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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.

Zusammenfassung: Fragestellung: Diagnostische und klinische Faktoren sowie Behandlungsstrategien als prognostische Indikatoren für den Langzeitverlauf der Enkopresis im Kindes- und Jugendalter. Methodik: 85 Kinder und Jugendliche (Alter 9,6 ± 3,2 Jahre) mit Enkopresis (ICD 10 F98.1) wurden am Ende der stationären Behandlung und 35 von ihnen erneut nach einem Katamnesezeitraum von 5,5 ± 1,8 Jahren untersucht. Patienten mit geistiger Behinderung wurden ausgeschlossen. Die Therapie kombinierte stuhlregulierende und verhaltenstherapeutische Maßnahmen sowie eine Behandlung eventueller komorbider Achse-I-Störungen. Ergebnisse: Im stationären Verlauf kam es in 22% der Gesamtstichprobe zu völliger Symptomremission, in 8% bestand unveränderte Symptompersistenz. Bei den 35 Katamnesepatienten berichteten 40% Symptomfreiheit. Als signifikant entscheidend für den Erfolg stellten sich in der Nachuntersuchung Obstipationsfreiheit und die konsequente Therapie von psychiatrischen Begleiterkrankungen, v. a. des hyperkinetischen Syndroms, dar. Patienten mit einer Anpassungsstörung zeigten eine signifikant bessere Prognose als alle anderen Patienten. Diejenigen, die bereits zum Entlassungszeitpunkt symptomfrei waren, erwiesen auch in der Katamnese signifikant häufiger eine stabile Totalremission. Schlussfolgerungen: Die konsequente Behandlung einer Obstipation und die spezifische Therapie von psychiatrischen Begleiterkrankungen sind wichtige prognostische Faktoren der Enkopresis. Die stationäre Therapie führt signifikant häufiger zu langfristigem Erfolg, wenn erst bei Erlangung von Symptomfreiheit entlassen wird.

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.