Agomelatine improves apathy in frontotemporal dementia

Ilaria Callegari, Chiara Mattei, Francesca Benassi, Frank Krueger, Jordan Henry Grafman, Özgür Yaldizli, Davide Sassos, Davide Massucco, Carlo Scialò, Flavio Nobili, Carlo Serrati, Mario Amore, Leonardo Cocito, Leonardo Emberti Gialloreti, Matteo Pardini*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

Original languageEnglish (US)
Pages (from-to)352-356
Number of pages5
JournalNeurodegenerative Diseases
Volume16
Issue number5-6
DOIs
StatePublished - Sep 1 2016

Fingerprint

S 20098
Apathy
Frontotemporal Dementia
Melatonin
Melatonin MT1 Receptor
Melatonin MT2 Receptor
Receptor, Serotonin, 5-HT2C
Cross-Over Studies
Antidepressive Agents
Caregivers
Therapeutics
Pharmacology

Keywords

  • Apathy
  • Behavioral neurology
  • Dopamine
  • Frontotemporal dementia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Callegari, I., Mattei, C., Benassi, F., Krueger, F., Grafman, J. H., Yaldizli, Ö., ... Pardini, M. (2016). Agomelatine improves apathy in frontotemporal dementia. Neurodegenerative Diseases, 16(5-6), 352-356. https://doi.org/10.1159/000445873
Callegari, Ilaria ; Mattei, Chiara ; Benassi, Francesca ; Krueger, Frank ; Grafman, Jordan Henry ; Yaldizli, Özgür ; Sassos, Davide ; Massucco, Davide ; Scialò, Carlo ; Nobili, Flavio ; Serrati, Carlo ; Amore, Mario ; Cocito, Leonardo ; Emberti Gialloreti, Leonardo ; Pardini, Matteo. / Agomelatine improves apathy in frontotemporal dementia. In: Neurodegenerative Diseases. 2016 ; Vol. 16, No. 5-6. pp. 352-356.
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Callegari, I, Mattei, C, Benassi, F, Krueger, F, Grafman, JH, Yaldizli, Ö, Sassos, D, Massucco, D, Scialò, C, Nobili, F, Serrati, C, Amore, M, Cocito, L, Emberti Gialloreti, L & Pardini, M 2016, 'Agomelatine improves apathy in frontotemporal dementia', Neurodegenerative Diseases, vol. 16, no. 5-6, pp. 352-356. https://doi.org/10.1159/000445873

Agomelatine improves apathy in frontotemporal dementia. / Callegari, Ilaria; Mattei, Chiara; Benassi, Francesca; Krueger, Frank; Grafman, Jordan Henry; Yaldizli, Özgür; Sassos, Davide; Massucco, Davide; Scialò, Carlo; Nobili, Flavio; Serrati, Carlo; Amore, Mario; Cocito, Leonardo; Emberti Gialloreti, Leonardo; Pardini, Matteo.

In: Neurodegenerative Diseases, Vol. 16, No. 5-6, 01.09.2016, p. 352-356.

Research output: Contribution to journalArticle

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T1 - Agomelatine improves apathy in frontotemporal dementia

AU - Callegari, Ilaria

AU - Mattei, Chiara

AU - Benassi, Francesca

AU - Krueger, Frank

AU - Grafman, Jordan Henry

AU - Yaldizli, Özgür

AU - Sassos, Davide

AU - Massucco, Davide

AU - Scialò, Carlo

AU - Nobili, Flavio

AU - Serrati, Carlo

AU - Amore, Mario

AU - Cocito, Leonardo

AU - Emberti Gialloreti, Leonardo

AU - Pardini, Matteo

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background/Aims: 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. Methods: 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. Results: 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. Conclusions: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

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Callegari I, Mattei C, Benassi F, Krueger F, Grafman JH, Yaldizli Ö et al. Agomelatine improves apathy in frontotemporal dementia. Neurodegenerative Diseases. 2016 Sep 1;16(5-6):352-356. https://doi.org/10.1159/000445873