Published: 27-09-2023 21:31 | Updated: 29-09-2023 09:04

Use of antidepressants and risk of manic episodes in children and adolescents

Mania is a possible but rare side effect of treatment with antidepressant medication in adults, but little has previously been known of this risk in depressed children and adolescents. A newly published paper in JAMA Psychiatry investigated this, finding no evidence of mania/hypomania induced by antidepressants by 12 weeks after treatment initiation. However, caution is necessary in treatment for children with more severe depression or where a parent has bipolar disorder.

Portrait of Suvi Virtanen
Suvi Virtanen, post doc at the Department of medical epidemiology and biostatistics, Karolinska Institutet Photo: Gunilla Sonnebring

What does the study show?

“In children and adolescents with unipolar depression, we did not find evidence of antidepressant-induced mania/hypomania by 12 weeks after treatment initiation. This corresponds to the timeframe for antidepressants to exert their psychotropic effect and when treatment-induced mania is expected to emerge. Hospitalizations, parental bipolar disorder, and the use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania”, says Suvi Virtanen, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics and first author of the paper.

Why are the results important?

Antidepressants are increasingly prescribed to pediatric patients with unipolar depression (as opposed to bipolar depression which is seldom diagnosed in childhood), but little is known about the risk of treatment-emergent mania (i.e., the transition from depression into mania shortly after the initiation of antidepressant treatment). Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. Our results provide complementary information to randomized clinical trials (RCTs) from a large cohort of patients treated in a real-world setting.

How did you perform the study?

We conducted a register-based study on children and adolescents, aged 4–17, diagnosed with unipolar depression between 2006 and 2019. We applied the emulation of target trial framework to guide the study design and analysis, which reduces bias in observational studies and brings the results as close as possible to what could be get from an RCT.

Zheng Chang
Zheng Chang, researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. Photo: Gunilla Sonnebring

What is the next step in your research?

"Antidepressant treatment was unrelated to the risk of mania/hypomania, suggesting other characteristics are more relevant when evaluating which patients may have an increased risk of switching from unipolar depression into mania. Our model using administrative information from several national registers had a moderate predictive ability, suggesting it is possible to identify patients at high risk for mania/hypomania with a prognostic clinical prediction model. The model has potential to be improved in later work”, says Zheng Chang, senior author of the paper and Principal Researcher at the Department of Medical Epidemiology and Biostatistics.

The study was done in collaboration with the Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University and was supported by funding from the Swedish Research Council (2018–02213) and the Swedish Research Council for Health, Working Life and Welfare (2022-00824).


Virtanen S, Lagerberg T, Takami Lageborn C, et al. Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression. JAMA Psychiatry. Published online September 27, 2023. doi:10.1001/jamapsychiatry.2023.3555