title: Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study.
abstract: Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy; Center for Communication and Neurorehabilitation Research-CNAPP, Rome, Italy. Electronic address: matteo.pardini@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Pardini
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cordano
authors.affiliation: Center for Communication and Neurorehabilitation Research-CNAPP, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benassi
authors.affiliation: Mental Health and Se.R.T. Department, National Health Service, Ancona, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Mattei
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Sassos
authors.affiliation: Psychiatric Inpatient Unit, Civil Hospital, Lavagna (GE), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Guida
authors.affiliation: Department of Neurology, IRCCS S. Martino Hospital-IST, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Serrati
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Primavera
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Amore
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cocito
authors.affiliation: Center for Communication and Neurorehabilitation Research-CNAPP, Rome, Italy; Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Emberti Gialloreti
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005221:Fatigue / Q000188:drug therapy* / Q000503:physiopathology; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008550:Melatonin / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists / 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; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes
keywords: Agomelatine; Dopamine; Fatigue; Melatonin; Noradrenaline