilzarbe
AU  - Chiara Fabbri
AU  - Oliver Howes
AU  - K. Oliver Schubert
AU  - Scott R. Clark
AU  - Dennis Liu
AU  - Alex Hofer
AU  - Simon Gasser
AU  - Alkomiet Hasan
AU  - Wolfgang Strube
AU  - Martin Driessen
AU  - Elilarasi Ratnalingam
AU  - Andreas Reif
AU  - Carmen Schiweck
AU  - Jan Engelmann
AU  - Susanne Englisch
AU  - Sarah E. Fromme
AU  - Rena S. Birner
AU  - Vivien J. Zobel
AU  - Mark Weiser
AU  - Revital Amiaz
AU  - Alessandra Minelli
AU  - Antonio Vita
AU  - Mirko Manchia
AU  - Pasquale Paribello
AU  - Armida Mucci
AU  - Paola Bucci
AU  - Paola Rocca
AU  - Claudio Brasso
AU  - Michael Craggs
AU  - Nikos Stefanis
AU  - Nikolaos Kokras
AU  - Ulrich Ebner-Priemer
AU  - Phillippe Fossati
AU  - Bianca Ueberberg
AU  - Hans-Jörg Assion
AU  - Hendrika H. van Hell
AU  - Peter M. van de Ven
AU  - Rutger M. van den Bor
AU  - Ruben P. van Boxel
AU  - Cynthia Okhuijsen-Pfeifer
AU  - Cynthia Okhuijsen-Pfeifer
AU  - Alessandro Serretti
AU  - Eduard Vieta
AU  - Lidia Ilzarbe
AU  - Chiara Fabbri
AU  - Oliver Howes
AU  - K. Oliver Schubert
AU  - Alex Hofer
AU  - Simon Gasser
AU  - Martin Driessen
AU  - Andreas Reif
AU  - Jan Engelmann
AU  - Sarah E. Fromme
AU  - Mark Weiser
AU  - Alessandra Minelli
AU  - Antonio Vita
PY  - 2026
DA  - 2026/08/05
JO  - Trials
DO  - 10.1186/s13063-026-09861-7
UR  - https://europepmc.org/article/MED/42968118
AB  - Background  Schizophrenia, bipolar depression and major depressive disorders collectively affect over 10 million people across the European Union and are associated with annual healthcare and societal costs of more than 600 billion euros. When diagnosed, patients are usually prescribed psychotropic medication. A substantial proportion of patients insufficiently responds to first- and second-line treatments, which is termed as treatment resistance. While third-line treatments are relatively effective in TR conditions, it remains unclear whether providing these treatments in an earlier phase provides benefits.Methods  INTENSIFY consists of three international, multicenter, controlled, randomized, open-label trials, with a treatment duration of 6 weeks. After failure of a first-line treatment in the current episode, 1254 participants will be recruited by at least 16 sites and randomized to either a third-line treatment (early intensified pharmacological treatment) or treatment as usual (standard second-line treatment). Adult participants (age ≥ 18yrs) with a diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder, major depressive disorder, or bipolar depression are eligible after a treatment failure in the current episode due to lack of efficacy. The primary objective is to compare change in symptom severity after 6 weeks. The secondary objective is to compare the two treatment arms on changes of severity symptoms, cognitive function, quality of life, functional measures, digital mental health markers, side effects and concomitant medication. ANCOVA analyses will be performed.Discussion  Should the current study show clinical evidence that the use of third-line treatment is efficacious and safe earlier to treat severe mental illness, the results could impact treatment guidelines in due course. In addition, the study will contribute to the identification of clinical, digital and blood-based markers that are associated with treatment response to early and intensified treatments.Trial registration  The trials are registered in www.Clinicaltrials  gov under numbers NCT05603104 (merged study protocol; study center in Israel) and under the numbers for the split protocols NCT05958875 (SZ), NCT05973786 (BD) and NCT05973851 (MDD) for the EU and UK sites. The study is registered in the Australian and New Zealand Clinical Trials Registry under Registration number ACTRN12625000327482 (SZ), ACTRN12625000328471 (BD) and ACTRN12625000329460 (MDD). Registered on April 17, 2025.
SN  - 1745-6215
ER  -