Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries
Major depressive disorder is a severe illness that frequently manifests before the age of 18 years, often recurring later in life. Paediatric medical treatment options are scarce. The melatonin receptor agonist and 5-hydroxytryptamine2C receptor antagonist agomelatine is used to treat adults, and co...
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| Veröffentlicht in: | The Lancet. Psychiatry 2022-02, Vol.9 (2), p.113-124 |
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| creator | Arango, Celso Buitelaar, Jan K Fegert, Jörg M Olivier, Valérie Pénélaud, Pierre-François Marx, Ute Chimits, Damien Falissard, Bruno Barylnik, Julia Birdeanu, Laura Bosch, Gert P Boychevskaya, Julia Boyev, Igor Bugán, Enikõ Bukhanovskaya, Olga Chaban, Oleg Dobrescu, Iuliana Feller, Gábor Flisiak-Antonijczuk, Halina Gácser, Magdolna Grigorieva, Elena Holttinen, Timo Ivanovic-Kovacevic, Svetlana Kapornai, Krisztina Kasimova, Lala Koren, Evgeniy Martsenkovsky, Igor Maruta, Nataliya O Matican, Mirela Matkovska, Tetiana Melnyk, Ellina Milovancevic, Milica Pejovic Mostova, Olha Nagy, Peter Nussbaum, Laura Petrov, Petar Pietraszczyk-Kedziora, Bozena Polnareva, Nadia Predescu, Elena Razsolkova, Vladislava Rybakowski, Filip Rymsha, Sofiia Schrönen, Juan P Shigashov, Dmitrii Skrypnikov, Andrii Stankovic, Miodrag Stevanovic, Dejan Timonen, Markku Väänänen, Juha-Matti van der Westhuizen, Jannie van Niekerk, Gert Venger, Olena Voloshchuk, Anatolii Wolañczyk, Tomasz |
| description | Major depressive disorder is a severe illness that frequently manifests before the age of 18 years, often recurring later in life. Paediatric medical treatment options are scarce. The melatonin receptor agonist and 5-hydroxytryptamine2C receptor antagonist agomelatine is used to treat adults, and could offer a new therapeutic option for paediatric patients. Therefore, we aimed to investigate the short-term antidepressant efficacy and safety of agomelatine in children and adolescents with major depressive disorder.
We performed a 12 week, randomised, double-blind, parallel-group, multicentre, phase 3 trial in 46 specialist psychiatric units or centres in Bulgaria, Finland, Hungary, Poland, Romania, Russia, Serbia, South Africa, and Ukraine. Participants (aged 7–17 years) were eligible if they were unresponsive to psychosocial therapy during the 3-week run-in period (Children's Depression Rating Scale–revised [CDRS-R] score of ≥45). Ethnicity was not recorded. We investigated short-term antidepressant efficacy of agomelatine (10 mg or 25 mg per day) versus placebo with an active control (fluoxetine 10–20 mg depending on symptom severity) after 12 weeks of treatment in children (aged 7–11 years) and adolescents (12–17 years) with major depressive disorder. Patients were randomly assigned (1:1:1:1) to agomelatine 10 mg, agomelatine 25 mg, placebo, or fluoxetine via an interactive response system with permuted-block randomisation. Standardised manualised psychosocial counselling, developed for this trial, was initiated from selection and continued throughout the study, including the open-label extension. All people involved in the conduct of the clinical trial and patients were masked to treatment allocation. Study outcomes were measured using standardised interviews at each study visit. The primary endpoint was change in CDRS-R raw score from baseline to week 12. This study is registered with EudraCT, 2015-002181-23.
Between Feb 23, 2016, and Jan 14, 2020, 466 individuals were assessed for eligibility and of 400 included patients, 396 (247 [62%] girls, 149 [38%] boys; mean age 13·7 years [SD 2·7]) were analysed (full analysis set). The primary objective was met; 25 mg/day agomelatine (n=94, with n=102 receiving 10 mg/day) resulted in an improvement versus placebo (n=101) in CDRS-R raw score of 4·22 (95% CI 0·63–7·82; p=0·040) at 12 weeks, with a similar effect for fluoxetine (n=99), establishing assay sensitivity. The overall effect was confirmed in adolescent |
| doi_str_mv | 10.1016/S2215-0366(21)00390-4 |
| format | Article |
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We performed a 12 week, randomised, double-blind, parallel-group, multicentre, phase 3 trial in 46 specialist psychiatric units or centres in Bulgaria, Finland, Hungary, Poland, Romania, Russia, Serbia, South Africa, and Ukraine. Participants (aged 7–17 years) were eligible if they were unresponsive to psychosocial therapy during the 3-week run-in period (Children's Depression Rating Scale–revised [CDRS-R] score of ≥45). Ethnicity was not recorded. We investigated short-term antidepressant efficacy of agomelatine (10 mg or 25 mg per day) versus placebo with an active control (fluoxetine 10–20 mg depending on symptom severity) after 12 weeks of treatment in children (aged 7–11 years) and adolescents (12–17 years) with major depressive disorder. Patients were randomly assigned (1:1:1:1) to agomelatine 10 mg, agomelatine 25 mg, placebo, or fluoxetine via an interactive response system with permuted-block randomisation. Standardised manualised psychosocial counselling, developed for this trial, was initiated from selection and continued throughout the study, including the open-label extension. All people involved in the conduct of the clinical trial and patients were masked to treatment allocation. Study outcomes were measured using standardised interviews at each study visit. The primary endpoint was change in CDRS-R raw score from baseline to week 12. This study is registered with EudraCT, 2015-002181-23.
Between Feb 23, 2016, and Jan 14, 2020, 466 individuals were assessed for eligibility and of 400 included patients, 396 (247 [62%] girls, 149 [38%] boys; mean age 13·7 years [SD 2·7]) were analysed (full analysis set). The primary objective was met; 25 mg/day agomelatine (n=94, with n=102 receiving 10 mg/day) resulted in an improvement versus placebo (n=101) in CDRS-R raw score of 4·22 (95% CI 0·63–7·82; p=0·040) at 12 weeks, with a similar effect for fluoxetine (n=99), establishing assay sensitivity. The overall effect was confirmed in adolescents (n=317), but not in children (n=79). No unexpected safety signals were observed with agomelatine, with no significant weight gain or effect on suicidal behaviours.
This first study in a paediatric population supports the efficacy of 25 mg/day agomelatine, in addition to psychosocial counselling, in treating adolescent patients with major depressive disorder, with no unexpected safety signals. This medication could provide another option in the limited psychopharmaceutical repertoire for management of major depressive disorder.
Servier.
[Display omitted]</description><identifier>ISSN: 2215-0366</identifier><identifier>EISSN: 2215-0374</identifier><identifier>DOI: 10.1016/S2215-0366(21)00390-4</identifier><identifier>PMID: 34919834</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acetamides - administration & dosage ; Acetamides - adverse effects ; Adolescent ; Child ; Counseling ; Depressive Disorder, Major - drug therapy ; Depressive Disorder, Major - therapy ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Humans ; Male ; Serotonin Receptor Agonists - administration & dosage ; Serotonin Receptor Agonists - adverse effects</subject><ispartof>The Lancet. Psychiatry, 2022-02, Vol.9 (2), p.113-124</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-d53c48dd49a505565363153a3932ca0b7bbad1a517de0fd73f1ccac2da706f503</citedby><cites>FETCH-LOGICAL-c365t-d53c48dd49a505565363153a3932ca0b7bbad1a517de0fd73f1ccac2da706f503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34919834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arango, Celso</creatorcontrib><creatorcontrib>Buitelaar, Jan K</creatorcontrib><creatorcontrib>Fegert, Jörg M</creatorcontrib><creatorcontrib>Olivier, Valérie</creatorcontrib><creatorcontrib>Pénélaud, Pierre-François</creatorcontrib><creatorcontrib>Marx, Ute</creatorcontrib><creatorcontrib>Chimits, Damien</creatorcontrib><creatorcontrib>Falissard, Bruno</creatorcontrib><creatorcontrib>Barylnik, Julia</creatorcontrib><creatorcontrib>Birdeanu, Laura</creatorcontrib><creatorcontrib>Bosch, Gert P</creatorcontrib><creatorcontrib>Boychevskaya, Julia</creatorcontrib><creatorcontrib>Boyev, Igor</creatorcontrib><creatorcontrib>Bugán, Enikõ</creatorcontrib><creatorcontrib>Bukhanovskaya, Olga</creatorcontrib><creatorcontrib>Chaban, Oleg</creatorcontrib><creatorcontrib>Dobrescu, Iuliana</creatorcontrib><creatorcontrib>Feller, Gábor</creatorcontrib><creatorcontrib>Flisiak-Antonijczuk, Halina</creatorcontrib><creatorcontrib>Gácser, Magdolna</creatorcontrib><creatorcontrib>Grigorieva, Elena</creatorcontrib><creatorcontrib>Holttinen, Timo</creatorcontrib><creatorcontrib>Ivanovic-Kovacevic, Svetlana</creatorcontrib><creatorcontrib>Kapornai, Krisztina</creatorcontrib><creatorcontrib>Kasimova, Lala</creatorcontrib><creatorcontrib>Koren, Evgeniy</creatorcontrib><creatorcontrib>Martsenkovsky, Igor</creatorcontrib><creatorcontrib>Maruta, Nataliya O</creatorcontrib><creatorcontrib>Matican, Mirela</creatorcontrib><creatorcontrib>Matkovska, Tetiana</creatorcontrib><creatorcontrib>Melnyk, Ellina</creatorcontrib><creatorcontrib>Milovancevic, Milica Pejovic</creatorcontrib><creatorcontrib>Mostova, Olha</creatorcontrib><creatorcontrib>Nagy, Peter</creatorcontrib><creatorcontrib>Nussbaum, Laura</creatorcontrib><creatorcontrib>Petrov, Petar</creatorcontrib><creatorcontrib>Pietraszczyk-Kedziora, Bozena</creatorcontrib><creatorcontrib>Polnareva, Nadia</creatorcontrib><creatorcontrib>Predescu, Elena</creatorcontrib><creatorcontrib>Razsolkova, Vladislava</creatorcontrib><creatorcontrib>Rybakowski, Filip</creatorcontrib><creatorcontrib>Rymsha, Sofiia</creatorcontrib><creatorcontrib>Schrönen, Juan P</creatorcontrib><creatorcontrib>Shigashov, Dmitrii</creatorcontrib><creatorcontrib>Skrypnikov, Andrii</creatorcontrib><creatorcontrib>Stankovic, Miodrag</creatorcontrib><creatorcontrib>Stevanovic, Dejan</creatorcontrib><creatorcontrib>Timonen, Markku</creatorcontrib><creatorcontrib>Väänänen, Juha-Matti</creatorcontrib><creatorcontrib>van der Westhuizen, Jannie</creatorcontrib><creatorcontrib>van Niekerk, Gert</creatorcontrib><creatorcontrib>Venger, Olena</creatorcontrib><creatorcontrib>Voloshchuk, Anatolii</creatorcontrib><creatorcontrib>Wolañczyk, Tomasz</creatorcontrib><creatorcontrib>study investigators</creatorcontrib><title>Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries</title><title>The Lancet. Psychiatry</title><addtitle>Lancet Psychiatry</addtitle><description>Major depressive disorder is a severe illness that frequently manifests before the age of 18 years, often recurring later in life. Paediatric medical treatment options are scarce. The melatonin receptor agonist and 5-hydroxytryptamine2C receptor antagonist agomelatine is used to treat adults, and could offer a new therapeutic option for paediatric patients. Therefore, we aimed to investigate the short-term antidepressant efficacy and safety of agomelatine in children and adolescents with major depressive disorder.
We performed a 12 week, randomised, double-blind, parallel-group, multicentre, phase 3 trial in 46 specialist psychiatric units or centres in Bulgaria, Finland, Hungary, Poland, Romania, Russia, Serbia, South Africa, and Ukraine. Participants (aged 7–17 years) were eligible if they were unresponsive to psychosocial therapy during the 3-week run-in period (Children's Depression Rating Scale–revised [CDRS-R] score of ≥45). Ethnicity was not recorded. We investigated short-term antidepressant efficacy of agomelatine (10 mg or 25 mg per day) versus placebo with an active control (fluoxetine 10–20 mg depending on symptom severity) after 12 weeks of treatment in children (aged 7–11 years) and adolescents (12–17 years) with major depressive disorder. Patients were randomly assigned (1:1:1:1) to agomelatine 10 mg, agomelatine 25 mg, placebo, or fluoxetine via an interactive response system with permuted-block randomisation. Standardised manualised psychosocial counselling, developed for this trial, was initiated from selection and continued throughout the study, including the open-label extension. All people involved in the conduct of the clinical trial and patients were masked to treatment allocation. Study outcomes were measured using standardised interviews at each study visit. The primary endpoint was change in CDRS-R raw score from baseline to week 12. This study is registered with EudraCT, 2015-002181-23.
Between Feb 23, 2016, and Jan 14, 2020, 466 individuals were assessed for eligibility and of 400 included patients, 396 (247 [62%] girls, 149 [38%] boys; mean age 13·7 years [SD 2·7]) were analysed (full analysis set). The primary objective was met; 25 mg/day agomelatine (n=94, with n=102 receiving 10 mg/day) resulted in an improvement versus placebo (n=101) in CDRS-R raw score of 4·22 (95% CI 0·63–7·82; p=0·040) at 12 weeks, with a similar effect for fluoxetine (n=99), establishing assay sensitivity. The overall effect was confirmed in adolescents (n=317), but not in children (n=79). No unexpected safety signals were observed with agomelatine, with no significant weight gain or effect on suicidal behaviours.
This first study in a paediatric population supports the efficacy of 25 mg/day agomelatine, in addition to psychosocial counselling, in treating adolescent patients with major depressive disorder, with no unexpected safety signals. This medication could provide another option in the limited psychopharmaceutical repertoire for management of major depressive disorder.
Servier.
[Display omitted]</description><subject>Acetamides - administration & dosage</subject><subject>Acetamides - adverse effects</subject><subject>Adolescent</subject><subject>Child</subject><subject>Counseling</subject><subject>Depressive Disorder, Major - drug therapy</subject><subject>Depressive Disorder, Major - therapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Serotonin Receptor Agonists - administration & dosage</subject><subject>Serotonin Receptor Agonists - adverse effects</subject><issn>2215-0366</issn><issn>2215-0374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQjRCIVqU_AeRjkQjYcew0XBCq-JIqcSicrYk96bpy7MWTLNqfyL_C2V16xRePx2_em5lXVS8Ffyu40O_umkaomkutrxrxmnPZ87p9Up2f0l379DHW-qy6JHrgnAvZctW1z6sz2faiv5btefXnDkac9wyiYziO3oLdszQyuE8TBph9ROYjsxsfXMZ4wIFLAclinIn99vOGTfCQMnO4zUjkd8icp5QdZpbRot_5eM-2tLebRMl6CMymJRKGUD7eM2AuLUPAeihv94blopEmT1him-KcUwhrvN0AIZNszitFaSquza1UJYP0ono2QiC8PN0X1c_Pn37cfK1vv3_5dvPxtrZSq7l2Str22rm2B8WV0kpqKZQE2cvGAh-6YQAnQInOIR9dJ0dhy1IaBx3Xo-Lyoro68m5z-rUgzab0asswEDEtZBothC6nlwWqjlCbE1HG0WyznyDvjeBmNdIcjDSrS6YR5mCkaUvdq5PEMkzoHqv-2VYAH44ALIPuPGZD1mO06HzZ-Gxc8v-R-AuaA7H8</recordid><startdate>202202</startdate><enddate>202202</enddate><creator>Arango, Celso</creator><creator>Buitelaar, Jan K</creator><creator>Fegert, Jörg M</creator><creator>Olivier, Valérie</creator><creator>Pénélaud, Pierre-François</creator><creator>Marx, Ute</creator><creator>Chimits, Damien</creator><creator>Falissard, Bruno</creator><creator>Barylnik, Julia</creator><creator>Birdeanu, Laura</creator><creator>Bosch, Gert P</creator><creator>Boychevskaya, Julia</creator><creator>Boyev, Igor</creator><creator>Bugán, Enikõ</creator><creator>Bukhanovskaya, Olga</creator><creator>Chaban, Oleg</creator><creator>Dobrescu, Iuliana</creator><creator>Feller, Gábor</creator><creator>Flisiak-Antonijczuk, Halina</creator><creator>Gácser, Magdolna</creator><creator>Grigorieva, Elena</creator><creator>Holttinen, Timo</creator><creator>Ivanovic-Kovacevic, Svetlana</creator><creator>Kapornai, Krisztina</creator><creator>Kasimova, Lala</creator><creator>Koren, Evgeniy</creator><creator>Martsenkovsky, Igor</creator><creator>Maruta, Nataliya O</creator><creator>Matican, Mirela</creator><creator>Matkovska, Tetiana</creator><creator>Melnyk, Ellina</creator><creator>Milovancevic, Milica Pejovic</creator><creator>Mostova, Olha</creator><creator>Nagy, Peter</creator><creator>Nussbaum, Laura</creator><creator>Petrov, Petar</creator><creator>Pietraszczyk-Kedziora, Bozena</creator><creator>Polnareva, Nadia</creator><creator>Predescu, Elena</creator><creator>Razsolkova, Vladislava</creator><creator>Rybakowski, Filip</creator><creator>Rymsha, Sofiia</creator><creator>Schrönen, Juan P</creator><creator>Shigashov, Dmitrii</creator><creator>Skrypnikov, Andrii</creator><creator>Stankovic, Miodrag</creator><creator>Stevanovic, Dejan</creator><creator>Timonen, Markku</creator><creator>Väänänen, Juha-Matti</creator><creator>van der Westhuizen, Jannie</creator><creator>van Niekerk, Gert</creator><creator>Venger, Olena</creator><creator>Voloshchuk, Anatolii</creator><creator>Wolañczyk, Tomasz</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202202</creationdate><title>Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries</title><author>Arango, Celso ; Buitelaar, Jan K ; Fegert, Jörg M ; Olivier, Valérie ; Pénélaud, Pierre-François ; Marx, Ute ; Chimits, Damien ; Falissard, Bruno ; Barylnik, Julia ; Birdeanu, Laura ; Bosch, Gert P ; Boychevskaya, Julia ; Boyev, Igor ; Bugán, Enikõ ; Bukhanovskaya, Olga ; Chaban, Oleg ; Dobrescu, Iuliana ; Feller, Gábor ; Flisiak-Antonijczuk, Halina ; Gácser, Magdolna ; Grigorieva, Elena ; Holttinen, Timo ; Ivanovic-Kovacevic, Svetlana ; Kapornai, Krisztina ; Kasimova, Lala ; Koren, Evgeniy ; Martsenkovsky, Igor ; Maruta, Nataliya O ; Matican, Mirela ; Matkovska, Tetiana ; Melnyk, Ellina ; Milovancevic, Milica Pejovic ; Mostova, Olha ; Nagy, Peter ; Nussbaum, Laura ; Petrov, Petar ; Pietraszczyk-Kedziora, Bozena ; Polnareva, Nadia ; Predescu, Elena ; Razsolkova, Vladislava ; Rybakowski, Filip ; Rymsha, Sofiia ; Schrönen, Juan P ; Shigashov, Dmitrii ; Skrypnikov, Andrii ; Stankovic, Miodrag ; Stevanovic, Dejan ; Timonen, Markku ; Väänänen, Juha-Matti ; van der Westhuizen, Jannie ; van Niekerk, Gert ; Venger, Olena ; Voloshchuk, Anatolii ; Wolañczyk, Tomasz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-d53c48dd49a505565363153a3932ca0b7bbad1a517de0fd73f1ccac2da706f503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acetamides - administration & dosage</topic><topic>Acetamides - adverse effects</topic><topic>Adolescent</topic><topic>Child</topic><topic>Counseling</topic><topic>Depressive Disorder, Major - drug therapy</topic><topic>Depressive Disorder, Major - therapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Serotonin Receptor Agonists - administration & dosage</topic><topic>Serotonin Receptor Agonists - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arango, Celso</creatorcontrib><creatorcontrib>Buitelaar, Jan K</creatorcontrib><creatorcontrib>Fegert, Jörg M</creatorcontrib><creatorcontrib>Olivier, Valérie</creatorcontrib><creatorcontrib>Pénélaud, Pierre-François</creatorcontrib><creatorcontrib>Marx, Ute</creatorcontrib><creatorcontrib>Chimits, Damien</creatorcontrib><creatorcontrib>Falissard, Bruno</creatorcontrib><creatorcontrib>Barylnik, Julia</creatorcontrib><creatorcontrib>Birdeanu, Laura</creatorcontrib><creatorcontrib>Bosch, Gert P</creatorcontrib><creatorcontrib>Boychevskaya, Julia</creatorcontrib><creatorcontrib>Boyev, Igor</creatorcontrib><creatorcontrib>Bugán, Enikõ</creatorcontrib><creatorcontrib>Bukhanovskaya, Olga</creatorcontrib><creatorcontrib>Chaban, Oleg</creatorcontrib><creatorcontrib>Dobrescu, Iuliana</creatorcontrib><creatorcontrib>Feller, Gábor</creatorcontrib><creatorcontrib>Flisiak-Antonijczuk, Halina</creatorcontrib><creatorcontrib>Gácser, Magdolna</creatorcontrib><creatorcontrib>Grigorieva, Elena</creatorcontrib><creatorcontrib>Holttinen, Timo</creatorcontrib><creatorcontrib>Ivanovic-Kovacevic, Svetlana</creatorcontrib><creatorcontrib>Kapornai, Krisztina</creatorcontrib><creatorcontrib>Kasimova, Lala</creatorcontrib><creatorcontrib>Koren, Evgeniy</creatorcontrib><creatorcontrib>Martsenkovsky, Igor</creatorcontrib><creatorcontrib>Maruta, Nataliya O</creatorcontrib><creatorcontrib>Matican, Mirela</creatorcontrib><creatorcontrib>Matkovska, Tetiana</creatorcontrib><creatorcontrib>Melnyk, Ellina</creatorcontrib><creatorcontrib>Milovancevic, Milica Pejovic</creatorcontrib><creatorcontrib>Mostova, Olha</creatorcontrib><creatorcontrib>Nagy, Peter</creatorcontrib><creatorcontrib>Nussbaum, Laura</creatorcontrib><creatorcontrib>Petrov, Petar</creatorcontrib><creatorcontrib>Pietraszczyk-Kedziora, Bozena</creatorcontrib><creatorcontrib>Polnareva, Nadia</creatorcontrib><creatorcontrib>Predescu, Elena</creatorcontrib><creatorcontrib>Razsolkova, Vladislava</creatorcontrib><creatorcontrib>Rybakowski, Filip</creatorcontrib><creatorcontrib>Rymsha, Sofiia</creatorcontrib><creatorcontrib>Schrönen, Juan P</creatorcontrib><creatorcontrib>Shigashov, Dmitrii</creatorcontrib><creatorcontrib>Skrypnikov, Andrii</creatorcontrib><creatorcontrib>Stankovic, Miodrag</creatorcontrib><creatorcontrib>Stevanovic, Dejan</creatorcontrib><creatorcontrib>Timonen, Markku</creatorcontrib><creatorcontrib>Väänänen, Juha-Matti</creatorcontrib><creatorcontrib>van der Westhuizen, Jannie</creatorcontrib><creatorcontrib>van Niekerk, Gert</creatorcontrib><creatorcontrib>Venger, Olena</creatorcontrib><creatorcontrib>Voloshchuk, Anatolii</creatorcontrib><creatorcontrib>Wolañczyk, Tomasz</creatorcontrib><creatorcontrib>study investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet. Psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arango, Celso</au><au>Buitelaar, Jan K</au><au>Fegert, Jörg M</au><au>Olivier, Valérie</au><au>Pénélaud, Pierre-François</au><au>Marx, Ute</au><au>Chimits, Damien</au><au>Falissard, Bruno</au><au>Barylnik, Julia</au><au>Birdeanu, Laura</au><au>Bosch, Gert P</au><au>Boychevskaya, Julia</au><au>Boyev, Igor</au><au>Bugán, Enikõ</au><au>Bukhanovskaya, Olga</au><au>Chaban, Oleg</au><au>Dobrescu, Iuliana</au><au>Feller, Gábor</au><au>Flisiak-Antonijczuk, Halina</au><au>Gácser, Magdolna</au><au>Grigorieva, Elena</au><au>Holttinen, Timo</au><au>Ivanovic-Kovacevic, Svetlana</au><au>Kapornai, Krisztina</au><au>Kasimova, Lala</au><au>Koren, Evgeniy</au><au>Martsenkovsky, Igor</au><au>Maruta, Nataliya O</au><au>Matican, Mirela</au><au>Matkovska, Tetiana</au><au>Melnyk, Ellina</au><au>Milovancevic, Milica Pejovic</au><au>Mostova, Olha</au><au>Nagy, Peter</au><au>Nussbaum, Laura</au><au>Petrov, Petar</au><au>Pietraszczyk-Kedziora, Bozena</au><au>Polnareva, Nadia</au><au>Predescu, Elena</au><au>Razsolkova, Vladislava</au><au>Rybakowski, Filip</au><au>Rymsha, Sofiia</au><au>Schrönen, Juan P</au><au>Shigashov, Dmitrii</au><au>Skrypnikov, Andrii</au><au>Stankovic, Miodrag</au><au>Stevanovic, Dejan</au><au>Timonen, Markku</au><au>Väänänen, Juha-Matti</au><au>van der Westhuizen, Jannie</au><au>van Niekerk, Gert</au><au>Venger, Olena</au><au>Voloshchuk, Anatolii</au><au>Wolañczyk, Tomasz</au><aucorp>study investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries</atitle><jtitle>The Lancet. Psychiatry</jtitle><addtitle>Lancet Psychiatry</addtitle><date>2022-02</date><risdate>2022</risdate><volume>9</volume><issue>2</issue><spage>113</spage><epage>124</epage><pages>113-124</pages><issn>2215-0366</issn><eissn>2215-0374</eissn><abstract>Major depressive disorder is a severe illness that frequently manifests before the age of 18 years, often recurring later in life. Paediatric medical treatment options are scarce. The melatonin receptor agonist and 5-hydroxytryptamine2C receptor antagonist agomelatine is used to treat adults, and could offer a new therapeutic option for paediatric patients. Therefore, we aimed to investigate the short-term antidepressant efficacy and safety of agomelatine in children and adolescents with major depressive disorder.
We performed a 12 week, randomised, double-blind, parallel-group, multicentre, phase 3 trial in 46 specialist psychiatric units or centres in Bulgaria, Finland, Hungary, Poland, Romania, Russia, Serbia, South Africa, and Ukraine. Participants (aged 7–17 years) were eligible if they were unresponsive to psychosocial therapy during the 3-week run-in period (Children's Depression Rating Scale–revised [CDRS-R] score of ≥45). Ethnicity was not recorded. We investigated short-term antidepressant efficacy of agomelatine (10 mg or 25 mg per day) versus placebo with an active control (fluoxetine 10–20 mg depending on symptom severity) after 12 weeks of treatment in children (aged 7–11 years) and adolescents (12–17 years) with major depressive disorder. Patients were randomly assigned (1:1:1:1) to agomelatine 10 mg, agomelatine 25 mg, placebo, or fluoxetine via an interactive response system with permuted-block randomisation. Standardised manualised psychosocial counselling, developed for this trial, was initiated from selection and continued throughout the study, including the open-label extension. All people involved in the conduct of the clinical trial and patients were masked to treatment allocation. Study outcomes were measured using standardised interviews at each study visit. The primary endpoint was change in CDRS-R raw score from baseline to week 12. This study is registered with EudraCT, 2015-002181-23.
Between Feb 23, 2016, and Jan 14, 2020, 466 individuals were assessed for eligibility and of 400 included patients, 396 (247 [62%] girls, 149 [38%] boys; mean age 13·7 years [SD 2·7]) were analysed (full analysis set). The primary objective was met; 25 mg/day agomelatine (n=94, with n=102 receiving 10 mg/day) resulted in an improvement versus placebo (n=101) in CDRS-R raw score of 4·22 (95% CI 0·63–7·82; p=0·040) at 12 weeks, with a similar effect for fluoxetine (n=99), establishing assay sensitivity. The overall effect was confirmed in adolescents (n=317), but not in children (n=79). No unexpected safety signals were observed with agomelatine, with no significant weight gain or effect on suicidal behaviours.
This first study in a paediatric population supports the efficacy of 25 mg/day agomelatine, in addition to psychosocial counselling, in treating adolescent patients with major depressive disorder, with no unexpected safety signals. This medication could provide another option in the limited psychopharmaceutical repertoire for management of major depressive disorder.
Servier.
[Display omitted]</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34919834</pmid><doi>10.1016/S2215-0366(21)00390-4</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2215-0366 |
| ispartof | The Lancet. Psychiatry, 2022-02, Vol.9 (2), p.113-124 |
| issn | 2215-0366 2215-0374 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2611666693 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Acetamides - administration & dosage Acetamides - adverse effects Adolescent Child Counseling Depressive Disorder, Major - drug therapy Depressive Disorder, Major - therapy Dose-Response Relationship, Drug Double-Blind Method Female Humans Male Serotonin Receptor Agonists - administration & dosage Serotonin Receptor Agonists - adverse effects |
| title | Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries |
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