Familial pathways to suicidal behavior--understanding and preventing suicide among adolescents.
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Adolescent↗
Biomedical subjects
David A Brent
Publications and source records attributed to David A Brent.
Effectiveness of cognitive-behavioral therapy for adolescent depression: a benchmarking investigation.
In this study, we examined the effectiveness of cognitive-behavioral therapy (CBT) for adolescent depression. Outcomes of 80 youth treated with CBT in an outpatient depression specialty clinic, the Services for Teens at Risk Center (STAR), were compared to a "gold standard" CBT research benchmark. On average, youths treated with CBT in STAR experienced significantly slower symptom improvement than youths in the CBT benchmark. However, outcomes for STAR teens were more similar to the research benchmark when accounting for differences in referral source (clinical versus advertisement) between the datasets. Results support further efforts to test the effectiveness of CBT in clinically representative community practice settings and samples.
Adult↗
Screens and doors: the management of adolescent depression in primary care.
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Adolescent↗
Treatment-resistant depression in adolescents: recognition and management.
Approximately 20% of adolescents experience at least one depressive episode by the time they enter their adult years. For most adolescents, depression, although serious, either remits spontaneously or responds to treatment. For a smaller but significant proportion of adolescents, however, depression can be long-lasting and relatively unresponsive to initial treatment. In this article the authors provide an operational definition of treatment-resistant depression, identify factors associated with treatment nonresponse, describe an approach to the management of treatment-resistant depression, and advance suggestions for promising avenues of research.
Adolescent↗
Depressive disorders in childhood and adolescence: an overview: epidemiology, clinical manifestation and risk factors.
The diagnostic category of depressive disorder in pediatric age is a relatively new concept that is rooted in empirical studies that date back to only the late 1980s. This article discusses the current consensus nosology and epidemiology of unipolar depressive disorders in young age and the risk factors for depression onset and recurrence. There is also a brief overview of psychosocial and pharmacologic evidence-based therapies and suggested areas for future research. This article also contains a brief description of the items discussed in detail in this issue.
Adolescent↗
Cognitive behavioral therapy for depression in youth.
Without question, cognitive behavioral therapy (CBT) is the most studied non-pharmacological intervention for the treatment of depression in youth, with over 80% of published psychotherapy trials testing the effects of CBT protocols. Until quite recently, CBT also was widely proclaimed to be a highly effective intervention for youth depression, albeit with stronger data for adolescent than for child samples. However, within the past two years, a series of new findings have complicated this previously rosy picture of CBT. The most well-known results come from the Treatment of Adolescents with Depression Study (TADS, 2004). In the TADS investigation, CBT failed to outperform a pill placebo, while active medication treatments (fluoxetine alone and fluoxetine-plus-CBT) produced strong and consistent effects. In this article, the authors strive to make sense of these seemingly conflicting findings, provide direction for the appropriate use of CBT in practice given the current evidence base, and suggest areas of additional investigation that may help to clarify the current confusion on the effects of CBT.
Adaptation, Psychological↗
Steady-state clinical pharmacokinetics of bupropion extended-release in youths.
OBJECTIVE: To examine in children and adolescents the 24-hour, steady-state clinical pharmacokinetics of an extended-release (XL) formulation of bupropion (Wellbutrin XL). METHOD: Subjects were six male and four female patients (ages 11.5-16.2 years) prescribed bupropion XL in morning daily doses of either 150 mg (n = 5) or 300 mg (n = 5) for at least 14 days. During an overnight hospitalization, subjects had serial blood draws every 1.5 to 3 hours from an intravenous port to measure plasma levels of bupropion and its metabolites. Pharmacokinetic variables were determined by noncompartmental analysis for bupropion and exponential analyses for metabolites. RESULTS: Bupropion and metabolites demonstrated linear pharmacokinetics. Bupropion's mean maximum concentration (Cmax) was lower (p = .021) and its mean time to Cmax longer (p = .057) in the current sample on bupropion XL relative to a previously studied sample of youths on bupropion sustained-release (Wellbutrin SR). Mean 24-hour area under the curve ratios of metabolites to bupropion ranged from 1.0 for erythrohydrobupropion to 16.4 for hydroxybupropion. CONCLUSIONS: Once-daily dosing is justified in youths prescribed bupropion XL. The active metabolite hydroxybupropion probably has key pharmacodynamic effects, given its higher and more sustained levels relative to the other metabolites or to bupropion.
Adolescent↗
Glad for what TADS adds, but many TADS grads still sad.
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Adolescent↗
Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study.
Studies examining associations between antidepressant response and plasma levels of bupropion and its metabolites have yielded contradictory findings. There have been no such studies in youth. This study explored such associations in 8 boys and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (SR) for major depression (n = 6) or depressive disorder not otherwise specified (n = 10) as part of a pharmacokinetic (PK) study. All were started on morning doses of bupropion SR of 100 mg/day, and most eventually had doses increased to 200 mg/day because of inadequate clinical response. After taking prescribed dose of bupropion SR at least 14 days (median = 21 days), subjects had steady-state serial plasma levels of bupropion and its metabolites measured during a 24-hour period after morning doses. A total of 9 subjects underwent these PK assessments on doses of 100 mg/day, and 6 underwent these on doses of 200 mg/day, with 4 studied on both doses. In this 24-hour assessment, the treating psychiatrist rated subjects' antidepressant response using the Clinical Global Impression's Improvement scale (CGI-I), blind to plasma levels, but informed by child and parent rating scales of depressive symptoms and clinical interviews. Relative to 7 nonresponders, 9 responders (CGI-I < or = 2) had significantly higher mean areas under concentration curves for bupropion (P = 0.03), threohydrobupropion (P = 0.02), and erythrohydrobupropion (P = 0.02), and especially hyroxybupropion (P = 0.006). Plasma levels 7.5 hours after morning doses reaching the following cut points discriminated responders from nonresponders: bupropion > or = 37 ng/mL (P = 0.001), hydroxybupropion > or = 575 ng/mL (P = 0.003), threohydrobupropion > or = 240 ng/mL (P = 0.009), or erythrohydrobupropion > or = 45 ng/mL (P = 0.009). These preliminary findings suggest that plasma levels of bupropion and metabolites, particularly hydroxybupropion, may predict acute antidepressant response in depressed youths taking bupropion SR.
Administration, Oral↗
A comparison of the medical lethality of suicide attempts in bipolar and major depressive disorders.
OBJECTIVES: Among mood disorders, bipolar disorder (BPD) is often noted to involve the highest rates of suicide attempts and possibly of completion. This study sought to determine whether suicide attempters with BPD exhibit suicide attempts with higher lethality than attempters with major depressive disorder (MDD) and to explore differences in clinical features associated with suicidal acts. METHODS: Mood disordered suicide attempters were interviewed about Axis I and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal ideation, the medical lethality of their most severe suicide attempt, severity of depression, hopelessness, lifetime aggression, and impulsivity. RESULTS: The maximum lethality of suicidal acts tended to be higher among BPD attempters compared with those with MDD. However, there were no differences in the number of suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD reported higher levels of aggression and impulsivity but less hopelessness compared with MDD attempters. These differences could not be explained by Cluster B personality disorder comorbidity. Of note, within the BPD group, but not the MDD group, males reported suicidal acts with higher lethality. Multivariate analyses suggested that risk for more lethal suicide attempts is associated with BPD and male sex and that bipolar males appear to be especially vulnerable to these behaviors. CONCLUSIONS: Males with BPD make more lethal suicide attempts than females with BPD, an effect not observed among the MDD sample. Our findings suggest that higher rates of suicidal behavior in BPD may be due to a specific effect of BPD on males, leading to more dangerous suicidal behaviors. This effect, together with the larger proportion of males in the BPD group compared with the MDD group may lead to higher rates of reported attempted and completed suicide.
Adult↗
Criterion validity of the Mood and Feelings Questionnaire for depressive episodes in clinic and non-clinic subjects.
BACKGROUND: Previous measures of pediatric depression have shown inconsistent validity in groups with differing demographics, comorbid diagnoses, and clinic or non-clinic origins. The current study re-examines the criterion validity of child- and parent-versions of the Mood and Feelings Questionnaire (MFQ-C, MFQ-P) in a heterogeneous sample of children and adolescents from clinic and non-clinic sources. METHODS: Among 470 consecutive youth completing semi-structured interviews at a university-based child psychiatry center, total scores from the 33-item MFQ-C and 34-item MFQ-P were examined across subjects with and without mood disorders using analysis of variance, and receiver operating characteristics analysis. RESULTS: Mean scores of the MFQ-C and MFQ-P, respectively, differed significantly (p < .0005) across youth having major depressive episodes (MDE) (33 and 32, n = 77), mood disorders not meeting criteria for current MDE (24 and 28, n = 75), and no mood disorders (12 and 10, n = 318). In the overall sample, areas under the curve (AUC) for discriminating MDE and any mood disorder, respectively, were .85 and .83 on the MFQ-C, .86 and .90 on the MFQ-P, and .89 and .90 on the MFQ-C and MFQ-P averaged together, suggesting moderate to high criterion validity. Similar findings were noted in subgroups divided by age, sex, race, comorbid psychopathology, and clinic or non-clinic origins. AUCs of these MFQ scores compared favorably with those of the Beck's Depressive Inventory, the Child Behavior Checklist's Anxious/Depressed scale and the Children's Depressive Rating Scale-Revised by the same raters. A score of 29 on the MFQ-C (positive screen rate 21%, sensitivity 68%, specificity 88%) or 27 on the MFQ-P (positive screen rate 23%, sensitivity 61%, specificity 85%) optimally discriminated youth with MDE from the rest of the sample. CONCLUSIONS: The MFQ-C and MFQ-P, especially used in combination, validly identify MDE or other mood disorders in youth diverse in demographic and clinical characteristics.
Adolescent↗
Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression.
OBJECTIVE: The lower expressing allele of the serotonin transporter gene 5' promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. METHOD: Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: L(A); lower expressing alleles: L(G), S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. RESULTS: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing L(A) allele. No associations with suicidal behavior and CSF 5-HIAA were found. CONCLUSIONS: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.
Adult↗
[Depression in children and adolescents].
Early onset depression is a widely prevalent, recurrent and familial disorder with a tendency to continue throughout adulthood. It is often accompanied by other comorbidities such as substance abuse, bipolar disorder, suicidal behavior and significant impairment in the child's psychosocial development. The risk factors include genetic, psychological and environmental factors and gene-environment interaction. The evidence-based therapies include cognitive, inter-personal and pharmacological interventions. Recently, the FDA published a warning concerning the use of these pharmacological agents in the pediatric age group. Further research is needed to assess the efficacy and safety of these interventions and to better understand the etiological factors.
Adolescent↗
Family genetic studies, suicide, and suicidal behavior.
The extant adoption, twin, and family studies of suicide and suicidal behavior are reviewed. Suicidal behavior is highly familial, and on the basis of twin and adoption studies, heritable as well. Both completed and attempted suicide form part of the clinical phenotype that is familially transmitted, as rates of suicide attempt are elevated in the family members of suicide completers, and completion rates are elevated in the family members of attempters. A family history of suicidal behavior is associated with suicidal behavior in the proband, even after adjusting for presence of psychiatric disorders in the proband and family, indicating transmission of attempt that is distinct from family transmission of psychiatric disorder. Impulsive aggression in probands and family members is associated with family loading for suicidal behavior, and may contribute to familial transmission of suicidal behavior. Shared environment effects such as abuse, imitation, or transmission of psychopathology are other possible explanations.
Adoption↗
Is the medication bottle for pediatric and adolescent depression half-full or half-empty?
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Adolescent↗
Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects.
Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax and KD) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher Bmax in all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. Bmax was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT2A Bmax in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.
Adult↗
The risks and benefits of antidepressant treatment for youth depression.
The U.S. Food and Drug Administration (FDA) has mandated that all antidepressants carry a 'black box' warning label indicating that antidepressants increase the risk of suicidality in youth taking these medications. In the U.K., the Medicine and Healthcare Products Regulatory Agency (MHRA) has determined that the balance of risks and benefits favors only the use of fluoxetine in the treatment of depressive illness in children and adolescents. This article reviews the FDA's analysis linking antidepressant medication use and pediatric suicidality in major depressive disorder, discusses the efficacy of antidepressants in treating depression in children and adolescents, and offers suggestions to aid clinicians, patients, and families in making clinical decisions based on an accurate assessment of the benefits and risks of medication and psychosocial treatments for pediatric depression.
Adolescent↗
Steady-state pharmacokinetics of bupropion SR in juvenile patients.
OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.
Adolescent↗