Pharmacotherapy for behavioural manifestations in frontotemporal dementia: An expert consensus from the European Reference Network for Rare Neurological Diseases (ERN-RND)

Casper Wittebrood; Marina Boban; Annchiara Cagnin; Sabina Capellari; François-Laurent De Winter; Atbin Djamshidian; Manuel Menéndez González; Lena E Hjermind; Lenka Krajcovicova; Johanna Krüger; Johannes Levin; Kathrin Reetz; Eloy Rodriguez Rodriguez; Jonathan Rohrer; Tim Van Langenhove; Carola Reinhard; Holm Graessner; Robert Rusina; Dario Saracino; Marion Houot; Harro Seelar; Rik Vandenberghe

doi:10.1111/ene.16446

Pharmacotherapy for behavioural manifestations in frontotemporal dementia: An expert consensus from the European Reference Network for Rare Neurological Diseases (ERN-RND)

Eur J Neurol. 2024 Oct 24:e16446. doi: 10.1111/ene.16446. Online ahead of print.

Authors

Casper Wittebrood¹, Marina Boban^{2

3}, Annchiara Cagnin⁴, Sabina Capellari^{5

6}, François-Laurent De Winter¹, Atbin Djamshidian⁷, Manuel Menéndez González^{8

9

10}, Lena E Hjermind¹¹, Lenka Krajcovicova¹², Johanna Krüger^{13

14

15}, Johannes Levin^{16

17

18}, Kathrin Reetz¹⁹, Eloy Rodriguez Rodriguez^{20

21

22}, Jonathan Rohrer²³, Tim Van Langenhove²⁴, Carola Reinhard²⁵, Holm Graessner^{26

27}, Robert Rusina²⁸, Dario Saracino^{29

30}, Marion Houot^{31

32

33}, Harro Seelar³⁴, Rik Vandenberghe¹

Affiliations

¹ Department of Neurology, University Hospital Leuven, Leuven, Belgium.
² Department of Cognitive Neurology, Referral Centre for Cognitive Neurology and Neurophysiology, University Hospital Centre Zagreb, Zagreb, Croatia.
³ School of Medicine, University of Zagreb, Zagreb, Croatia.
⁴ Department of Neuroscience and Padua Neuroscience Centre, University of Padua, Padua, Italy.
⁵ Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.
⁶ IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
⁷ Department of Neurology, Medical University Innsbruck, Innsbruck, Tyrol, Austria.
⁸ Department of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain.
⁹ Department of Medicine, Universidad de Oviedo, Oviedo, Spain.
¹⁰ Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.
¹¹ Department of Neuorology, Neurogenetics Clinic and Clinical Trial Unit, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
¹² First Department of Neurology, St Anne´s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
¹³ Department of Neurology, Neurocentre, Oulu University Hospital, Oulu, Finland.
¹⁴ Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
¹⁵ MRC, Oulu University Hospital, Oulu, Finland.
¹⁶ Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
¹⁷ German Centre for Neurodegenerative Diseases, Munich, Germany.
¹⁸ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁹ Department of Neurology, RWTH Aachen University, Aachen, Germany.
²⁰ Neurology Service, Marqués de Valdecilla University Hospital, Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain.
²¹ CIBERNED, Network Centre for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
²² Medicine and Psychiatry Department, University of Cantabria, Santander, Spain.
²³ Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK.
²⁴ Department of Neurology, Cognitive Centre, Ghent University Hospital, Ghent, Belgium.
²⁵ Centre for Rare Diseases and Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany.
²⁶ Institute for Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
²⁷ Centre for Rare Diseases, University Hospital Tübingen, Tübingen, Germany.
²⁸ Department of Neurology, Third Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic.
²⁹ Paris Brain Institute, Institut du Cerveau-ICM, Inserm U1127, CNRS UMR 7225, AP-HP-Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France.
³⁰ Reference Centre for Rare or Early Dementias, IM2A, Département de Neurologie, AP-HP-Hôpital Pitié-Salpêtrière, Paris, France.
³¹ Centre of Excellence of Neurodegenerative Disease (CoEN), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
³² Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
³³ Clinical Investigation Centre for Neurosciences, Institut du Cerveau (ICM), Pitié-Salpêtrière Hospital, Paris, France.
³⁴ Department of Neurology and Alzheimer Centre Erasmus MC, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

PMID: 39447217
DOI: 10.1111/ene.16446

Abstract

Background and purpose: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers.

Method: The study examined drug management decisions for several behavioural disturbances in patients with FTD by 21 experts across European expert centres affiliated with the European Reference Network for Rare Neurological Diseases (ERN-RND).

Results: The study revealed the highest consensus on drug treatments for physical and verbal aggression, impulsivity and obsessive delusions. Antipsychotics (primarily quetiapine) were recommended for behaviours posing safety risks to both patients and caregivers (aggression, self-injury and self-harm) and nightly unrest. Selective serotonin reuptake inhibitors were recommended for perseverative somatic complaints, rigidity of thought, hyperphagia, loss of empathy and for impulsivity. Trazodone was specifically recommended for motor unrest, mirtazapine for nightly unrest, and bupropion and methylphenidate for apathy. Additionally, bupropion was strongly advised against in 10 out of the 14 behavioural symptoms, emphasizing a clear recommendation against its use in the majority of cases.

Conclusions: The survey data can provide expert guidance that is helpful for healthcare professionals involved in the treatment of behavioural symptoms. Additionally, they offer insights that may inform prioritization and design of therapeutic studies, particularly for existing drugs targeting behavioural disturbances in FTD.

Keywords: drug therapy; expert testimony; frontotemporal dementia; neurobehavioural manifestations; neurodegenerative diseases.