Callegari Ilaria, Mattei Chiara, Benassi Francesca, Krueger Frank, Grafman Jordan, Yaldizli Özgür, Sassos Davide, Massucco Davide, Scialò Carlo, Nobili Flavio, Serrati Carlo, Amore Mario, Cocito Leonardo, Emberti Gialloreti Leonardo, Pardini Matteo
C. Mondino National Neurological Institute, and Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy.
Neurodegener Dis. 2016;16(5-6):352-6. doi: 10.1159/000445873. Epub 2016 May 27.
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.
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.
背景/目的：淡漠是额颞叶痴呆（FTD）最常见的初始症状，且与额-皮质下多巴胺能系统功能障碍有关。目前尚无获批用于治疗淡漠的药物疗法，但基于其生理病理机制，我们推测增加前额叶多巴胺能神经支配可能改善这一致残症状。
我们评估了一组24例被诊断为行为变异型FTD的非抑郁患者，以确定阿戈美拉汀（一种具有MT1和MT2受体激动作用及5-HT2C受体拮抗作用的抗抑郁药；后者可导致前额叶多巴胺能和去甲肾上腺素能张力增加）对淡漠的疗效。为了试图厘清5-HT2C拮抗作用对淡漠的影响，采用交叉设计将患者随机分组，在双盲程序中接受50毫克/天阿戈美拉汀或10毫克/天缓释褪黑素治疗10周。在随访期结束时，接受褪黑素治疗的受试者在接下来的10周改用阿戈美拉汀。
阿戈美拉汀而非褪黑素与FTD受试者淡漠的显著减轻以及因患者淡漠导致的照料者痛苦减轻相关。从褪黑素改用阿戈美拉汀与淡漠行为的减少相关。所有入组受试者对阿戈美拉汀耐受性良好。
我们的数据尽管是初步的，但表明阿戈美拉汀可能是治疗FTD患者淡漠的一种新的有效方法。
