Suicidality in psychiatrically hospitalized children and adolescents: Demographics, treatment, and outcome.

BACKGROUND: Despite the high prevalence of suicidality in psychiatrically hospitalized youth, its risk factors and impact on inpatient psychopharmacologic treatment are unknown. We identified characteristics associated with suicidality in psychiatrically hospitalized youth and determined the association of suicidality with subsequent psychopharmacologic interventions. METHODS: Medical records from consecutive psychiatric admissions to a large, acute care, urban, pediatric hospital were analyzed retrospectively (N = 1,309). Demographic, clinical, and treatment-related features of suicidal and nonsuicidal youth were characterized. Logistic regression identified predictors of suicidality, and multiple comparison analyses evaluated the association between suicidality and changes to antidepressant prescribing during inpatient course. RESULTS: Compared with nonsuicidal patients, inpatients who were suicidal were more likely to have a mood disorder or posttraumatic stress disorder, as well as Cannabis and alcohol use, were more commonly girls, and at least 13 years of age (all P ≤ .05). Hospitalization was shorter for suicidal patients, was more likely to be associated with antidepressant treatment (P ≤ .001), and among suicidal patients prescribed antidepressants at the time of admission, was associated with a greater likelihood of changing antidepressant treatment compared with nonsuicidal inpatients (P ≤ .05). CONCLUSIONS: These findings reveal differences between suicidal and nonsuicidal psychiatrically hospitalized youth and suggest that suicidality is associated with specific pharmacologic treatment approaches within this population.

Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders. METHODS: A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships. RESULTS: Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021). CONCLUSIONS: Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size.

Assessment and treatment of anxiety disorders in children and adolescents.

Recent advances in the developmental epidemiology, neurobiology, and treatment of pediatric anxiety disorders have increased our understanding of these conditions and herald improved outcomes for affected children and adolescents. This article reviews the current epidemiology, longitudinal trajectory, and neurobiology of anxiety disorders in youth. Additionally, we summarize the current evidence for both psychotherapeutic and psychopharmacologic treatments of fear-based anxiety disorders (e.g., generalized, social, and separation anxiety disorders) in children and adolescents. Current data suggest that these disorders begin in childhood and adolescence, exhibit homotypic continuity, and increase the risk of secondary anxiety and mood disorders. Psychopharmacologic trials involving selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SSNRIs) are effective in pediatric patients with anxiety disorders and have generally demonstrated moderate effect sizes. Additionally, current data support cognitive behavioral therapy (CBT) for the treatment of these conditions in youth and suggest that the combination of psychotherapy + an SSRI may be associated with greater improvement than would be expected with either treatment as monotherapy.

Sexual abuse is associated with obese children and adolescents admitted for psychiatric hospitalization.

OBJECTIVE: To determine the relationship between a history of child abuse and obesity among children admitted for psychiatric hospitalization. STUDY DESIGN: The charts of 1434 youth consecutively admitted to an inpatient psychiatric facility during a 10-month period were retrospectively analyzed. Rates of physical and sexual abuse, as well as other factors believed to increase the risk of obesity, were compared between children whose body mass index (BMI) percentiles were between 5 and 80 and whose BMI percentiles were >85. RESULTS: After correcting for age, race, gender, and antipsychotic usage, we found that a reported history of sexual abuse was associated with increased probability of being overweight/obese (BMI percentile 85-99) compared with being of typical BMI (aOR 1.41). Reported physical abuse neither increased the risk of obesity nor moderated the association between sexual abuse and increased weight. Antipsychotic treatment and female gender also were associated with increased BMI percentiles, with antipsychotic usage being the only variable associated with increased risk of a BMI percentile >99. CONCLUSIONS: Among youth with significant psychiatric illness, a history of sexual abuse increases the risk of being overweight or obese, an association that warrants further study regarding the temporal relationship between sexual abuse and obesity and may inform future obesity prevention and intervention programs in children.

Neuroanatomic abnormalities in adolescents with generalized anxiety disorder: a voxel-based morphometry study.

BACKGROUND: Despite recent data implicating functional abnormalities in the neurocircuitry underlying emotional processing in pediatric anxiety disorders, little is known regarding neurostructural abnormalities within these systems. METHODS: Using voxel-based morphometry, gray and white matter volumes were compared in 15 medication-free adolescents with generalized anxiety disorder (GAD; and no comorbid major depressive disorder) and 28 age- and sex-matched healthy comparison subjects. RESULTS: Compared to healthy adolescents, youth with GAD had larger gray matter volumes in the right precuneus and right precentral gyrus and decreased gray matter volumes in the left orbital gyrus and posterior cingulate. White matter volumes were decreased in the left medial and superior frontal gyrus and were increased in the left inferior temporal gyrus in youth with GAD relative to healthy subjects. CONCLUSIONS: Adolescents with GAD, who are early in the course of their illness, exhibit abnormalities in neural structures that subserve threat appraisal, modulation of fear responses, attachment, and mentalization.

Establishing the neurobiologic basis of treatment in children and adolescents with generalized anxiety disorder.

Generalized anxiety disorder (GAD) is associated with significant morbidity in children and adolescents, yet only recently have the neuropharmacology and neurophysiology of this condition been studied in youth. Accumulating data suggest structural and functional abnormalities within the brain's fear networks in youth with GAD. Additionally, seven studies examined the efficacy of medications that modulate this system and, in some cases, the direct effects of these medications on structures within these networks (e.g. amygdala, ventrolateral prefrontal cortex [VLPFC]). In this review, we summarize the extant functional, functional connectivity, and structural neuroimaging data in children and adolescents with GAD. In addition, data concerning selective serotonin reuptake inhibitors (SSRIs), selective serotonin norepinephrine reuptake inhibitors (SSNRIs), atypical anxiolytics, benzodiazepines, and psychotherapy are reviewed in the context of the neurophysiology of pediatric GAD. The existing data suggest abnormal activity within the amygdala, VLPFC, and anterior cingulate cortex, as well as the possibility of impaired connectivity among these brain regions. In addition to numerous cognitive behavioral therapy (CBT) trials, five randomized, controlled psychopharmacologic trials primarily in youth with GAD suggest that SSRIs and SSNRIs are effective for this condition. These findings also raise the possibility that functional activity within the amygdala and VLPFC may be altered following successful treatment.

Pharmacogenomic Testing in Child and Adolescent Psychiatry: An Evidence-Based Review.

Significant advances have been made in the application of pharmacogenomic testing for the treatment of patients with psychiatric disorders. Over the past decade, a number of studies have evaluated the utility of pharmacogenomic testing in pediatric patients with psychiatric disorders. The evidence base for pharmacogenomic testing in youth with depressive and anxiety disorders as well as attention/deficit hyperactivity disorder (ADHD) is reviewed in this article. General pharmacogenomic principles are summarized and functional polymorphisms in P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter promoter polymorphisms, serotonin 2A receptor genes (e.g., HT2AR) and catecholamine pathway genes (e.g., COMT) are reviewed. These commonly tested pharmacogenomic markers are discussed with regard to studies of drug levels, efficacy and side effects. The translation of pharmacogenomics to individualized/precision medicine in pediatric patients with ADHD, anxiety and depressive disorders has accelerated; however, its application remains challenging given that there are numerous divergent pathways between medication/medication dose and clinical response and side effects. Nonetheless, by leveraging variations in individual genes that may be relevant to medication metabolism or medication target engagement, pharmacogenomic testing may have a role in predicting treatment response, side effects and medication selection in youth with ADHD, depressive and anxiety disorders.

Neurostructural impact of co-occurring anxiety in pediatric patients with major depressive disorder: a voxel-based morphometry study.

BACKGROUND: Depressive and anxiety disorders are among the most frequently occurring psychiatric conditions in children and adolescents and commonly present occur together. Co-occurring depression and anxiety is associated with increased functional impairment and suicidality compared to depression alone. Despite this, little is known regarding the neurostructural differences between anxiety disorders and major depressive disorder (MDD). Moreover, the neurophysiologic impact of the presence of anxiety in adolescents with MDD is unknown. METHODS: Using voxel-based morphometry, gray matter volumes were compared among adolescents with MDD (and no co-morbid anxiety disorders, n=14), adolescents with MDD and co-morbid anxiety ("anxious depression," n=12), and healthy comparison subjects (n=41). RESULTS: Patients with anxious depression exhibited decreased gray matter volumes in the dorsolateral prefrontal cortex (DLPFC) compared to patients with MDD alone. Compared to healthy subjects, adolescents with anxious depression had increased gray matter volumes in the pre- and post-central gyri. LIMITATIONS: The current sample size was small and precluded an analysis of multiple covariates which may influence GMV. CONCLUSIONS: Gray matter deficits in the DLPFC in youth with anxious depression compared to patients with MDD and no co-occurring anxiety may reflect the more severe psychopathology in these patients. Additionally, the distinct gray matter fingerprints of MDD and anxious depression (compared to healthy subjects) suggest differing neurophysiologic substrates for these conditions, though the etiology and longitudinal trajectory of the differences remain to be determined.

Hospitalized youth and child abuse: a systematic examination of psychiatric morbidity and clinical severity.

Many children and adolescents who require psychiatric hospitalization have been physically or sexually abused, yet the association between reported histories of abuse and the complexity and severity of mental illness among psychiatrically hospitalized youth is poorly described with regard to current inpatient psychiatric practice. We sought to determine the association between histories of abuse and psychiatric complexity and severity in psychiatrically hospitalized youth including comorbidity patterns, psychotropic medication use, reason for admission and length of hospitalization. A systematic chart review was performed on 1433 consecutive psychiatric hospitalizations of children and adolescents that occurred over a 10-month period. Children with a history of abuse were more likely to be diagnosed with multiple DSM-IV-TR disorders than non-traumatized children. A history of sexual abuse was associated with more medication use than in their non-traumatized peers and a higher likelihood of treatment with antipsychotic medications, both at admission and discharge. Physical and sexual abuse were independently associated with increased length of stays, with exposure to both physical and sexual abuse associated with a 2-day increase in duration of hospitalization compared to non-traumatized patients. The findings from this study draw attention to the adverse impact of abuse on psychiatric morbidity and complexity and suggest the need for trauma-informed treatment in psychiatric hospital settings.

Antipsychotic polypharmacy in children and adolescents at discharge from psychiatric hospitalization.

STUDY OBJECTIVE: Antipsychotic polypharmacy-the use of more than one antipsychotic concomitantly-has increased in children and adolescents and may be associated with increased adverse effects, nonadherence, and greater costs. Thus, we sought to examine the demographic and clinical characteristics of psychiatrically hospitalized children and adolescents who were prescribed antipsychotic polypharmacy and to identify predictors of this prescribing pattern. DESIGN: Retrospective medical record review. SETTING: The inpatient psychiatric unit of a large, acute care, urban children's hospital. PATIENTS: One thousand four hundred twenty-seven children and adolescents who were consecutively admitted and discharged between September 2010 and May 2011. MEASUREMENTS AND MAIN RESULTS: At discharge, 840 (58.9%) of the 1427 patients were prescribed one or more antipsychotics, and 99.3% of these received second-generation antipsychotics. Of these 840 patients, 724 (86.2%) were treated with antipsychotic monotherapy, and 116 (13.8%) were treated with antipsychotic polypharmacy. Positive correlations with antipsychotic polypharmacy were observed for placement or custody outside the biological family; a greater number of previous psychiatric admissions; longer hospitalizations; admission for violence/aggression or psychosis; and intellectual disability, psychotic, disruptive behavior, or developmental disorder diagnoses. Negative correlations with antipsychotic polypharmacy included admission for suicidal ideation/attempt or depression, and mood disorder diagnoses. Significant predictors of antipsychotic polypharmacy included admission for violence or aggression (odds ratio [OR] 2.76 [95% confidence interval (CI) 1.36-5.61]), greater number of previous admissions (OR 1.21 [95% CI 1.10-1.33]), and longer hospitalizations (OR 1.08 [95% CI 1.04-1.12]). In addition, diagnoses of intellectual disability (OR 2.62 [95% CI 1.52-4.52]), psychotic disorders (OR 5.60 [95% CI 2.29-13.68]), and developmental disorders (OR 3.18 [95% CI 1.78-5.65]) were predictors of antipsychotic polypharmacy. CONCLUSION: Certain youth may have a higher likelihood of being prescribed antipsychotic polypharmacy, which should prompt careful consideration of medication treatment options during inpatient hospitalization. Future examinations of the rationale for combining antipsychotics, along with the long-term safety, tolerability, and cost effectiveness of these therapies, in youth are urgently needed.

Cortical surface anatomy in pediatric patients with generalized anxiety disorder.

BACKGROUND: It is established that pediatric patients with generalized anxiety disorder (GAD) exhibit functional abnormalities and altered gray matter volumes in neural structures that subserve emotional processing, yet there are no data regarding the surface anatomy of the cerebral cortex in youth with GAD. METHODS: Using an automated surface-based approach (FreeSurfer), cortical thickness was assessed node-by-node over the entire cerebral cortex in adolescents with GAD and no co-occurring major depressive disorder (n=13) and healthy subjects (n=19). RESULTS: Compared with healthy adolescents, youth with GAD exhibited increased cortical thickness in the right inferolateral and ventromedial prefrontal cortex (i.e., inferior frontal gyrus), the left inferior and middle temporal cortex as well as the right lateral occipital cortex. No relationships were observed between cortical thickness and the severity of anxiety symptoms in the significant regions that were identified in the vertex-wise analysis. CONCLUSIONS: These findings suggest that, in adolescents with GAD, abnormalities in cortical thickness are present in an ensemble of regions responsible for fear learning, fear extinction, reflective functioning (e.g., mentalization), and regulation of the amygdala.