Healy Colm, O'Hare Kirsite, Lång Ulla, Kerkelä Martta, Byrne Jonah, Veijola Juha, Pulakka Anna, Metsälä Johanna, Kajantie Eero, Kelleher Ian
Centre for Clinical Brain Sciences, Division of Psychiatry, https://ror.org/01nrxwf90University of Edinburgh, Edinburgh, UK.
School of Medicine, University College Dublin, Dublin, Ireland.
Eur Psychiatry. 2025 Jun 25;68(1):e82. doi: 10.1192/j.eurpsy.2025.10050.
Psychotic disorders are frequently preceded by depressive disorders, and it has been hypothesized that treatment of depression in youth may reduce risk for later psychosis. Using quasi-experimental methods, we estimated the causal relationship between the treatment of adolescent depression with selective serotonin reuptake inhibitors (SSRIs) and the risk of later psychosis.
We used data linkage from multiple national Finnish registries for all individuals ( = 697,289) born between 1987 and 1997 to identify depression diagnosed before age 18, cumulative SSRI treatment within three years of diagnosis, and diagnoses of non-affective psychotic disorders by end of follow-up (age 20-29). We used instrumental variable analyses, exploiting variability in prescribing across hospital districts to estimate causal effects. Analyses were conducted using two-stage least squares modelling. Sensitivity analyses examined effects stratified by confounders and effects of specific SSRIs.
Our final sample included 22,666 individuals diagnosed with depression in adolescence, of whom 60.2% ( = 13,650) had used SSRIs. 10.7% of adolescents with depression went on to be diagnosed with a non-affective psychotic disorder. SSRI treatment for adolescent depression was not associated with a reduced risk of developing a psychotic disorder (one-year 0.04,CI:-0.01 to 0.09; two-years 0.02,CI:-0.06 to 0.09; three-years -0.02,CI:-0.08 to 0.05).
Our quasi-experimental investigation does not support the hypothesis that treatment of adolescent depression reduces the subsequent risk of psychosis. Our findings question the assumption that treatment of common mental health disorders in youth may impact the risk of developing severe mental illnesses in adulthood.
精神病性障碍之前常伴有抑郁障碍，并且据推测，对青少年抑郁症的治疗可能会降低日后患精神病的风险。我们采用准实验方法，估计了选择性5-羟色胺再摄取抑制剂（SSRI）治疗青少年抑郁症与日后患精神病风险之间的因果关系。
我们利用芬兰多个国家登记处的数据链接，对1987年至1997年出生的所有个体（n = 697,289）进行分析，以确定18岁之前诊断出的抑郁症、诊断后三年内的累积SSRI治疗，以及随访结束时（20 - 29岁）的非情感性精神病性障碍诊断。我们采用工具变量分析，利用不同医院地区处方的差异来估计因果效应。分析采用两阶段最小二乘法建模。敏感性分析检验了按混杂因素分层的效应以及特定SSRI的效应。
我们的最终样本包括22,666名在青少年时期被诊断为抑郁症的个体，其中60.2%（n = 13,650）使用过SSRI。10.7%的青少年抑郁症患者后来被诊断为非情感性精神病性障碍。青少年抑郁症的SSRI治疗与患精神病性障碍风险降低无关（一年风险差0.04，95%置信区间：-0.01至0.09；两年风险差0.02，95%置信区间：-0.06至0.09；三年风险差 -0.02，95%置信区间：-0.08至0.05）。
我们的准实验研究不支持青少年抑郁症治疗可降低后续患精神病风险这一假设。我们的研究结果对青少年常见心理健康障碍的治疗可能会影响成年后患严重精神疾病风险这一假设提出了质疑。
