Pooled Analysis of Four Non-Interventional Studies: Effectiveness and Tolerability of the Antidepressant Agomelatine in Daily Practice

Laux, Gerd; Barthel, Bettina; Hajak, Göran; Lemke, Matthias R.; Volz, Hans-Peter

doi:10.1007/s12325-017-0485-z

Cited by 11 publications

(6 citation statements)

References 43 publications

(61 reference statements)

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“…For instance, agomelatine, licensed as an antidepressant in Europe and Australia, is a first-in-class melatonin agonist at MT1 and MT2 receptors, and a 5HT antagonist at 5-HT2b and 5-HT2c receptors. The antidepressant response to agomelatine has been found to be superior to placebo (2–4), and large open-label studies in clinical settings are supportive of agomelatine's utility (5, 6). However, the magnitude of mood changes following agomelatine intake has been questioned (7–10).…”

Section: Introductionmentioning

confidence: 99%

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

et al. 2018

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Background: Agomelatine is a melatonin agonist and 5HT antagonist developed for the treatment of major depressive disorder which also has some effects on the circadian system. Since circadian dysfunctions are thought to play a role in the pathophysiology of depression, some of the mechanism of action of this drug may relate to improvements in circadian rhythms.Objective: This proof of concept open-label study sought to determine if improvements in depressive symptoms following an adjunctive multimodal intervention including agomelatine intake are associated with the magnitude of circadian realignment. This was investigated in young people with depression, a subgroup known to have high rates of delayed circadian rhythms.Methods: Young people with depression received a psychoeducation session about sleep and circadian rhythms, were asked to progressively phase advance their wake up time, and completed an 8 weeks course of agomelatine (25–50 mg). Participants underwent semi-structured psychological assessments, ambulatory sleep-wake monitoring and measurement of melatonin circadian phase before and after the intervention.Results: Twenty-four young adults with depression (17–28 years old; 58% females) completed the study. After the intervention, depressive symptoms were significantly reduced [t(23) = 6.9, p < 0.001] and, on average, the timing of dim light melatonin onset (DLMO) shifted 3.6 h earlier [t(18) = 4.4, p < 0.001]. On average, sleep onset was phase shifted 28 min earlier [t(19) = 2.1, p = 0.047] and total sleep time increased by 24 min [t(19) = –2.6, p = 0.018]. There was no significant change in wake-up times. A strong correlation (r = 0.69, p = 0.001) was found between the relative improvements in depression severity and the degree of phase shift in DLMO.Conclusion: Although this needs to be replicated in larger randomized controlled trials, these findings suggest that the degree of antidepressant response to a multimodal intervention including psychoeducation and agomelatine intake may be associated with the degree of change in evening melatonin release in young people with depression. This offers promising avenues for targeted treatment based on the prior identification of objective individual characteristics.

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Section: Introductionmentioning

confidence: 99%

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

et al. 2018

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“…A predominant increase in transaminase activity reflects a disturbance in hepatocellular integrity. However, liver enzymes are neither sensitive nor specific for predicting the severity of hepatotoxicity [20,21] . Although the AST level in this patient was up to 30 times of the ULN, there were hardly any clinical manifestations.…”

Section: Discussionmentioning

confidence: 66%

CYP1A2 polymorphism may contribute to agomelatine-induced acute liver injury

Wang

et al. 2021

Medicine

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Rationale:Liver function monitoring is recommended when agomelatine is prescribed, although liver enzymes are not considered predictive biomarkers. Most patients present with acute liver injury, with only a few presenting with levels of liver enzymes that are over 30 times the upper limit of normal. The patient-specific risk factors that are associated with liver injury remain unclear. Thus, this report provides new insights into the mechanism of agomelatine-induced acute hepatocellular injury based on cytochrome P450 family 1 subfamily A member 2 (CYP1A2) polymorphism.Patient concerns:We present a case of acute hepatocellular injury in a 75-year-old man who was taking agomelatine at a dose of 50 mg/qn. All hepatitis virus test results were negative. No history of liver disease was observed. As CYP1A2 is the main metabolic enzyme of agomelatine, CYP1A2 AA (rs762551) genetic polymorphism was analyzed.Diagnosis:The patient's transaminases level exceeded the critical value on day 72 after starting oral agomelatine.Interventions:The patient received intravenous magnesium isoglycyrrhizinate, a liver cell-protecting agent, followed by the withdrawal of agomelatine.Outcomes:There was an improvement in the levels of the liver enzymes and no subsequent organ dysfunction was observed.Lessons:Here, we report a case of acute hepatocellular injury characterized by a very high aspartate aminotransferase level. Periodic liver function testing throughout the treatment period can help in the rapid and appropriate diagnosis of acute liver injury, particularly in the absence of typical clinical manifestations. Agomelatine hepatic toxicity might be related to an idiosyncratic metabolic reaction that depends on individual patient differences. As it is the main metabolic enzyme of agomelatine, CYP1A2 genetic polymorphism may contribute to liver injury by affecting its metabolites.

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“…According to a pooled analysis of 4 prospective, noninterventional studies, the incidence of acute hepatitis after agomelatine use was 0.5% [ 7 ]. Fulminant hepatic failure has been previously reported in a woman with fatty liver after taking agomelatine [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series

Chang

Chen

et al. 2021

Clin Psychopharmacol Neurosci

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Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

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Pooled Analysis of Four Non-Interventional Studies: Effectiveness and Tolerability of the Antidepressant Agomelatine in Daily Practice

Cited by 11 publications

References 43 publications

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

CYP1A2 polymorphism may contribute to agomelatine-induced acute liver injury

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series

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