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BACKGROUND Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n��=��78; mean age, 14.22������2.39; range, 7-18��years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.

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.

comparison of diagnostic, clinical and therapeutic features and their predictive value for the outcome of encopresis in children and adolescents.85 children and adolescents (aged 9.6 +/- 3.2 years) with severe encopresis (ICD 10: F98.1) were investigated during inpatient treatment and 35 of them again 5.5 +/- 1.8 years later. Mentally retarded patients were excluded. Inpatient therapy consisted of treating constipation and/or stool regulation by means of laxatives, behavioural approaches, and the specific therapy of comorbid psychiatric disorders.During inpatient treatment 22% of the patients experienced total remission, 8% an unchanged persistence of symptoms. Of the 35 patients studied at follow-up 5.5 years later, 40% were symptom-free. As main result, prognostic outcome depended significantly on sufficient treatment of obstipation. Another important factor was the specific therapeutic approach to psychiatric comorbidity, especially to ADHD. The outcome for patients with comorbid ICD 10: F43 was significantly better than for the other patients. Those who were symptom-free at discharge had significantly better long-term outcomes.Decisive to the success of encopresis treatment were the stool regulation and the specific therapy of associated psychiatric illnesses, in particular of ADHD. Inpatient treatment revealed significantly better long-term outcomes where total remission had been achieved by the time of discharge from hospital.