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Biomedical subjects

B Birmaher

Publications and source records attributed to B Birmaher.

At least 37 records · Page 2Linked to original sources

Anxiety disorders in suicidal youth.

OBJECTIVE: To test the hypothesis that anxiety disorders are associated with suicidal ideation and suicide attempts in a child and adolescent sample referred to a clinic. METHOD: The sample comprised 1979 patients aged 5 to 19 years who were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children--Present Episode (K-SADS-P) at an outpatient mood and anxiety disorders clinic. Subjects were stratified by age and categorized into mutually exclusive groups as being nonsuicidal (n = 817), having suicidal ideation (n = 768), or having attempted suicide (n = 394) in the current episode. Psychiatric diagnoses based on DSM-IV criteria were compared to determine if anxiety disorders were a risk factor for suicidal ideation and suicide attempts. Logistic regression was used to control for significant demographic characteristics and comorbid disorders. RESULTS: After stratifying by age, we found no differences across the 3 groups (ideators, attempters, and nonsuicidal youth) in rates of an anxiety disorder in general or in specific rates of panic disorder, agoraphobia, social phobia, simple phobia, and obsessive-compulsive disorder. Two salient findings involving anxiety disorders were noted with regression analysis. In younger children (age < or = 15 years), attempters had a significantly lower prevalence of separation anxiety disorder (SAD), compared with ideators (OR = 0.30; 95%CI, 0.11 to 0.80; P = 0.006) and nonsuicidal youngsters (OR = 0.14; 95%CI, 0.05 to 0.39; P < 0.0001). In older children (age > 15 years), generalized anxiety disorder (GAD) was more prevalent in ideators (OR = 1.65; 95%CI, 1.03 to 2.66; P = 0.03) than in nonsuicidal patients. CONCLUSIONS: Based on this clinical sample, the relation between pediatric anxiety disorder and suicidal ideation and suicide attempts is not straightforward. However, further studies in nonreferred samples are warranted.

Adolescent↗

Cognitive and family therapies for adolescent depression: treatment specificity, mediation, and moderation.

The specificity of cognitive and family therapies, and potential treatment mediators and moderators, was examined in a randomized clinical trial for adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT) exerted specific effects on cognitive distortions relative to either systemic-behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2-year follow-up, SBFT was found to impact family conflict and parent-child relationship problems more than CBT; NST and CBT tended to show a greater reduction in anxiety symptoms than SBFT. Nonspecific therapist variables qualified few outcome analyses. No measures of cognitive distortion or family dysfunction mediated or moderated treatment outcome. As in adult studies, relatively few areas of treatment specificity or mediation were identified. The implications of these findings for clinical treatment and research in adolescent depression are discussed.

Adolescent↗

Prolactin secretion in depressed children.

BACKGROUND: Few studies have examined the involvement of the central dopaminergic system in the pathophysiology of mood disorders. The study of prolactin (PRL) secretion may be an informative indirect method for the assessment of the dopaminergic system in children with major depressive disorder (MDD). METHODS: Plasma PRL concentrations were measured at 20-min intervals over a 24-hr period in 40 pre-pubertal children with MDD, 18 with non-affective psychiatric disorders (PC), and 6 normal controls (NC). A subgroup of depressed children (n = 21) was restudied after recovery. RESULTS: There was no significant differences in either the amount or the pattern of PRL secretion between the MDD, PC, and NC groups. Children who recovered from their depression secreted less PRL during sleep and more while awake compared to when they were acutely depressed. CONCLUSIONS: Overall, there were no differences in baseline PRL secretion between children with MDD, NC and psychiatric control. These results suggest that the dopaminergic system as measured by baseline PRL blood levels is not compromised in children with MDD.

Anxiety Disorders↗

A.E. Bennett Research Award. Developmental traumatology. Part I: Biological stress systems.

BACKGROUND: This investigation examined the relationship between trauma, psychiatric symptoms and urinary free cortisol (UFC) and catecholamine (epinephrine [EPI], norepinephrine [NE], dopamine [DA]) excretion in prepubertal children with posttraumatic stress disorder (PTSD) secondary to past child maltreatment experiences (n = 18), compared to non-traumatized children with overanxious disorder (OAD) (n = 10) and healthy controls (n = 24). METHODS: Subjects underwent comprehensive psychiatric and clinical assessments and 24 hour urine collection for measurements of UFC and urinary catecholamine excretion. Biological and clinical measures were compared using analyses of variance. RESULTS: Maltreated subjects with PTSD excreted significantly greater concentrations of urinary DA and NE over 24 hours than OAD and control subjects and greater concentrations of 24 hour UFC than control subjects. Post hoc analysis revealed that maltreated subjects with PTSD excreted significantly greater concentrations of urinary EPI than OAD subjects. Childhood PTSD was associated with greater co-morbid psychopathology including depressive and dissociative symptoms, lower global assessment of functioning, and increased incidents of lifetime suicidal ideation and attempts. Urinary catecholamine and UFC concentrations showed positive correlations with duration of the PTSD trauma and severity of PTSD symptoms. CONCLUSIONS: These data suggest that maltreatment experiences are associated with alterations of biological stress systems in maltreated children with PTSD. An improved psychobiological understanding of trauma in childhood may eventually lead to better treatments of childhood PTSD.

Adolescent↗

Use of selective serotonin reuptake inhibitors for the treatment of childhood panic disorder: a pilot study.

This preliminary study examines the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs) for the treatment of panic disorder in children and adolescents. In a prospective open label study, 12 children and adolescents with panic disorder were treated with SSRIs, and if necessary, with benzodiazepines, for a period of 6-8 weeks and were followed for approximately 6 months. During the trial, clinician-based and self-report rating scales for anxiety and depression, functioning, and side effects, were administered. Using the Clinical Global Impression Scale (CGIS) 75% of patients showed much to very much improvement with SSRIs without experiencing significant side effects. After controlling for changes in depressive symptoms, self-report and clinician-based anxiety scales also showed significant improvement. At the end of the trial, 67% of patients no longer fulfilled criteria for panic disorder and 4 patients remained with significant residual symptoms. In conclusion, SSRIs appear to be a safe and promising for the treatment of children and adolescents with panic disorder, however, randomized controlled trials evaluating the effects of SSRIs and other interventions (e.g., cognitive therapy) for treating panic disorder in children and adolescents are warranted. It appears that until the SSRIs begin to exert their effects, a benzodiazepine adjunct treatment might be helpful for patients with severe panic disorder.

Adolescent↗

A clinical trial for adolescent depression: predictors of additional treatment in the acute and follow-up phases of the trial.

OBJECTIVE: To examine the predictors of additional service use among participants in a clinical trial for depression. METHOD: 107 adolescents with DSM-III-R depression were randomly assigned to receive either cognitive-behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy for 12 to 16 weeks of acute treatment and followed up periodically for 24 months after the termination of acute treatment. RESULTS: More than half (53.3%) of the 107 randomized adolescents received additional treatment beyond that provided in the clinical trial, with a median time to additional treatment from intake of 7.2 months. The rates and times to additional treatment were similar in the 3 treatment groups, despite the superior efficacy of cognitive-behavioral therapy in the acute phase. The severity of the index depressive episode and comorbid dysthymia were a predictor of additional treatment in the acute phase, whereas in the follow-up period the severity of depressive symptomatology, the presence of disruptive disorders, and family problems predicted additional treatment. CONCLUSIONS: Subsequent clinical trials for early-onset depression must focus on the entire depressive episode, rather than just the acute phase, to prevent depressive relapse. In addition, attendant family difficulties and comorbid behavioral problems must be addressed.

Acute Disease↗

Suicide in adolescents with disruptive disorders.

OBJECTIVE: To determine the psychiatric risk factors for suicide in adolescents with disruptive disorders. METHOD: Fifty-nine adolescent suicide completers and 18 community controls, both having a probable or definite current DSM-III diagnosis of disruptive disorders, were compared. RESULTS: Adolescents with disruptive disorders who committed suicide had higher rates of current substance abuse, past suicide attempt, family history of substance abuse, and family history of mood disorder than disruptive community controls. CONCLUSIONS: Disruptive adolescents appear to be at risk for completed suicide when comorbid substance abuse and past history of suicide attempt are present. The risk increases if the adolescents have a past history of physical abuse and if they have parents with substance abuse and mood disorders. Clinicians should be aware of these risk factors and implement active interventions to prevent suicide. Treatment should focus on treating not only the adolescents, but also their family members. The findings of this study also highlight the need for future research in the prevention of suicide in adolescents with disruptive disorders and comorbid substance abuse.

Adolescent↗

Factors associated with the development of substance use disorder in depressed adolescents.

OBJECTIVE: To document rates of substance use disorders (SUD) in adolescents with unipolar major depressive disorder and to examine demographic, clinical, and biological factors associated with the development of SUD. METHOD: Twenty-eight adolescents with unipolar major depression and no SUD history and 35 group-matched normal controls who participated in a cross-sectional sleep polysomnography and neuroendocrine study were reassessed clinically 7 years later. RESULTS: The risk for SUD was high in both groups (34.6% in the depressed group and 24.2% in the controls). Depressed adolescents had earlier onset of SUD than controls. Depressed adolescents who developed SUD had more significant psychosocial impairment than depressed adolescents who did not develop SUD. More anxiety traits and elevated cortisol secretion near sleep onset were associated with SUD in depressed teenagers, whereas less emotional responsiveness to exciting stimuli and higher density of eye movements during REM sleep were related to depression without SUD. CONCLUSIONS: Depressed adolescents who have anxiety traits and whose hypothalamic-pituitary-adrenal axis is active when the system is normally quiescent may be at risk for developing SUD. Co-occurrence of depression and SUD is associated with serious psychosocial morbidity. Identification of risk factors for SUD in depressed teenagers may be helpful in developing more effective treatment and prevention programs.

Adolescent↗

Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study.

OBJECTIVE: To replicate and extend work on the psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED), a child and parent self-report instrument used to screen for children with anxiety disorders. METHOD: The 41-item version of the SCARED was administered to a new sample of 190 outpatient children and adolescents and 166 parents. The internal consistency, discriminant, and convergent validity were assessed. In addition, using discriminant function analysis, a briefer version of the SCARED was developed. RESULTS: Using item analyses and factor analyses on the 41-item version, 5 factors were obtained: panic/somatic, generalized anxiety, separation anxiety, social phobia, and school phobia. In general, the total score and each of the 5 factors for both the child and parent SCARED demonstrated good internal consistency and discriminant validity (both between anxiety and depressive and disruptive disorders and within anxiety disorders). A reduced version of the SCARED yielded 5 items and showed similar psychometrics to the full SCARED. CONCLUSIONS: In a new sample, the authors replicated their initial psychometric findings that the SCARED is a reliable and valid instrument to screen for childhood anxiety disorders in clinical settings. Furthermore, pending future research, the 5-item SCARED appears to be a promising brief screening inventory for anxiety disorders in epidemiological studies.

Adolescent↗

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗

Neuropsychological study of frontal lobe function in psychotropic-naive children with obsessive-compulsive disorder.

OBJECTIVE: The authors' goal was to evaluate cognition in children with obsessive-compulsive disorder (OCD) early in their illness. METHOD: They administered neuropsychological tests to 21 pediatric patients with OCD and 21 healthy children matched for age, sex, socioeconomic status, and intelligence. The children with OCD were not depressed, and none had ever received psychotropic medication. The neuropsychological tests were used to assess the relationship between psychiatric symptoms and cognitive function. RESULTS: The children with OCD performed as well as the healthy children on the neuropsychological tests. Psychiatric symptoms and cognitive performance were not related. CONCLUSIONS: Nondepressed children with recently diagnosed OCD who had never received psychotropic medication demonstrated no cognitive impairment according to their performance on neuropsychological tests. The authors conclude that OCD symptoms may not interfere with cognitive abilities early in the illness.

Age of Onset↗

A risk-benefit assessment of pharmacotherapies for clinical depression in children and adolescents.

Child and adolescent major depressive disorders are common and recurrent disorders. The prevalence of major depressive disorders is estimated to be approximately 2% in children and 4 to 8% in adolescents. Major depressive disorders in children are frequently accompanied by other psychiatric disorders, poor psychosocial outcome and a high risk of suicide and substance abuse, indicating the need for effective treatment and prevention. The use of antidepressant medications as the first line of treatment for children and adolescents with mild to moderate major depressive disorders has been questioned. However, some subgroups of patients may benefit from initial treatment with antidepressants. These subgroups may include patients who are unwilling or unable to undergo psychotherapy, have not responded to at least 8 to 12 sessions of psychotherapy, have bipolar, atypical or severe depression or have recurrent depression. Currently, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors are the first medication choice because of their efficacy, benign adverse effect profile, ease of use and low risk of death following an overdose. Further research in continuation and maintenance treatments, treatment of comorbid conditions, subtypes of depression, e.g. bipolar, atypical, seasonal, and combinations of pharmacotherapy and psychotherapy are needed. In addition, studies of the pharmacokinetics, pharmacodynamics and long term adverse effects of antidepressant medications in children and adolescents are warranted.

Adolescent↗

Serotonergic functioning in depressed abused children: clinical and familial correlates.

BACKGROUND: The goal of this study was to examine serotonergic functioning and concomitant clinical and familial correlates in depressed abused children. METHODS: L-5-Hydroxytryptophan (L-5-HTP) (0.8 mg/kg) was administered intravenously to 10 depressed abused (MDD-AB), 10 depressed nonabused (MDD-NA), and 10 normal control nonabused (NC-NA) children. The children in the two nonabused cohorts represent a small matched subset of children from a larger interlocking study of the psychobiology of depression. Blood samples for prolactin and cortisol were collected from 30 min before to 2.5 hours after L-5-HTP infusion. RESULTS: The MDD-AB children secreted significantly more prolactin post-L-5-HTP than the children in the other two groups. There were no differences in baseline prolactin or any of the cortisol measures. Total prolactin post-L-5-HTP was significantly correlated with clinical ratings of aggressive behavior (rho = .48). In addition, children with a family history positive for suicide attempt (MDD-AB: n = 7; MDD-NA: n = 5; NC-NA: n = 2) secreted significantly more prolactin post-L-5-HTP than children with no family history of suicide. CONCLUSIONS: Dysregulation in the serotonergic system in abused children appears to be related to both familial and experiential factors.

5-Hydroxytryptophan↗

Pharmacologic treatment for children and adolescents with anxiety disorders.

Pediatric anxiety disorders are common illnesses that, if left untreated, may induce academic, family, and interpersonal problems. Cognitive-behavioral techniques and other psychotherapeutic interventions may be adequate for the treatment of most anxiety disorders. For patients with severe symptoms or for whom psychotherapeutic approaches are not adequate, medications are indicated. Among the available medications, the SSRIs are currently the first choice; however, other medications, such as the benzodiazepines and the TCAs, may be used alone or sometimes in combination with the SSRIs. Caution with respect to medication interactions and side effects is indicated. In particular, long-term side effects in these medications have not been well studied.

Adolescent↗

Psychopathology in the relatives of depressed-abused children.

OBJECTIVE: To determine if the type of symptomatology abused children manifest is related to family history of psychopathology. METHOD: Lifetime history of psychopathology was assessed in the relatives of 26 preadolescents--13 depressed abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder in the relatives of these children were compared to published rates of psychopathology in relatives of 27 normal control (NC) children. Data were obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and 503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule for Affective Disorders and Schizophrenia was used to assess psychopathology in parents, and Family History method was used to obtain lifetime psychiatric data for all other relatives. RESULTS: When compared to first-degree relatives of NC children, first-degree relatives of MDD-AB children had approximately a nine-fold increased risk for major depression, and a three- to nine-fold increased risk for other disorders associated with the familial subtype of affective illness known as Depression Spectrum Disease (e.g., antisocial personality, alcohol and substance dependence). Similar findings were reported in second-degree relatives, and comparisons between the relatives of MDD-NA and NC children. CONCLUSION: The findings extend results of prior research and (1) suggest familial vulnerability factors influence the symptom profile of abused children; and (2) highlight the value of incorporating psychiatric formulations into multidisciplinary models of child abuse research and treatment programs.

Adolescent↗

Combination treatment with clomipramine and selective serotonin reuptake inhibitors for obsessive-compulsive disorder in children and adolescents.

Medication management of obsessive-compulsive disorder (OCD) has consisted of monotherapy with either clomipramine (CMI) or selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine, paroxetine, or sertraline. Frequently, OCD patients receiving monotherapy experience low treatment response rates and problematic side effects that may result in discontinuation or noncompliance. This open-label case series presents 7 patients (6 male, 1 female) ages 9 to 23 years with OCD who were effectively treated with combination of CMI plus an SSRI. Treatment effects persisted through 5 to 22 months of follow-up from onset of combination therapy. The drug combination was effective in the 2 patients with OCD and no mood/anxiety comorbidity. Side effects appeared in 5 of 7 patients; cardiovascular side effects were the most common adverse effects. Two patients had prolongation of QTc intervals and 2 developed tachycardia while taking CMI and SSRI combinations. Other risks might include serotonin syndrome, manic switch, insomnia, and possibly headaches, EPS, and sexual dysfunction. Recommendations are made to monitor electrocardiograms, CMI blood concentrations, and vital signs in all cases because SSRIs can increase the blood levels of CMI and/or its active metabolite, desmethylclomipramine (DCMI). CMI could also potentially increase SSRI absorption and/or protein binding. The use of CMI and SSRI combination therapy was found to be more effective compared with their monotherapy in all 7 cases.

Adolescent↗

Manic behaviors associated with fluoxetine in three 12- to 18-year-olds with obsessive-compulsive disorder.

In a sample of 40 youths (ages 11-17) with obsessive-compulsive disorder (OCD) and mood disorders who were treated with behavior therapy, 20 patients received serotonin reuptake inhibitors (SRIs) and 20 did not. In open-label clinical treatment, 30% of the patients (6/20) treated with SRIs developed manic or hypomanic symptoms (5/15 on fluoxetine, 1/1 on sertraline). Symptoms included impulsivity, grandiosity, pressured speech, and disinhibition and did not resemble akathisia or "behavioral activation." These behaviors emerged despite gradual dose elevation (2-5 mg/wk), conservative dosing (maximum 40 mg daily), and careful weekly outpatient monitoring of each patient. Fluoxetine-induced mania occurred at doses as low as 10 mg daily. It is unclear whether mania/hypomania would appear in OCD children without comorbid mood disorders or, alternatively, whether OCD is a stronger risk factor than mood disorder for manic switch in SRI-treated youths. Clinicians are advised to be aware of the risk and to be vigilant in monitoring manic and hypomanic behaviors when using SRIs to treat OCD in youth, even with low doses and gradual dose elevation.

Adolescent↗

Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression.

OBJECTIVE: To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). METHOD: Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo. RESULTS: There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL. CONCLUSIONS: No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD.

Adolescent↗