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

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

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial (“TDM-VIGIL”), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7–18 years; 24.6% males) was treated with fluoxetine (10–40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208–328 ng/mL (transdiagnostically) and 201.5–306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose–serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults

Is it adaptive to disengage from demands of social change? Adjustment to developmental barriers in opportunity-deprived regions

This paper investigates how individuals deal with demands of social and economic change in the domains of work and family when opportunities for their mastery are unfavorable. Theoretical considerations and empirical research suggest that with unattainable goals and unmanageable demands motivational disengagement and self-protective cognitions bring about superior outcomes than continued goal striving. Building on research on developmental deadlines, this paper introduces the concept of developmental barriers to address socioeconomic conditions of severely constrained opportunities in certain geographical regions. Mixed-effects methods were used to model cross-level interactions between individual-level compensatory secondary control and regional-level opportunity structures in terms of social indicators for the economic prosperity and family friendliness. Results showed that disengagement was positively associated with general life satisfaction in regions that were economically devastated and has less than average services for families. In regions that were economically well off and family-friendly, the association was negative. Similar results were found for self-protection concerning domain-specific satisfaction with life. These findings suggest that compensatory secondary control can be an adaptive way of mastering a demand when primary control is not possible

Psychosocial adaptation of adolescent migrants in a Swiss community survey

OBJECTIVE: The aim of this study was to compare psychosocial adaptation in adolescent (first generation) migrants, double-citizens (mainly second generation with one migrant parent), and native Swiss, and to compare migrants from various European regions. METHOD: Data from a community survey were based on 1,239 participants (mean age 13.8, SD = 1.6 years) with 996 natives, 55 double-citizens, and 188 migrants. The adolescents completed the youth self-report measuring emotional and behavioural problems, and various questionnaires addressing life events, personality variables, perceived parental behaviour (PPB), family functioning, school environment, and social network. RESULTS: Adolescent migrants had significantly higher scores for internalizing and externalizing problems. There was a pattern of various unfavourable psychosocial features including life events, coping, self-related cognitions, and PPB that was more common among adolescent migrants than natives. Double-citizens were similar to natives in all domains. Young adolescents from South and South-East Europe differed from natives in terms of more unfavourable psychosocial features. Migrant status was best predicted by adverse psychosocial features rather than emotional and behavioural problems. CONCLUSION: There is some indication that certain migrant adolescents are at risk of psychosocial mal-adaptation. Obviously, ethnic origin is an important moderator

Die kinder- und jugendpsychiatrische Klientel im Kanton Zürich über zwei Jahrzehnte

Data reflecting the clientele of the Child and Adolescent Psychiatric Service of the Canton of Zurich (Switzerland) spanning two decades between 1973 and 1993 were analyzed. Referral patterns, age distribution, sex ratio in relation to age, and family background are reported on. In addition, the distributions of diagnoses according to ICD-9 and ICD-10, respectively, are compared. Furthermore, four main types of child and adolescent psychiatric disorders are documented with regard to age distribution. Finally, abnormal psychosocial situations according to the multiaxial scheme of classification are reported

A Follow-Up Study of Child Psychiatric Clinic Attenders with Minor Neurological Dysfunction

Thirty-two child psychiatric patients with minor neurological dysfunction (MND) were followed-up after a mean interval of 5.3 years. Six clusters were analyzed that measured posture and muscle tonus, reflexes, coordination and balance, fine manipulative ability, choreiform dyskinesia, and associated movements. In the majority of cases, remission occurred for posture and muscle tonus, and choreiform dyskinesia and reflexes. Problems with fine manipulative ability and associated movements, however, persisted in most cases. Change in the total MND-abnormality score was also analyzed. Elevated scores and greater age at the initial assessment, and longer intervals between the initial assessment and follow-up were associated with greater improvement, indicating that biological maturation is an important factor in symptom remission. Slow background activity was the predominant EEG-pattern that tended to persist rather than to remit over time. A wide spectrum of psychiatric diagnoses was recorded on both occasions. In general, the tendency for remission of psychiatric disorders was stronger than that of persistence and new manifestation. In addition, with regard to behavioural abnormalities, the total score and subscore for emotional disorders diminished over time