RETROSPECTIVELY ASSESSING THE EFFICACY OF AGOMELATINE IN BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

Abstract

Introduction Behavioral and psychologic symptoms of dementia (BPSD) are sources of increasing stress to patients and caregivers and escalate the cost of overall care for dementia cases. Moderate and severe BPSD often need medical treatment to improve symptoms. However, the use of antipsychotic medications or antidepressants often leads to side effects and increases disability. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effect on disturbed circadian rhythms and disrupted sleep–wake cycles. Its activity of 5HT-2C receptor antagonism is associated with antidepressant and antianxiety and increases slow-wave sleep. Agomelatine is also considered to be antioxidant and anti-inflammatory activity. It restores stress-affected hippocampal neuronal activity and promotes adult hippocampal neurogenesis and neuroplasticity. Previous clinical findings prompt that agomelatine can improve the BPSD of dementia patients. This retrospective cohort study was used to evaluate the BPSD of dementia cases before and after agomelatine use. Methods Dementia cases who ever received agomelatine treatment for depressive symptoms in a general hospital for past 2.5 years were fully reviewed. Their chart records, including the scores of Neuropsychiatric Inventory (NPI), were recorded. The changes of NPI score were used to evaluate the difference of psychological and behavioral symptoms before and after agomelatine use. The linear mixed-effect model is used to model the changes by controlling the confounding effects of age and sex, hypnotics, antipsychotic drugs, and the adjuvant drug –Mesyrel using. The side effects of agomelatine use were also invest. This study was approved by the institutional review board of National Cheng Kung University Hospital. Results There are 75 cases (male 26, female 49) with Alzheimer's Dementia (AD) 25, Dementia with Lewy Bodies (DLB) 21, Vascular Dementia (VaD) 15, Mixed type dementia 9, and other type dementia 5 cases having both NPI records, pre-and post-agomelatine use 3 months or more. The mean age is 80.7 years old. The dose of agomelatine is from 12.5mg to 50mg per day. The severity and distress of NPI records all show improvement after agomelatine use (p=0.001), especially in the items of delusion, hallucination, agitation/aggression, depression/dysphoria, anxiety, disinhibition, irritability/lability, motor disturbance, sleep/nighttime behavior disturbance (p Eight cases discontinued from agomelatine use due to side effects: 6 with headache, oversleep, dizziness; 1 ever had violence in the midnight, and 1 increased falling down risk in the night. The causes of switching from other antidepressants (such as sertraline, citalopram, escitalopram, paroxetine, venlafaxine, duloxetine, mirtazepine, bupropion, imipramine, doxeine or trazodone) to agomelatine were depression related symptoms not improved or the side effects of using these antidepressants. These side effects include psychomotor slowing, drowsiness or insomnia, dizziness, fatigue, weak, increasing extrapyramidal symptoms, loss of appetite, constipation, bruising or increasing skin itching. Conclusions Agomelatine is effective on improving behavioral and psychological symptoms of dementia, no matter in depression, sleep disturbance, delusion, hallucination, or aggression. The start low and go slow rule should be considered since side effects of headache, dizziness, sedation or triggering the fall. This research was funded by Agomelatine is effective on improving BPSD.