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. 2025 Oct 17.
doi: 10.1038/s41380-025-03307-3. Online ahead of print.

Mental health trajectories of adolescents treated with psychotropic medications: insights from the european milestone study

Collaborators, Affiliations

Mental health trajectories of adolescents treated with psychotropic medications: insights from the european milestone study

Marta Magno et al. Mol Psychiatry. .

Abstract

The transition from Child and Adolescent (CAMHS) to Adult Mental Health Services (AMHS) can be challenging. Drawing on the sample of the European MILESTONE project, we explored changes in clinical profiles and treatment outcomes in adolescents transitioning to AMHS over two years, focusing on different pharmacological treatment patterns. The sample (N = 690; mean age: 17.7 years; SD = 0.29) was categorised into three groups based on medication patterns: continuous (Group 1), intermittent (Group 2), and never medicated (Group 3). Participants underwent four evaluations over two years using tools measuring psychopathology and functioning, including the Health of the Nation Outcome Scale for Child and Adolescents (HoNOSCA) and ASEBA Battery. We employed repeated-measures models to analyse clinical rating changes and a two-way mixed ANOVA to assess interaction between time and groups. Group 3 had significantly lower mean HoNOSCA ratings than Groups 1 and 2 (p < 0.001), indicating better mental health. By the last time point (T4), the factors associated with a reduced risk of severe illness included an improvement in the risk of suicide attempts (p = 0.038), enhanced everyday functional skills (p = 0.008), higher quality of life (p = 0.001), and being male (p = 0.020). The ASEBA Battery showed Group 1 had more internalising symptoms, while Group 2 had more externalising symptoms than Group 3. During the transition from CAMHS to AMHS, continuous medication was associated with higher symptom severity than intermittent or no pharmacological treatment. This may reflect either a more severe initial symptomatology requiring sustained pharmacotherapy or a medication-related paradox, whereby symptoms persist or intensify owing to treatment resistance or side effects. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics Approval: The study protocol (study registration numbers: ISRCTN83240263 and NCT03013595) was approved by the UK National Research Ethics Service Committee West Midlands, South Birmingham (15/WM/0052) and the ethical committee of the Italian coordinating site IRCCS Fatebenefratelli on 4.12.2014 (permission 70/2014). All procedures contributing to this study comply with the Helsinki Declaration of 1975, as revised in 2008.The project was approved by the local Ethics Committee on 4th December 2014 (opinion 70/2014). The authors affirm that all procedures involved in this work adhere to the ethical standards set by the appropriate national and institutional committees on human experimentation.

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