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Biomedical subjects

Timothy E Wilens

Publications and source records attributed to Timothy E Wilens.

16 recordsLinked to original sources
PubMed2003

An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder.

BACKGROUND: Despite the increasing recognition of comorbid attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) in adults, there are no prospective trials of pharmacological agents to treat ADHD in these patients. Given the efficacy of bupropion for ADHD in adults, as well as its use in the management of bipolar depression, we studied the tolerability and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD. METHODS: This was an open, prospective, 6-week trial of bupropion SR (up to 200 mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I) (10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic agents (mood stabilizers and antipsychotics) at baseline were included in the study. We used standardized psychiatric instruments for diagnosis and outcome. Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for ADHD and the ADHD symptom checklist. RESULTS: Of 36 patients entered (75% male, mean age 34 years), 30 patients (83%) completed the protocol. At end point (last observation carried forward [LOCF]) compared to baseline, treatment with bupropion SR resulted in significant reductions in the ADHD symptom checklist (-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001). Bupropion was associated with reductions in ratings of mania and depression. CONCLUSIONS: The results from this open study of adults with ADHD plus BPD suggest that sustained-release bupropion may be effective in treating ADHD in the context of a lifetime diagnosis of BPD, without significant activation of mania. Further controlled trials are warranted.

Adult↗
PubMed2003

Can adults with attention-deficit/hyperactivity disorder be distinguished from those with comorbid bipolar disorder? Findings from a sample of clinically referred adults.

BACKGROUND: Despite data describing the overlap of attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in youth, little is known about adults with these co-occurring disorders. We now evaluate the clinical characteristics of referred adults with (n = 24) and without BPD (n = 27). METHODS: Referred adults to clinical trials of ADHD were evaluated by psychiatric evaluation using DSM-IV criteria. Structured psychiatric interviews were used to systematically assess adult and childhood disorders. RESULTS: The vast majority of patients with ADHD plus BPD had bipolar II disorder (88%). Adults with ADHD plus BPD had higher rates of the combined subtype of ADHD compared to ADHD without BPD (chi(2) = 8.7, p =.003), a greater number of DSM-IV ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0; t = -3.4, p <.01), more attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/- 2.1; t = -2.5, p <.02; trend), poorer global functioning (47 +/- 5.9 and 52 +/- 7.4, t = 2.6, p <.02; trend), and additional comorbid psychiatric disorders (3.7 +/- 2.5 and 2.0 +/- 1.9; t = -2.9, p <.01). CONCLUSIONS: These results suggest that adults with ADHD plus BPD have prototypic symptoms of both disorders, suggesting that both disorders are present and are distinguishable clinically.

Adult↗
PubMed2003

Current concepts in the validity, diagnosis and treatment of paediatric bipolar disorder.

Despite ongoing controversy, the view that paediatric bipolar disorder is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that paediatric bipolar disorder may not be rare but that it may be difficult to diagnose. Since children with bipolar disorder are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset bipolar disorder may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. As recommended by Robins and Guze [American Journal of Psychiatry (1970), 126, 983-987], a psychiatric disorder may be considered a valid diagnostic entity if it can be shown to have differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The goal of this article is to review our work and the extant literature within this framework to describe the evidence supporting bipolar disorder in children as a valid clinical diagnosis.

Attention Deficit Disorder with Hyperactivity↗
PubMed2003

A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors.

OBJECTIVE: Despite a rapidly growing literature on the efficacy of the selective serotonin reuptake inhibitors (SSRI) in the treatment of juvenile psychiatric disorders, relatively little is described about emotional, behavioral, and cognitive adverse effects associated with their use. To this end we completed a retrospective analysis of medical charts to determine the incidence, nature, and clinical correlates of treatment emergent adverse effects in the behavioral, cognitive, and emotional domains. METHODS: We systematically evaluated the medical charts of children treated with SSRI for depressive or obsessive-compulsive disorders for a mean (+/- SD) of 26.9 + 20.8 months to determine the incidence, nature, and clinical correlates of treatment emergent psychiatric adverse events (PAE). Charts were reviewed for diagnoses, type and dose of SSRI and adjunct medication, specific type of PAE, and time to onset and offset of PAE. RESULTS: In total, 82 charts of children and adolescents (mean age 12.2 +/- 3.2 years) were examined. PAE occurred in 22% of children and were most commonly related to disturbances in mood. PAE were not associated with psychiatric diagnosis(es), age, sex, concurrent medications, doses or specific serotonin reuptake inhibitors. The onset of PAE was observed typically 3 months after SSRI exposure (median = 91 days). Although PAE diminished with SSRI discontinuation, those that emerged early in treatment diminished significantly more rapidly than those that emerged later (median offset was 10 and 49 days, respectively). Re-exposure to an SSRI resulted in another PAE in 44% (n = 18) of the group. CONCLUSION: Based on the retrospective review of medical charts, youth receiving SSRI appear to be at risk for treatment emergent PAE and recurrence with re-exposure to an SSRI. Prospective longer term studies evaluating the course and prognosis of youths manifesting PAE to SSRI are necessary.

Adolescent↗
PubMed2003

Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature.

OBJECTIVE: Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. METHODS: A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. RESULTS: Six studies--2 with follow-up in adolescence and 4 in young adulthood--were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. CONCLUSION: Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders.

Adolescent↗
PubMed2002

Temporal association between childhood psychopathology and substance use disorders: findings from a sample of adults with opioid or alcohol dependency.

Adults with substance use disorders (SUD; alcohol or drug abuse or dependence) were evaluated to determine if childhood-onset psychopathology preceded the onset of SUD. Using structured psychiatric interviews, we assessed 47 clinically referred adults with SUD (27 with opioid dependence and 20 with alcohol dependence), with attention to childhood-onset psychopathology. A sequence of psychopathology and SUD was reconstructed using mean diagnosis onset data. Sixty-two percent of the 47 SUD adults (mean age 39.3+/-6.6 years) had early-onset SUD (defined as < or = 18 years) and 38% had late-onset SUD (> or = 19 years at onset). Psychopathology preceded the onset of SUD in 56% of adults. Attention deficit/hyperactivity disorder, multiple anxiety, and disruptive disorders typically preceded the onset of SUD; in contrast, mood disorders (specifically depressive and bipolar disorders) followed the onset of SUD. The majority of clinically referred adults with SUD had psychopathology that began in childhood, frequently preceding the onset of their SUD. These findings further highlight the importance of targeting antecedent disorders for preventive and early intervention programs aimed at reducing the risk for SUD.

Adult↗
PubMed2002

A family study of the high-risk children of opioid- and alcohol-dependent parents.

In this article, the author sought to use a high-risk study design focused on the children of parents with opioid or alcohol use disorders and children of parents with no substance use disorder (SUD) to evaluate the specificity of the risk conferred by the type of parental SUD. Using structured psychiatric interviews, cognitive assessments, and measures of social, academic, and family functioning, the authors studied 96 families (187 parents and 183 children, mean age of 11.6 years). Sixteen families had parental opioid dependence (22 children, 64% male), 14 families had parental alcohol dependence (22 children; 59% male), and 66 families had no SUD (controls; 139 children; 58% male). Fifty-nine percent of children of opioid-dependent parents had at least one major psychopathological condition, compared to 41% of the alcohol group and 28% of the control group (p < 0.01). The children of opioid- and alcohol-dependent parents were of lower socioeconomic status and had significantly more diffculties in academic, social, and family functioning than did controls. Children of opioid- and alcohol-dependent parents have significantly higher rates of psychopathology as well as more difficulties in academic, social, and family functioning compared to the children of non-SUD parents. In addition, notable trends emerged for the opioid group to have more psychopathology and functional impairment than the alcohol group. With a growing consensus that certain risk factors for later SUD start in childhood with potentially treatable childhood-onset disorders, new preventive approaches for individuals at risk may be developed targeting childhood precursors of

Alcoholism↗
PubMed2002

Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD.

OBJECTIVE: Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. METHOD: Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. RESULTS: We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD. Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. CONCLUSIONS: The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary.

Attention Deficit Disorder with Hyperactivity↗
PubMed2002

Patterns of psychopathology and dysfunction in clinically referred preschoolers.

Despite the growing interest in the use of psychotropic medications in preschoolers, little is known about the clinical presentation of young children referred for psychiatric services. We describe the clinical characteristics, psychiatric disorders, and functioning of preschoolers referred for pediatric psychiatry evaluation. Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed on clinically referred youth. Family, social, and overall functioning were assessed at intake. From the pool of 1658 consecutive referrals, we identified 200 children less than or equal to (<or=) 6 years of age (12%). The most common psychopathology identified was attention deficit hyperactivity disorder (ADHD) (86%), followed by other disruptive behavioral (61%), mood (43%), and anxiety disorders (28%). Co-occurring psychiatric disorders were common with preschoolers manifesting a mean of two major psychiatric disorders per child. Despite their young age, the onset of psychopathology preceded evaluation by a mean (+/-SD) of 2.2 +/- 1.3 years. Preschoolers referred for psychiatric services had high rates of psychopathology with prominent comorbidity and associated dysfunction. These preschoolers are likely to require aggressive interventions including psychopharmacology.

Anxiety Disorders↗
PubMed2002

Fluoxetine pharmacokinetics in pediatric patients.

The objective of this study was to evaluate the pharmacokinetic profile of fluoxetine (FLX) and its major metabolite, norfluoxetine (NORFLX), in children and adolescent patients undergoing psychiatric treatment. Twenty-one pediatric subjects--10 children (6-12 years) and 11 adolescents (13-18 years)--were administered 20 mg FLX for 60 days, with sparse blood samples taken throughout the open-label study. Subjects contributed 168 plasma concentrations. Pharmacokinetic parameters were estimated using a mixed effects nonlinear model. Mean steady-state FLX and NORFLX of 127 ng/mL and 151 ng/mL, respectively, were achieved in children and adolescents after 4 weeks of treatment, with high between-patient variability. FLX was 2-fold higher and NORFLX was 1.7-fold higher in children relative to adolescents; however, when normalized to body weight, FLX and NORFLX were similar for both age groups. Age, body weight, body mass index, and body surface area, modeled independently as continuous variables, significantly improved the population pharmacokinetic model when evaluated as patient factors. Body weight was the covariate retained in the final model. In conclusion, children have 2-fold higher FLX and NORFLX relative to adolescents that appear to be related to indices of body size. The accumulation profile and steady-state concentrations in adolescents appear similar to those in adults.

Adolescent↗
PubMed2002

Attention deficit/hyperactivity disorder across the lifespan.

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder presenting for treatment in youth. ADHD is often chronic with prominent symptoms and impairment spanning into adulthood. ADHD is often associated with co-occurring anxiety, mood, and disruptive disorders, as well as substance abuse. The diagnosis of ADHD by careful review of symptoms and impairment is both reliable and valid. Recent genetic, imaging, neurochemistry, and neuropsychological data support the biological underpinning of the disorder. All aspects of an individual's life must be considered in the diagnosis and treatment of ADHD. Pharmacotherapy, including stimulants, antidepressants, and antihypertensives, plays a fundamental role in the management of ADHD across the lifespan.

Adolescent↗
PubMed2002

Influence of gender on attention deficit hyperactivity disorder in children referred to a psychiatric clinic.

OBJECTIVE: The substantial discrepancy in the male-to-female ratio between clinic-referred (10 to 1) and community (3 to 1) samples of children with attention deficit hyperactivity disorder (ADHD) suggests that gender differences may be operant in the phenotypic expression of ADHD. In this study the authors systematically examined the impact of gender on the clinical features of ADHD in a group of children referred to a clinic. METHOD: The study included 140 boys and 140 girls with ADHD and 120 boys and 122 girls without ADHD as comparison subjects. All subjects were systematically assessed with structured diagnostic interviews and neuropsychological batteries for subtypes of ADHD as well as emotional, school, intellectual, interpersonal, and family functioning. RESULTS: Girls with ADHD were more likely than boys to have the predominantly inattentive type of ADHD, less likely to have a learning disability, and less likely to manifest problems in school or in their spare time. In addition, girls with ADHD were at less risk for comorbid major depression, conduct disorder, and oppositional defiant disorder than boys with ADHD. A statistically significant gender-by-ADHD interaction was identified for comorbid substance use disorders as well. CONCLUSIONS: The lower likelihood for girls to manifest psychiatric, cognitive, and functional impairment than boys could result in gender-based referral bias unfavorable to girls with ADHD.

Adolescent↗
PubMed2002

A review of the pharmacotherapy of adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, the use of pharmacotherapeutics remains less established. METHODS: A systematic review of the literature identified 15 studies (N = 435 subjects) of stimulants, and 22 studies of non-stimulant medications (N = 421 subjects) including antidepressants, antihypertensives, amino acids, and wake-promoting agents for the treatment of ADHD in adults. RESULTS: Studies with stimulants and antidepressants demonstrated significant short-term improvement in ADHD symptoms compared to placebo in adults. Methylphenidate (MPH) and amphetamine had an immediate onset of action whereas the ADHD response to pemoline and antidepressants appeared delayed. The response to amphetamine and MPH appears to be dose-dependent. Controlled data on nicotonic and noradrenergic compounds appear promising. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. CONCLUSIONS: Under controlled conditions, the aggregate literature shows that the stimulants and noradrenergic antidepressants had a clinically and statistically significant beneficial effect on treating ADHD in adults.

Adult↗
PubMed2002

Overview and neurobiology of attention-deficit/hyperactivity disorder.

Although attention-deficit/hyperactivity disorder (ADHD) impairs millions of people worldwide, both the prevalence and existence of the disorder are being reevaluated at the phenotypic level. To safeguard against overdiagnosis, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), demands that individuals with ADHD have pervasive impairment, that is, impairment in more than 1 setting. However, the appropriateness of the DSM-IV classification of ADHD is also undergoing reevaluation. Like the symptoms of a developmental disability, the symptoms of ADHD must be evaluated in the context of age-based norms; therefore, the current criteria for ADHD, which are not age referenced, may minimize the rate of persistence of ADHD into adulthood. In an effort to better understand the pathophysiology of ADHD, recent research has focused on identifying the etiology of ADHD. These studies have revealed that the disorder is highly heritable and may be associated with neurobiological deficits in the prefrontal cortex and related subcortical systems. Etiologic studies have also identified candidate genes and prenatal and perinatal risk factors for ADHD. As the causes and course of ADHD are better understood, a new generation of medications is being developed for the disorder. Although stimulants are often effective in reducing the symptoms of the disorder, as a class they have limitations such as a lack of 24-hour-a-day coverage, unwanted side effects, potential for abuse, and lessened effectiveness in the context of some comorbidities. Therefore, the treatment characteristics of newer, more selective treatments such as atomoxetine should continue to be explored in ADHD.

Adult↗
PubMed2002

Novel treatments for attention-deficit/hyperactivity disorder in children.

Optimal medications for children with attention-deficit/hyperactivity disorder (ADHD) would be effective, well tolerated, and long acting and not cause mood swings or worsen comorbid conditions. Current medications work on brain dopamine and/or norepinephrine systems, which are thought to be involved in ADHD. The medication class with the most evidence of efficacy in ADHD is stimulants, but they may be abused, are effective for only 4 to 12 hours, and may cause mood swings or increase tic severity. In recent years, alternative treatments have been explored. Tricyclic antidepressants have efficacy comparable to that of stimulants but may cause constipation, dry mouth, tremors, blood pressure changes, and potentially serious side effects including cardiac conduction and repolarization delays. Monoamine oxidase inhibitors may improve ADHD symptoms but are associated with severe dietary restrictions. Serotonin reuptake inhibitors have little or no effect in ADHD but may improve comorbid depression. Bupropion, although less effective than stimulants, may improve both ADHD symptoms and comorbid depression. Antihypertensive agents may improve impulsivity, hyperactivity, and comorbid tics but cause sedation or rebound hypertension. Atomoxetine, which is being developed for ADHD, reduces symptoms of ADHD without exacerbating comorbid conditions and is associated with only minor side effects, including subtle changes in blood pressure and heart rate. Before prescribing a treatment, physicians should consider the appropriateness and effectiveness of any medication for children with ADHD, who may be less tolerant of side effects and less able to monitor and express concerns about their well-being than adults.

Adolescent↗