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Biomedical subjects

T E Wilens

Publications and source records attributed to T E Wilens.

At least 19 recordsLinked to original sources
PubMed2001

Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders.

The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. RESULTS: Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo. CONCLUSIONS: These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.

Adult↗
PubMed2000

Pediatric mania: a developmental subtype of bipolar disorder?

Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

Adolescent↗
PubMed2000

Is bipolar disorder a risk for cigarette smoking in ADHD youth?

Despite emerging literature linking juvenile bipolar disorder (BPD) and substance abuse, little is known about a link between BPD and cigarette smoking. To this end, we evaluated the association between BPD and cigarette smoking in youth. Subjects were 31 bipolar adolescents derived from a cohort of boys with DSM-III-R ADHD (N = 128) and non-ADHD comparisons (N = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Logistic regression models were used to determine risk for smoking at follow-up. BPD was associated with a higher risk for cigarette smoking in mid-adolescence, which was largely accounted for by conduct disorder. The developmental onset of BPD in adolescence (age 13-18 years) conferred a greater risk for cigarette smoking compared to those youths with the onset of their BPD prepubertally (< or = 12 years; odds ratio = 10.8, p < 0.01), even after controlling for conduct disorder and other confounds. The naturalistic treatment of BPD with combined counseling and pharmacotherapy appeared to reduce the risk for cigarette smoking. BPD, particularly when it onsets in adolescence, is a significant risk factor for the early initiation of cigarette smoking in these ADHD youths. These data coupled with the literature strongly suggest that juveniles with BPD need to be carefully monitored for the early initiation of cigarette smoking and substance abuse.

Adolescent↗
PubMed2000

Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young.

Pediatric bipolar disorder is commonly mixed with co-occurring symptoms of major depression and mania. Knowledge has begun to accumulate on the treatment of the mania component, but limited information is available to guide the therapeutic approach to bipolar depression. To this end, we reviewed the medical charts of 59 patients with diagnosis of DSM-III-R bipolar disorder from an outpatient pediatric psychopharmacology clinic. Multivariate methods were used to model the probability of improvement and relapse at each visit of clinical follow-up. Serotonin-specific antidepressants were significantly associated with both an increased rate of improvement of bipolar depression-relative risk = 6.7 (1.9-23.6); p = 0.003-and a significantly greater probability of relapse of manic symptomatology-relative risk = 3.0 (1.2-7.8); p = 0.02. Although mood stabilizers improved manic symptomatology, they had no demonstrable effect on the symptoms of bipolar depression. Despite the increased risk of mood destabilization, serotonin-specific antidepressants did not interfere with the antimanic effects of mood stabilizers. Because bipolar youth commonly come to clinical practice with depression, these results underscore the importance of assessing a lifetime history of bipolar disorder in making treatment decisions in depressed youth.

Adolescent↗
PubMed2000

A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder.

OBJECTIVES: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD). METHODOLOGY: Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30 % reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression. RESULTS: Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial. CONCLUSIONS: These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events.

Adolescent↗
PubMed2000

Pemoline treatment of adolescents with attention deficit hyperactivity disorder: a short-term controlled trial.

BACKGROUND: Despite the increased recognition of attention deficit hyperactivity disorder (ADHD) in adolescents, few controlled studies have assessed treatments for this age group. Adolescent issues, such as embarrassment at receiving medication at school and experimentation with abusable substances, have accelerated efforts to find effective, well-tolerated treatments beyond traditional stimulants. Pemoline has been found effective for treating both children and adults with ADHD but has not been evaluated in adolescents with ADHD. METHODS: Twenty-one adolescents (mean age 14 years old) diagnosed with ADHD by structured and clinical interviews participated in a 10-week, double-blind crossover design study of pemoline. Dosing was optimized with robust doses up to 3 mg/kg/day in one to two doses. Clinical evaluations of ADHD, depression, anxiety, and oppositional defiant disorder (ODD) symptoms were assessed weekly. RESULTS: Adolescents with ADHD exhibited a marked response to pemoline treatment relative to placebo on the ADHD rating scale (p = 0.001), with an average reduction of 3.02 points per week of treatment. Sixty percent of adolescents responded to pemoline, compared to 11% treated with placebo. This response was independent of gender or lifetime psychiatric comorbidity. Pemoline was well tolerated, with patients averaging 2.88 mg/kg/day in two doses per day, with a mean dose at end of follow-up of 181.1 mg (SD 45.6, range 112.5-262.5 mg). Side effects were mild, and no adverse hepatic events occurred. CONCLUSIONS: These findings resemble those reported in children and adults with ADHD. This trial suggests pemoline is well tolerated and effective in adolescents and may be a particularly useful ADHD treatment for adolescents.

Adolescent↗
PubMed2000

Adjunctive donepezil in attention deficit hyperactivity disorder youth: case series.

Despite well-documented improvement in attention deficit hyperactivity disorder (ADHD) in youths with the available single and combined pharmacologic agents, a number of youths remain with residual symptomatology causing impairment in multiple domains. Recent work has suggested a potential cognitive-enhancing role of cholinergic agents in ADHD. We describe five cases of ADHD youths aged 8-17 years being treated for ADHD with the acetylcholinesterase inhibitor donepezil (Aricept), all of whom demonstrated improvement.

Adolescent↗
PubMed2000

The drug-placebo response curve: a new method for assessing drug effects in clinical trials.

Unlike many other areas of medicine, psychiatric clinical trials have no gold standard laboratory tests with which to measure drug effects. Although reliable and valid psychometric measures are available, the standard analysis of such measures obscures the clinical relevance of drug effects. In this study, the authors sought to address this problem by developing a graphical display called the drug-placebo response curve. The features of the drug-placebo response curve are described by applying it to a previously published, controlled clinical trial of desipramine in the treatment of adults with attention-deficit/hyperactivity disorder. Unlike the standard analysis, the drug-placebo response curve showed that desipramine was effective over the full range of response and that it prevented worsening, in addition to increasing the likelihood of improvement. The drug-placebo response curve provides clinically relevant information about the effect of drugs on continuous outcomes in controlled clinical trials.

Adrenergic Uptake Inhibitors↗
PubMed2000

The stimulants revisited.

Stimulants are the most often prescribed psychotropics in children and adolescents, used generally for the treatment of attention deficit/hyperactivity disorder (ADHD). In this article the authors summarize the literature on prevalence of usage, neurobiology, and pharmacology of the stimulants. Recent studies on the use of stimulants in special ADHD populations including preschoolers and adults, and co-occurring neurologic, psychiatric, and substance use disorders are cited. Clinical guidelines for the management of individuals receiving the stimulants are offered, and treatment strategies delineated for ADHD subjects with comorbidity and medication-induced adverse effects are discussed.

Adolescent↗
PubMed1999

Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder.

The objective of this study was to evaluate pharmacological approaches for attention deficit hyperactivity disorder (ADHD) in children with bioplar disorder and comorbid ADHD. The medical charts of 38 patients with diagnoses of both Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised ADHD and bipolar disorder were reviewed over multiple visits to assess improvement and prescription patterns. Logistic regression was used to model the probability of improvement at each visit, and robust standard errors were estimated in order to account for correlation among individuals using Huber's correction for clustered data. The proportion of visits at which ADHD symptoms were rated as improved following initial improvement in manic symptoms was 7.5 times greater than before initial improvement of manic symptoms. The recurrence of manic symptoms following their initial stabilization significantly inhibited ADHD response to medication. Although tricyclic antidepressants (TCAs) significantly increased the probability of ADHD improvement following mood stabilization, there was also a significant association between treatment with TCAs and relapse of manic symptoms. Our results support the hypothesis that mood stabilization is a prerequisite for the successful pharmacologic treatment of ADHD in children with both ADHD and manic symptoms. Although TCAs can be helpful in the management of ADHD children with manic symptoms, these drugs should be used with caution since they can also have a destabilizing effect on manic symptoms.

Adolescent↗
PubMed1999

Desipramine clearance in children and adolescents: absence of effect of development and gender.

OBJECTIVE: To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. METHOD: DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). RESULTS: Mean pharmacokinetic parameters for the entire population included dose (3.78 +/- 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 +/- 47.39 [micrograms/L]/[mg/kg]), and DMI clearance (0.68 +/- 1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 +/- 1.40 mg/kg, 3.83 +/- 1.68 mg/kg), weight- and dose-normalized serum concentrations (44.52 +/- 39.6 [micrograms/L]/[mg/kg], 46.34 +/- 34.89 [micrograms/L]/[mg/kg]; p = .62), and clearance (0.680 +/- 0.890 [L/kg]/hr, 0.695 +/- 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 +/- 1.55 mg, 3.39 +/- 1.84 mg), weight- and dose-normalized serum concentrations (45.15 +/- 37.76 [micrograms/L]/[mg/kg], 47.14 +/- 34.96 [micrograms/L]/mg/kg]; p = .720), and clearance (0.699 +/- 0.89 [L/kg]/hr, 0.606 +/- 0.535 [L/kg]/hr; p = .390). CONCLUSIONS: These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population.

Adolescent↗
PubMed1999

Absence of cardiovascular adverse effects of sertraline in children and adolescents.

OBJECTIVE: In a 12 week, placebo-controlled, parallel-design, multicenter study of sertraline for obsessive-compulsive disorder in 107 children and 80 adolescents, the authors prospectively assessed cardiovascular effects to doses of sertraline of < or = 200 mg/day. METHOD: Vital signs (blood pressure and heart rate) and electrocardiograph parameters (ECGs) were systematically evaluated at baseline and again throughout treatment. RESULTS: There were no clinically significant cardiovascular adverse events in any of the subjects enrolled in the study. Moreover, compared with baseline and placebo, sertraline treatment at an average dose of 167 mg did not result in any clinically meaningful changes in any ECG indices (PR, QRS, and QTc intervals), cardiac rhythm, blood pressure, or heart rate. CONCLUSIONS: These prospectively derived results support the cardiovascular safety of sertraline at doses up to 200 mg in children and adolescents.

Adolescent↗
PubMed1999

Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.

OBJECTIVE: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology. METHOD: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). RESULTS: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. CONCLUSIONS: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths.

Adolescent↗
PubMed1999

Risperidone treatment for juvenile bipolar disorder: a retrospective chart review.

OBJECTIVE: To investigate the effectiveness and tolerability of the atypical neuroleptic risperidone in the treatment of juvenile mania. METHOD: This is a retrospective chart review of outpatients with the diagnosis of bipolar disorder (DSM-IV) treated with risperidone at a university center. Response to treatment was evaluated using the Clinical Global Impression Scale (CGI) with separate assessments of mania, psychosis, aggression, and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Twenty-eight youths (mean +/- SD age, 10.4 +/- 3.8 years) with bipolar disorder (25 mixed and 3 hypomanic) who had been treated with risperidone were identified. These children received a mean dose of 1.7 +/- 1.3 mg over an average period of 6.1 +/- 8.5 months. Using a CGI Improvement score of < or = 2 (very much/much improved) to define robust improvement, 82% showed improvement in both their manic and aggressive symptoms, 69% in psychotic symptoms, but only 8% in ADHD symptoms. CONCLUSIONS: Although limited by its retrospective nature, this study suggests that risperidone may be effective in the treatment of manic young people and indicates the need for controlled clinical trials of risperidone and other atypical neuroleptics in juvenile mania.

Adolescent↗
PubMed1999

Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources.

OBJECTIVE: The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD: Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS: Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS: These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.

Adolescent↗
PubMed1999

Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder.

Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.

Adult↗