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- Title
Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression.
- Authors
Virtanen, Suvi; Lagerberg, Tyra; Takami Lageborn, Christine; Kuja-Halkola, Ralf; Brikell, Isabell; Matthews, Anthony A.; Lichtenstein, Paul; D'Onofrio, Brian M.; Landén, Mikael; Chang, Zheng
- Abstract
Key Points: Question: Do pediatric patients diagnosed with unipolar depression who receive antidepressant treatment have an increased incidence of mania/hypomania compared with patients not treated with antidepressants? Findings: In this cohort study including 43 677 children and adolescents diagnosed with unipolar depression, during a 12-week follow-up, patients treated with antidepressants did not have an increased incidence of mania/hypomania compared with patients who did not initiate antidepressant treatment. Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. Meaning: This study found no evidence of treatment-emergent mania/hypomania in children and adolescents with unipolar depression. Importance: Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. Objective: To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania. Design, Setting, and Participants: In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included. Exposures: The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days. Main Outcomes and Measures: Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline. Results: The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, −0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. Conclusion: This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention. This cohort study examines the risks for and incidence of mania episodes after 12 and 52 weeks in children and adolescents with unipolar depression who are prescribed antidepressants.
- Subjects
SWEDEN; MENTAL depression; DEPRESSION in adolescence; BIPOLAR disorder; ANTIDEPRESSANTS; CHILD patients; GIRLS; DEPRESSED persons
- Publication
JAMA Psychiatry, 2024, Vol 81, Issue 1, p25
- ISSN
2168-622X
- Publication type
Article
- DOI
10.1001/jamapsychiatry.2023.3555