title: Agomelatine Improves Apathy in Frontotemporal Dementia.
abstract: Apathy is the most common initial symptom of frontotemporal dementia (FTD) and has been linked to frontal-subcortical dopaminergic system dysfunction. No pharmacological therapy has been approved for the treatment of apathy, but, on the basis of its physiopathological mechanism, we suspected that increasing prefrontal dopaminergic innervation could improve this disabling symptom.
  
  
  
  We evaluated a group of 24 nondepressed patients with a diagnosis of the behavioral variant of FTD, in order to determine the effectiveness on apathy of agomelatine, an antidepressant with MT1 and MT2 receptor agonism and 5-HT2C receptor antagonism; the latter leads to an increase in prefrontal dopaminergic and noradrenergic tone. To try to tease out the effects of 5-HT2C antagonism on apathy, patients were randomized, using a cross-over design, to receive either agomelatine 50 mg/day or sustained release melatonin 10 mg/day for 10 weeks in a double-blind procedure. At the end of the follow-up period, subjects receiving melatonin switched to agomelatine for the following 10 weeks.
  
  
  
  Agomelatine, but not melatonin, was associated with a significant reduction of apathy in FTD subjects and of caregiver distress due to patients' apathy. The switch from melatonin to agomelatine was associated with a reduction in apathetic behavior. Agomelatine was well-tolerated by all enrolled subjects.
  
  
  
  Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.
authors.affiliation: C. Mondino National Neurological Institute, and Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Callegari
authors.forename: Chiara
authors.initials: C
authors.lastname: Mattei
authors.forename: Francesca
authors.initials: F
authors.lastname: Benassi
authors.forename: Frank
authors.initials: F
authors.lastname: Krueger
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Yaldizli
authors.forename: Davide
authors.initials: D
authors.lastname: Sassos
authors.forename: Davide
authors.initials: D
authors.lastname: Massucco
authors.forename: Carlo
authors.initials: C
authors.lastname: Scialò
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.forename: Carlo
authors.initials: C
authors.lastname: Serrati
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cocito
authors.forename: Leonardo
authors.initials: L
authors.lastname: Emberti Gialloreti
authors.forename: Matteo
authors.initials: M
authors.lastname: Pardini
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D057565:Apathy / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000523:psychology*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D044123:Receptor, Melatonin, MT2 / Q000819:agonists; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D008550:Melatonin; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes