Agomelatine safe, effective to treat adolescent MDD

Agomelatine proved safe and effective in treating adolescents with major depressive disorder who received psychosocial counseling, according to a double-blind randomized controlled phase 3 trial published in Lancet Psychiatry.

“Established recommendations and guidelines for treatment of moderate to severe depression in children and adolescents recommend initial treatment with cognitive behavioral therapy, interpersonal therapy, or a family-based therapy,” Celso Arango, MD, of the department of child and adolescent psychiatry at the Hospital General Universitario Gregorio Marañón in Madrid, Spain, and colleagues wrote. “Although psychotherapies are the preferred treatment for pediatric depression, they are not always easily available. Pharmacological treatments are thus a necessary alternative.”

The researchers added options to treat symptoms of major depressive disorder are few at this stage of development. Arango and colleagues sought to ascertain the short-term safety and efficacy of agomelatine in children and adolescents diagnosed with major depressive disorder.

The study was initiated as a 12-week trial in 46 specialist psychiatric units or centers across eight European countries and South Africa, including 396 participants aged 7 to 17 who were administered either 10 mg or 25 mg of agomelatine per day or placebo with an active control (10 mg to 20 mg of fluoxetine depending on symptom severity).

Standardized psychosocial counseling, which was specifically developed for the trial, was initiated from cohort selection and continued throughout the study, including the open-label extension. Outcomes were measured using standardized interviews at each study visit, and the primary endpoint was any alteration in Children's Depression Rating Scale–revised (CDRS-R) raw score from baseline to week 12.

Results showed positive outcomes with both dosages of agomelatine vs. placebo with a CDRS-R raw score of 4.22 (95% CI, 0.63–7.82) at 12 weeks, with a similar effect for fluoxetine. The overall effect was confirmed in adolescent participants but not in children. The drug produced no unexpected negative outcomes, including significant weight gain or effect on suicidal behavior, in either the child or adolescent groups.

“Agomelatine is noted for its relatively low rate of adverse events and manageable safety profile in the adult population,” Arango and colleagues wrote. “The safety data from this study indicate that agomelatine was well tolerated in the pediatric population.”