Short summary

This study is a part of a large multinational study assessing the risk of acute liver injury in users of agomelatine and other antidepressant agents. Due to the expected low validity of the diagnosis in the Danish National Patient Registry compatible with acute liver injury, all cases of acute liver injury included in the study will be validated through medical record abstraction.

Rationale

Agomelatine is a melatonergic agonist and 5-HT2C antagonist indicated for major depressive episodes in adults. The marketing authorisation was granted in the European Union in February 2009 and renewed in November 2013. Agomelatine is covered by a European risk management plan that includes hepatotoxic reactions as an identified important risk. To completely characterise the hepatic risk with agomelatine, the European risk management plan included as an additional pharmacovigilance activity a post-authorisation safety study assessing and investigating this risk in current medical practice in patients newly treated with agomelatine and major antidepressants.

All previous studies highlight the need for validation by medical record review when conducting studies of acute liver injury in automated health care data sources. This is especially important in drug safety studies in which relying only on algorithms for automated case identification will most likely result in misclassification and overestimation of the true incidence of acute liver injury and biased effect estimates.

Description of the cohort

Our study population consists of patients who have:

1. filled at least one prescription of an antidepressant agent in the period 2009-2014
   AND
2. been registered with a code compatible with acute liver injury in the Patient Registry afterwards
   AND
3. no prior history of liver disease    

Data and biological material

From registries: medical history

From medical records: medical history and laboratory values.

Collaborating researchers and departments

Department of Clinical Pharmacology, Odense University Hospital

• Professor Jesper Hallas
• Associate professor Anton Pottegård, MSc.Pharm, PhD
• PhD-student Maja Hellfritzsch Poulsen, MD

RTI Health Solution, Barcelona

• Director of Epidemiolog, Manel Pladevall-Vila, MD, MS
• Head of Epidemiology Susana Perez-Gutthann, MD, PhD