{"doi":"10.1007/s00787-024-02587-4","title":"Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study","abstract":"Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10 mg (n = 102), agomelatine 25 mg (n = 95), placebo (n = 103), and fluoxetine 10-20 mg (n = 100). After 12 weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25 mg for a further 92 weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25 mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25 mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25 mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7 years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104 weeks.Trial registration No: EUDRACT No. 2015-002181-23.","journal":"European Child & Adolescent Psychiatry","year":2024,"id":481757,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9373,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":506939,"name":"Jörg M. Fegert","orcid":"0000-0001-6070-4323","position":1,"is_corresponding":false},{"id":1321694,"name":"F. Picarel-Blanchot","orcid":"0000-0001-8232-0793","position":2,"is_corresponding":false},{"id":1321695,"name":"Ute C. Marx","orcid":"0000-0002-7077-9940","position":3,"is_corresponding":false},{"id":1322110,"name":"Lucie Truffaut-Chalet","orcid":null,"position":4,"is_corresponding":false},{"id":1322111,"name":"Pierre‐François Pénélaud","orcid":null,"position":5,"is_corresponding":false},{"id":109357,"name":"Jan K. Buitelaar","orcid":"0000-0001-8288-7757","position":6,"is_corresponding":false},{"id":1322112,"name":"the study investigators","orcid":null,"position":7,"is_corresponding":false},{"id":56339,"name":"Celso Arango","orcid":"0000-0003-3382-4754","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:07:10.067421Z","pmid":"39390266","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}