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A systematic review of selective serotonin reuptake inhibitor (SSRI)-induced activation and manic/hypomanic switch in children and adolescents

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Scand J Child Adolesc Psychiatr Psychol. 2025 Dec 10;13(1):117-134. doi: 10.2478/sjcapp-2025-0011. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Serotonin selective reuptake inhibitor (SSRI) – induced activation and manic/hypomanic switch in children should be defined and delimited from each other. If not, this could contribute to inappropriate treatment decisions. This systematic review aimed, therefore, to explore how SSRI – induced activation and manic/hypomanic switch in children are defined, delimited from each other, assessed, and diagnosed.

METHODS: The PRISMA guidelines were followed. A systematic literature search was conducted in Pubmed, Cochrane, Scopus, and PsychINFO (from 8th to 15th March 2023). Eligible studies were in English, covering a population aged six to 18 years, where the outcome was activation or manic/hypomanic switch in relation to SSRI treatment. Two blinded assessors independently screened all abstracts, and thirty articles were included. Definitions, described symptoms, assessments, and inter-rater reliability were recorded.

RESULTS: Twelve articles were categorized as activation and 18 as mania/hypomania. Eight articles presented a clear definition of activation and four of mania/hypomania. Two articles presented inter-rater/test-retest reliability. One specific instrument was used for assessment of activation. No instrument was used for assessment of mania/hypomania. Symptom overlap was found, but more symptoms of ‘aggression and hostility’, ‘anxiety and panic’, and ‘suicide and self-harm’ were reported in activation while more ‘cognitive and thought process alterations’ and ‘changes in mood and emotions’ were reported in mania/hypomania.

DISCUSSION/CONCLUSION: Vague definitions, and inadequate assessments and diagnostic procedures were found. There were some differences in symptoms between activation and manic/hypomanic switch.

OTHER: The study protocol was published on Prospero 2023, CRD42023422133.

PMID:41404486 | PMC:PMC12704583 | DOI:10.2478/sjcapp-2025-0011

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