Agomelatine Use Research Articles

Effect of regulatory interventions on agomelatine use in Spain: A multiple intervention time-series analysis in a nationwide electronic healthcare record database.

Liver injury is an important identified risk for agomelatine and several measures were put in place to prevent and minimize such risk. The study aims to assess the impact of four interventions on the incidence of agomelatine use, particularly among patients aged ≥75 in Spain between 2011 and 2018. Quasi-experimental interrupted time-series analysis to examine data from a nationwide electronic healthcare record database (BIFAP). Quarterly cumulative incidence of agomelatine use per 100 000 patients was calculated and the impact of four regulatory interventions was quantified. The incidence of agomelatine use decreased by 85% and 87% from first quarter 2011 to last quarter 2018 in patients below and above 75 years old, respectively. Regulatory actions taken were not associated with an immediate and significant falling level of use or slope. The incidence was less than expected 6months after the first and third intervention for patients below and above 75 years old, and more than expected after the second and fourth intervention for both populations, though these analyses were underpowered to observe significant results. The downward trend became less pronounced, reaching a residual level of use, which remained stable in the last segment of the study period. New users of agomelatine decreased throughout the study period, starting before interventions took place. The effect of specific interventions might be masked by the progressive decrease tendency, constant over the study period. The effects of external factors that might overlap, unintended consequences, and issues concerning statistical modeling in situations where rates are already falling, should be considered when interpreting the results.

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

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.

Agomelatine, a novel therapeutic option for the management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a complex and chronic, relapsing gastrointestinal condition that affects more than 10% of the population worldwide. There is a pressing need for new therapeutic strategies in the management of IBS. Increasing research has shed light on the modulatory functions of melatonin on pain, local inflammation and motility in the gastrointestinal tract. However, melatonin's effects are limited by its extensive first-pass metabolism and short half-life. Agomelatine, a naphthalene analog of melatonin, is a novel melatonergic drug with a longer half-life and a comparatively greater affinity for MT1 and MT2 melatonin receptors than melatonin itself. Agomelatine also shows serotonin 5-HT3 receptor antagonist activity, which is theoretically of benefit for patients with IBS with diarrhoea (IBS-D) as it regulates gastrointestinal motility and visceral sensory mechanisms. Although only one clinical study of agomelatine use in patients with IBS exists, we believe that agomelatine is a safe and efficacious multimodal agent with untapped potential in the management of IBS. Numerous comorbidities are associated with IBS, including chronic pain syndromes and psychiatric disorders. Coupled with its antidepressant actions, agomelatine could serve as an effective adjunct therapeutic. Agomelatine should be considered in our therapeutic armamentarium for IBS management.

Agomelatine Use in Child and Adolescent Psychiatry

1Al-Manara CAP Centre, Kuwait Centre for Mental Health, Shuwaikh, Kuwait 2Al-Manara CAP Centre, Psychiatric Departments, Kuwait Centre for Mental Health, Shuwaikh, Kuwait 3Tufts University, Boston, MA 4Al-Ain University, Al-Ain, United Arab Emirates The authors have no conflicts of interest to declare.

Alopecia associated with agomelatine use: a case report

ABSTRACTDrug-induced alopecia, characterized by non-scarring hair loss of scalp and body, is a rare side effect of psychotropic drugs. It has previously been reported with the different antidepressant medications, but has not been described with agomelatine. Agomelatine is an antidepressant with a novel mechanism of action and fewer side effects. Here, we report a 31-year-old male patient with diffuse hair loss induced by agomelatine use and improved by discontinuation the drug. Because antidepressant-induced hair loss is relatively rare, many clinicians may not pay attention for this side effect. As far as we know, this is the first published case report of alopecia associated with agomelatine.

P.8.b.006 Side effects of zolpidem and temazepam in treating primary insomnia

There were no abnormalities in cardiovascular status. Baseline laboratory results again included a normal platelet count, normal liver enzymes and liver function tests. Hypomania was also excluded. After agomelatine discontinuation, symptoms improved. Adverse effect was determined by clinical pharmacist with the Naranjo probability scale and was probably associated with agomelatine use (6 points) and possibly associated with duloxetine hydrochloride use (4 points). After discussing the benefits and risks with the patient, a clinical pharmacist advised discontinuation of agomelatine and switching to trazodone 50mg daily at bedtime. The physician accepted our recommendations and the symptoms completely disappeared in three days after agomelatine discontinuation. Discussion: No case of agomelatine-induced sweating has been described. The interactions with agomelatine are reported to be mediated by cytochrome CYP1A2 enzymes. CYP1A2 and CYP2D6 have a major role in the metabolism of duloxetine hydrochloride and duloxetine hydrochloride increases the exposure of drugs that metabolized with CYP2D6, but not CYP1A2 [1]. Consequently any pharmacokinetics drug interaction between agomelatine and duloxetine hydrochloride had not occurred in this patient. An adverse effect was not induced by duloxetine hydrochloride itself, but pharmacodynamic drug–drug interaction between duloxetine hydrochloride and agomelatine could occur, which led to small additive adrenergic overstimulation. Such case has not yet been described in literature, however an adverse effect associated with drug–drug interaction can occur, as this report clearly demonstrates. No case of agomelatine-induced sweating has been described. Pharmacodynamic drug–drug interaction between agomelatine and duloxetine hydrochloride could occur, which led to small additive adrenergic overstimulation. Daily dose of duloxetine hydrochloride was not changed in switching time. This case serves to illustrate how clinical pharmacy can help ensure a satisfactory clinical outcome and prevent a potentially life threatening adverse drug reaction, similar to other case reports of timely recognition of adverse drug reactions from other psychotropic medications by clinical pharmacy that were followed by close collaboration between clinical pharmacy and psychiatry for successful management of the clinical disorder in question [2,3]. Conclusion: The benefit of this antidepressant combination needs to be carefully balanced with the risks associated with its use. Antidepressant combination treatment is common in some clinical practice settings, there is limited evidence to support this practice. Trazodone in small doses could be used in treating patients with agomelatine associated excessive sweating.

Hepatotoxicity Related to Agomelatine and Other New Antidepressants

Antidepressants have been associated with a low incidence of idiosyncratic hepatic injury. Some of them, nefazodone or amineptine, were observed to induce severe hepatic injury and withdrawn from the market. Recently, some cases of this severe condition have been reported in association with agomelatine use. Therefore, the objective of this study is to learn the risk of hepatic damage with agomelatine as compared with other new antidepressants. We took data from the Spanish, French, Italian, and Portuguese pharmacovigilance system databases. A case/noncase approach to assess the strength of the association between whichever antidepressant and hepatotoxicity was performed; cases were defined as reports of hepatotoxicity; noncases were reports of all reactions other than hepatotoxicity. Exposure was the recording of a new antidepressant in a report, whether or not it was suspected of causing the reaction. During the period surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants assessed. They represent 10.3% of all cases collected for these drugs; the corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of hepatotoxicity associated with agomelatine were collected since its introduction until the end of the period studied; they account for a percentage of 14.6. Agomelatine was statistically associated with hepatotoxicity in Spain [reporting odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4-9.7)], France (ROR, 2.4 [95% CI, 1.5-3.7]), and Italy (ROR, 5.1 [95% CI, 1.7-14.0]). Current results support the idea of agomelatine to be related to a higher hepatotoxicity risk. Physicians should consider early discontinuation if the condition is suspected; health authorities should promptly explore the best regulatory actions to be taken.

951 – Audit of the introduction of agomelatine in a district general hospital

Agomelatine is a novel antidepressant which was licensed in the United Kingdom in February 2009, but has not yet been included in national prescribing guidelines in the UK. The cost of Agomelatine and the need for monitoring of liver function during treatment have informed the development of strict local guidelines in respect of the initiation of Agomelatine. To assess the use of Agomelatine following introduction in a district general hospital outpatient setting. To determine whether Agomelatine use is in accordance with recently formulated local guidelines and to explore prescribing patterns for Agomelatine. Case notes were reviewed for consecutive patients prescribed Agomelatine over a 3 month study period. Using a specifically designed proforma, prescribing data, laboratory indices, outcome data and patient feedback were assessed against standards derived by consensus based on new prescribing guidelines. 27 patients were studied. Agomelatine was initiated in 93% of cases for major depressive disorder as third-line treatment. 89% of patients completed baseline liver function tests and 63% had these reviewed at all of 3 time-points as recommended. 14% did not require an increment to the 50mg dose. 33% discontinued Agomelatine. 44% experienced mild side-effects such as headaches and nausea. 56% did not require an additional anxiolytic and 14% were successfully discharged. Positive feedback was obtained verbally and with rating scales. Initiation of agomelatine in accordance with recommended standards proved possible in a district general hospital setting. Agomelatine was well tolerated and positive patient feedback was received.

Agomelatine Treatment of Major Depressive Disorder

To review the efficacy, safety, pharmacologic, and pharmacokinetic data of agomelatine to better understand its potential role in the treatment of patients with major depressive disorder. A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT(2C), MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder. All articles in English identified from the data sources were evaluated. Randomized, controlled trials involving humans were prioritized in the review. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. Agomelatine, a potent agonist at type 1 and 2 melatonin receptors, selectively inhibits serotonin. It is extensively metabolized via cytochrome P450 isoenyzmes 1A1, 1A2, and 2C9 to metabolites with less activity than the parent drug. Five randomized controlled studies were identified that examined the efficacy and safety of agomelatine in major depressive disorder. In general, agomelatine was found to produce significant improvements in depressive symptoms compared with placebo on many, but not all, rating scales. Three of the trials had active comparator arms (ie, venlafaxine, paroxetine). In these 3 investigations, agomelatine produced effects on depressive symptoms similar to those of the comparator drugs. A small number of studies have demonstrated sleep benefits with the use of agomelatine in depressed patients. Positive findings also exist for the use of agomelatine in seasonal affective disorder and bipolar depression. The most common adverse effects reported with agomelatine use were headache, nasopharyngitis, and gastrointestinal complaints. The magnitude of agomelatine-related adverse effects appears to be at least similar to some currently marketed antidepressants. Overall, agomelatine is a promising and well-tolerated medication for the treatment of major depressive disorder. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy and safety of agomelatine.