Warren A. Weinberg

Effect Size of Lithium, Divalproex Sodium, and Carbamazepine in Children and Adolescents With Bipolar Disorder

OBJECTIVE To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years. METHOD Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS). RESULTS Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen. CONCLUSIONS Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.

Depression in children referred to an educational diagnostic center: Diagnosis and treatment

Forty-five of 72 prepubertal children presenting to an educational diagnostic clinic with school performance or behavior problems or both were diagnosed as suffering from a depressive illness (depression). Nineteen patients were given a trial on antidepressant medication. Three to 7 months later, these children showed significantly more improvement in the resolution of the problems which led to referral including depressive symptoms than either the nontreated depressed or nondepressed children. A positive family history of an affective condition was present in 40 of 45 depressed children and in 8 of 26 nondepressed children. Depressed children had a high incidence of hyperactivity, school phobia, enuresis, and other “developmental behavior problems”; such behavior often occurred only during a depressive episode.

Combination pharmacotherapy in children and adolescents with bipolar disorder

BACKGROUND The purpose of this study was to develop prospective data on the effectiveness of combination pharmacotherapy of children and adolescents with bipolar disorder during a 6-month period of prospective, semi-naturalistic treatment. METHODS Thirty-five subjects, with a mean age of 11 years, were treated in the extension phase of this study after having received 6-8 weeks of acute treatment with a single mood stabilizer. The extension phase of this study lasted for another 16 weeks, for a total of 24 weeks of prospective treatment. During this study phase, subjects were openly treated, and they could have their acute-phase mood stabilizer switched or augmented with another mood stabilizer, a stimulant, an antidepressant agent, or antipsychotic agent, if they were assessed to be a nonresponder to monotherapy with their initial mood stabilizer. RESULTS During the extension phase of treatment, 20 of 35 subjects (58%) required treatment with one or two mood stabilizers and either a stimulant, an atypical antipsychotic agent, or an antidepressant agent. The response rate to combination therapy was very good, with 80% of subjects treated responding to combination therapy with two mood stabilizers after not responding to monotherapy with a mood stabilizer. CONCLUSIONS This study suggests that children and adolescents with bipolar disorder are similar to adults with bipolar disorder, who also frequently require combination therapy.

Recurrence of Major Depressive Disorder in Hospitalized Children and Adolescents

OBJECTIVE To evaluate the outcome of a sample of children and adolescents hospitalized with major depressive disorder (MDD) and to assess different duration and severity criteria to define recovery and recurrence. METHOD Fifty-nine of 70 children and adolescents were reevaluated 1 to 5 years later, and the intervening course of depression and other disorders was assessed using the Kiddie-Longitudinal interval Follow-up Evaluation (K-LIFE). RESULTS Ninety-eight percent of subjects had recovered from their index MDD episode within 1 year of their initial evaluation, but 61% had at least one recurrence during the follow-up period. Of those with recurrences, 47.2% had a recurrence within 1 year and 69.4% by 2 years from the offset of the index episode. Changing the criteria for recovery by increasing the length of time required to define recovery resulted in decreases in the number of episodes of recurrence reported. CONCLUSION MDD in children and adolescents is often an episodic disorder. Difference in definitions of recovery and recurrence affect the data reported. Consistent definitions of remission, recovery, relapse, and recurrence are needed. These data suggest that recovery may be defined after two consecutive months without symptoms and that episodes of MDD may be briefer, but more frequent, in children and adolescents than in adults.

Primary disorder of vigilance: A novel explanation of inattentiveness, daydreaming, boredom, restlessness, and sleepiness

We present a novel condition, designated as a primary disorder of vigilance, that has symptoms which overlap those of attention deficit-hyperactivity disorder. Vigilance is the state of being watchful, awake, and alert. When vigilance is lost, the individual has difficulty sustaining attention. The most obvious evidence of lowered vigilance is motor restlessness (fidgeting and moving about, yawning and stretching, talkativeness, or a combination of these) to improve alertness when sitting or standing still or when involved in tasks requiring continuous mental performance. When prevented from being active to stay awake, persons with lowered vigilance will stare off, daydream, show minor hyperactivity, and finally may fall asleep. They will also have decreasing attention to current activities and usually avoid or lose interest in structured or repetitive activities (complaining of boredom and monotony). The primary disorder of vigilance (for which criteria have been established) is a dominantly inherited condition with onset in early childhood and worsening symptoms with age. Persons with the primary disorder of vigilance have a remarkably kind and caring temperament. When untreated this disorder can cause chronic failure at school and work, but when properly recognized it responds well to treatment with stimulant medication and schedules that avoid sameness and repetition.

Intelligence, reading achievement, physical size, and social class

A total of 334 nonreferred grade-school boys were examined for measures of physical growth, I.Q., and reading proficiency. SES was determined by the Hollingshead-Redlich index. Results of the study indicate: (1) for the total sample all physical measures significantly correlated with at least two of the three psychometric test scores; (2) SES alone accounted for 29 to 38% variance in psychometric scores; (3) mean scores of all psychometric and some physical variables significantly separated social classes: the higher the social class the greater the psychometric test scores (I.Q. and reading), HC, and height of the child; (4) holding constant SES decreased all correlations between intellectual performance and somatic growth; but (5) significant correlations remained between all physical measures and one or more psychometric scores; and (6) within individual social classes HC was the best physical predictor of WISC I.Q. and was significantly correlated with it in Classes I through IV.

Depressive symptoms by self-report in adolescence: Phase I of the development of a questionnaire for depression by self-report

As the first step in validating a criteria-based, self-report depression questionnaire specifically for children and adolescents and to determine the prevalence of self-reported depressive symptoms, we studied 3,294 high school students of mixed ethnic background in a large urban school district. They completed the Weinberg Screening Affective Scale. The 21-item Beck Depression Inventory was also completed to allow comparison with a previous study. The prevalence of clinically significant depressive symptoms suggesting depression by self-report ranged from 18% on the Beck Depression Inventory to 13% on the Weinberg Screening Affective Scale. Hispanic females had the highest scores, while white males had the lowest. Being behind in school, female, and nonwhite predicted more self-reported depressive symptoms. (J Child Neurol 1989;3:114-121).

Sleep polysomnography as a predictor of recurrence in children and adolescents with major depressive disorder.

Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.

The myth of attention deficit-hyperactivity disorder: symptoms resulting from multiple causes.

Received Oct 21, 1991. Accepted for publication Oct 29, 1991. From the Departments of Neurology and Pediatrics (Dr Weinberg), University of Texas-Southwestern Medical Center and Children’s Medical Center of Dallas, Dallas, TX and the Departments of Pathology (Neuropathology), Pediatrics, Neurology, and Psychiatry & Behavioral Sciences (Dr Brumback), University of Oklahoma College of Medicine, and Veterans Affairs Medical Center, Oklahoma City, OK. Address correspondence to Dr Warren A. Weinberg, Children’s Medical Center of Dallas, 1935 Motor Street, Dallas, TX 75235. Editor’s Note: In this issue of the Journal of Child Neurology we present the second of a new series of controversial issues in child neurology. The format consists of an initial or &dquo;primary&dquo; position paper, which is circulated

Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents

BACKGROUND It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression. METHODS Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents). RESULTS Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls. CONCLUSIONS These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.