Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice

Abstract

Introduction Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The ‘Therapeutic Drug Monitoring (TDM)-VIGIL’ study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved (‘on-label’), and off-label use in clinical practice. Methods Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. Results 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4–10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). Conclusion Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Protective Effect of Schisandrin on CORT-Induced PC12 Depression Cell Model by Inhibiting Cell Apoptosis In Vitro

“…Up to now, depression has become the third largest burden disease in the world, and the number of suicides caused by depression has reached 1 million every year [ 3 ]. Conventional antidepressants, typically selective serotonin reuptake inhibitors (SSRIs), have limitations in long lag period, nonresponsive subpopulations, and adverse effects [ 4 – 6 ]. Therefore, it is of great significance to find new antidepressant drugs with more rapid, effective, economical, and safe antidepressant treatment.…”

Serious Adverse Drug Reactions to Antipsychotics in Minors with Multiple Disabilities: Preventability and Potential Cost Savings by Therapeutic Drug Monitoring

“…EPS and QTc prolongation were the most frequently observed sADRs. Interestingly, in the TDM Vigil study 25 , psychiatric (not somatic) sADRs were most frequently reported. In our sample, psychiatric sADRs were very rare.…”

Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry

“…The reference study for estimating the frequency of sADR was the TDM-VIGIL study with 8.3% sADR (Egberts et al 2022 ). An estimated sample size of 1600 electronic medical records of hospitalized patients was provided, with approximately half of the patients having at least 1 psychotropic medication documented during the inpatient stay.…”

“…Therefore, children and adolescents with mental disorders are at higher or unknown risk for serious adverse drug reactions (sADRs) (Gerlach and Warnke 2016 ). sADRs in children and adolescents treated with psychotropic drugs have been reported in clinical trials (Nor Aripin et al 2012 ) and everyday clinical practice (Aagaard et al 2010 ; Egberts et al 2022 ) and can have far-reaching consequences. There is an urgent need for a strict risk–benefit assessment and careful patient and drug monitoring (Egberts et al 2015 ).…”