Biomedical subjects

B Vitiello

Publications and source records attributed to B Vitiello.

At least 37 records · Page 2Linked to original sources

PubMed2000

Anxiety as a predictor and outcome variable in the multimodal treatment study of children with ADHD (MTA).

Initial moderator analyses in the Multimodal Treatment Study of Children with ADHD (MTA) suggested that child anxiety ascertained by parent report on the Diagnostic Interview Schedule for Children 2.3 (DISC Anxiety) differentially moderated the outcome of treatment. Left unanswered were questions regarding the nature of DISC Anxiety, the impact of comorbid conduct problems on the moderating effect of DISC Anxiety, and the clinical significance of DISC Anxiety as a moderator of treatment outcome. Thirty-three percent of MTA subjects met DSM-III-R criteria for an anxiety disorder excluding simple phobias. Of these, two-thirds also met DSM-III-R criteria for comorbid oppositional-defiant or conduct disorder whereas one-third did not, yielding an odds ratio of approximately two for DISC Anxiety, given conduct problems. In this context, exploratory analyses of baseline data suggest that DISC Anxiety may reflect parental attributions regarding child negative affectivity and associated behavior problems (unlike fearfulness), particularly in the area of social interactions, another core component of anxiety that is more typically associated with phobic symptoms. Analyses using hierarchical linear modeling (HLM) indicate that the moderating effect of DISC Anxiety continues to favor the inclusion of psychosocial treatment for anxious ADHD children irrespective of the presence or absence of comorbid conduct problems. This effect, which is clinically meaningful, is confined primarily to parent-reported outcomes involving disruptive behavior, internalizing symptoms, and inattention; and is generally stronger for combined than unimodal treatment. Contravening earlier studies, no adverse effect of anxiety on medication response for core ADHD or other outcomes in anxious or nonanxious ADHD children was demonstrated. When treating ADHD, it is important to search for comorbid anxiety and negative affectivity and to adjust treatment strategies accordingly.

Anxiety↗

PubMed2000

Family processes and treatment outcome in the MTA: negative/ineffective parenting practices in relation to multimodal treatment.

To elucidate processes underlying therapeutic change in a large-scale randomized clinical trial, we examined whether alterations in self-reported parenting practices were associated with the effects of behavioral, medication, or combination treatments on teacher-reported outcomes (disruptive behavior, social skills, internalizing symptoms) in children with attention-deficit hyperactivity disorder (ADHD). Participants were 579 children with Combined-type ADHD, aged 7-9.9 years, in the Multimodal Treatment Study of Children with ADHD (MTA). We uncovered 2 second-order factors of parenting practices, entitled Positive Involvement and Negative/Ineffective Discipline. Although Positive Involvement was not associated with amelioration of the school-based outcome measures, reductions in Negative/Ineffective Discipline mediated improvement in children's social skills at school. For families showing the greatest reductions in Negative/Ineffective Discipline, effects of combined medication plus behavioral treatment were pronounced in relation to regular community care. Furthermore, only in combination treatment (and not in behavioral treatment alone) was decreased Negative/Ineffective Discipline associated with reduction in children's disruptive behavior at school. Here, children in families receiving combination treatment who showed the greatest reductions in Negative/Ineffective Discipline had teacher-reported disruptive behavior that was essentially normalized. Overall, the success of combination treatment for important school-related outcomes appears related to reductions in negative and ineffective parenting practices at home; we discuss problems in interpreting the temporal sequencing of such process-outcome linkages and the means by which multimodal treatment may be mediated by psychosocial processes related to parenting.

Adult↗

PubMed2000

Familial aggregation of ADHD characteristics.

Patterns of familial aggregation of ADHD symptoms in parents of ADHD and non-ADHD children were examined. Within the ADHD sample, symptom aggregation was examined as a function of biological relationship, parent and child gender, and children's comorbid diagnoses. Participants consisted of parents of 579 children with ADHD, Combined Type participating in the multimodal treatment study of children with ADHD and parents of 288 normal control participants. Adult symptoms of ADHD were measured by both self-report and report of a significant other. Results indicated that the parents of children with ADHD had higher ratings of inattention/cognitive problems, hyperactivity/restlessness, impulsivity/emotional lability, and lower self-concept than parents of children without ADHD on both self-report and other-report ratings. Within the ADHD sample of children, other-report ratings of inattention/cognitive problems and impulsivity/emotional lability were higher for biological parents compared to nonbiological parents whereas self-ratings were not related to biological status. These findings support previous research documenting familial aggregation of ADHD and appear to strengthen the hypothesis that there is a genetic contribution to ADHD.

Adult↗

PubMed2000

Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology.

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

Antipsychotic Agents↗

PubMed2000

Medication management of stimulants in pediatric practice settings: a national perspective.

Using a nationally representative sample of office-based physicians, the management practices of pediatricians, psychiatrists, and family practice physicians were investigated. The major aims were to determine (1) what types of services these physicians were providing to children who received stimulants, (2) what factors predicted receipt of stimulants, and (3) whether these practices were concordant or discordant with professional consensus on diagnosis and treatment of attention-deficit hyperactivity disorders (ADHD). Prescribing and management practice data from the 1995 National Ambulatory Medical Care Survey (NAMCS) were analyzed for children ages 0 to 17 years who were seen for psychiatric problems and received stimulant medication. Results indicated that 2 million visits by children were made in 1995 to psychiatrists, pediatricians, or family practitioners in which psychotropic medications were prescribed. In pediatric visits where stimulant medication was prescribed, mental health counseling was provided 47.3% of the time and psychotherapy 21.6%. Follow-up arrangements were made in 79.1% of the visits. Psychiatrists were significantly more likely to provide psychotherapy and to specify follow-up visits than were pediatricians, but less likely to provide other health counseling. Controlling for demographic and physician effects, the factors with the most significant effect on the probability of receiving stimulants were geographic region (living in the South), race (being white), receiving mental health counseling, not receiving psychotherapy, and having health insurance. Less than 50% of pediatric visits for psychiatric reasons involving stimulant medications included any form of psychosocial intervention. In 21% of these visits, no recommendations were made for follow-up care. These practices diverge from National Institutes of Health (NIH) consensus panel recommendations and association-issued practice parameters.

Adolescent↗

PubMed2000

Impact of psychiatric conditions on health-related quality of life in persons with HIV infection.

OBJECTIVE: Little is known about the impact of comorbid psychiatric symptoms in persons with HIV. This study estimates the burden on health-related quality of life associated with comorbid psychiatric conditions in a nationally representative sample of persons with HIV. METHOD: The authors conducted a multistage sampling of urban and rural areas to produce a national probability sample of persons with HIV receiving medical care in the contiguous United States (N=2,864). Subjects were screened for psychiatric conditions with the short form of the Composite International Diagnostic Interview. Heavy drinking was assessed on the basis of quantity and frequency of drinking. Health-related quality of life was rated with a 28-item instrument adapted from similar measures used in the Medical Outcomes Study. RESULTS: HIV subjects with a probable mood disorder diagnosis had significantly lower scores on health-related quality of life measures than did those without such symptoms. Diminished health-related quality of life was not associated with heavy drinking, and in drug users it was accounted for by presence of a comorbid mood disorder. CONCLUSIONS: Optimization of health-related quality of life is particularly important now that HIV is a chronic disease with the prospect of long-term survival. Comorbid psychiatric conditions may serve as markers for impaired functioning and well-being in persons with HIV. Inclusion of sufficient numbers of appropriately trained mental health professionals to identify and treat such conditions may reduce unnecessary utilization of other health services and improve health-related quality of life in persons with HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Adolescent↗

PubMed1999

Integrating science and ethics in child and adolescent psychiatry research.

Research to elucidate the biological bases of psychopathology in children and adolescents is needed to understand pathogenesis and to develop effective and safe treatment and preventive interventions. Because of the effect of development, data collected in adults are not always applicable to youth, and direct participation of children in research is necessary. Many medications are currently used in the community to treat children and adolescents with neuropsychiatric disorders without adequate data about their safety and efficacy. Conducting research in children requires attention to specific ethical and regulatory factors. In deciding whether minors can participate in a study with potential direct benefit to the research subjects, the most important variable to consider is the balance between risks and potential benefit, in the context of the severity of the child's condition and the available alternatives. Research with no potential benefit to the participants is guided by the concepts of minimal risk (which may apply more to normal children) and minor increase over minimal risk (perhaps more relevant to children affected by psychopathology). Recently conducted studies relevant to this issue are reviewed. Of paramount importance is the ratio of risk/scientific value of the proposed experiment. In fact, no research is justifiable, no matter how low the risk may be, unless the potential yield of the study is important and may help advance our understanding of normal functioning and mental illness.

Adolescent↗

PubMed1999

Psychoactive medication prescribing practices for U.S. children: gaps between research and clinical practice.

OBJECTIVE: To determine national pediatric prescribing practices for psychotropic agents and to examine these practices in view of the available evidence concerning their safety and efficacy in this age group. METHOD: Prescribing data from 2 national databases based on surveys of office-based medical practices were determined and reviewed vis-à-vis available safety and efficacy evidence. RESULTS: Data indicate that levels of psychotropic prescribing in children and adolescents are greatest for stimulants, resulting in nearly 2 million office visits and 6 million drug "mentions" in 1995. Selective serotonin reuptake inhibitors were the second most prescribed psychotropic agents, while anticonvulsant mood stabilizers (prescribed for a psychiatric reason), tricyclic antidepressants, central adrenergic agonists, antipsychotics, benzodiazepines, and lithium were also prescribed for a substantial number of office visits. Comparison of prescribing frequencies with available safety and efficacy data indicates significant gaps in knowledge for commonly used agents. CONCLUSIONS: Most psychotropic agents require further sustained study to ensure appropriate health care expenditures and vouchsafe children's safety. Recommendations for researchers, parents, federal agencies, and industry are offered as a means to accelerate the pace of research progress.

Adolescent↗

PubMed1999

Hypericum perforatum extracts as potential antidepressants.

Extracts of Hypericum perforatum have been used in the treatment of mild to moderate depression for many years in Europe. More recently, these extracts have become available in the USA as dietary supplements and have been popularly used to improve mood. In support of this practice, data from several controlled clinical studies suggest that Hypericum perforatum is better than placebo and as effective as established antidepressant drugs. These data have, however, several limitations that should temper our enthusiasm and argue for more research before accepting Hypericum perforatum extracts into our pharmacopoeia of established antidepressants. Extant data on the possible effects of Hypericum perforatum extracts in depression are here critically reviewed and plans for further research presented.

Antidepressive Agents↗

PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗

PubMed1998

Pediatric psychopharmacology and the interaction between drugs and the developing brain.

With increasing frequency, psychotropic medications are being prescribed to young children, often for long periods of time. The interaction between psychotropics and the developing brain has not been systematically investigated in humans. Data collected from animals suggest that developing neurotransmitter systems can be exquisitely sensitive to early inhibition or stimulation by pharmacological agents, which can lead to permanent changes in adult life. Most of these data are collected from rodents, and their extrapolation to humans is difficult. More relevant models could be developed for instance using primates. In humans, the focus of research has traditionally been on the possible teratogenic effects of prenatal drug exposure. Recently introduced quantitative imaging techniques can offer new approaches to studying the effects of psychotropics on the developing brain. This research has clear implications for the safety and efficacy of psychopharmacologic drug in children.

Age Factors↗

PubMed1997

Medication development and testing in children and adolescents. Current problems, future directions.

Progress in pediatric psychopharmacological research has suffered notable delay, especially compared with the achievements in adult psychopharmacology. Although safety and efficacy of the use of many psychotropic agents in children remain largely unproved, their pediatric use has been increasing and their widespread off-label prescribing by practitioners has raised some important concerns. The National Institute of Mental Health, in cooperation with the Food and Drug Administration and leading researchers, has coordinated systematic efforts to identify the major obstacles to research in pediatric psychopharmacology and to propose feasible solutions. In 1995, a conference cosponsored by the national Institute of Mental Health and the Food and Drug Administration gathered more than 100 research experts, family and patient advocates, and representatives of mental health professional associations. Participants met in working groups focused on specific aspects of child research and reached consensus on various recommendations. Each of the various aspects relevant to conducting research in this area (methodological, ethical, legal, regulatory, financial, and family or community context) presents specific challenges, which are herein outlined. Recommendations for possible solutions are presented, some of which are being implemented. Because data about drug safety and efficacy in adults can rarely be extrapolated to children, there is no substitute for pediatric psychopharmacological research. Successful strategies for overcoming the many obstacles with which this research has to contend must enlist the concerted efforts of all the relevant parties (investigators, clinicians, industry, federal agencies, ethicists, families, and community representatives).

Adolescent↗

PubMed1997

Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans.

The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind, randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg p.o.) +/-scopolamine (0.5 mg i.v.), metergoline (4 mg p.o.) +/-scopolamine (0.5 mg i.v.), placebo, and scopolamine alone (0.5 mg i.v.)]. Scopolamine-induced sedation (p < .01), slowed information processing (p < .01) and impaired new learning and memory (p < .01), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitive sets (p < .05), and metergoline decreased pupil size (p < .01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p < .10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade.

Adult↗

PubMed1997

Pediatric pharmacoepidemiology: clinical applications and research priorities in children's mental health.

Explore the source record for details and available documents.

Adolescent↗

PubMed1997

Treatment algorithms in child psychopharmacology research.

Clinical trials in child psychiatry research have increased in complexity. Several factors have contributed to this change, including the need to compare multiple therapies, to re-create clinically relevant situations in research, to standardize treatment approaches, to account for the impact of comorbidity, to respond to the needs of individual patients, and to optimize treatment accordingly. To preserve the clinical and internal validity of the experimental interventions vis-à-vis their increasing complexity, researchers have started developing treatment algorithms. These deductive systems for handling data allow us to standardize and incorporate clinical judgment into study designs through the adoption of a stepwise decision making process. Treatment algorithms are different from treatment guidelines. Guidelines are general recommendations that apply to groups of patients with certain characteristics; they are not fully detailed and are created with the expectation that clinical judgment will be applied in individual cases. Algorithms are patient specific, are intended to capture all the relevant details of the clinical situation, and require minimal clinical judgment for their clinical application; they are designed to minimize the role of clinical judgment in research protocols. The entire multistep algorithm is tested in a clinical trial, not the single steps that constitute the algorithm, so proving the efficacy of an algorithm cannot replace a controlled assessment of the individual treatments embedded in the algorithm. Some characteristics, properties, and limitations of algorithms in child psychiatry and psychopharmacology research are presented along with two examples of algorithms currently used in child and adolescent psychopharmacology. Although treatment algorithms seldom have been used in pediatric psychiatry and psychopharmacology, there are indications that their use will increase in the near future and will allow the standardized introduction of clinical judgment into research design.

Adolescent↗

PubMed1997

Subtypes of aggression and their relevance to child psychiatry.

OBJECTIVE: To review the evidence for qualitatively distinct subtypes of human aggression as they relate to childhood psychopathology. METHOD: Critical review of the pertinent literature. RESULTS: In humans, as well as in animals, the term aggression encompasses a variety of behaviors that are heterogeneous for clinical phenomenology and neurobiological features. No simple extrapolation of animal subtypes to humans is possible, mainly because of the impact of complex cultural variables on behavior. On the whole, research into subtypes of human aggression has been rather limited. A significant part of it has been conducted in children. Clinical observation, experimental paradigms in the laboratory, and cluster/factor-analytic statistics have all been used in an attempt to subdivide aggression. A consistent dichotomy can be identified between an impulsive-reactive-hostile-affective subtype and a controlled-proactive-instrumental-predatory subtype. Although good internal consistency and partial descriptive validity have been shown, these constructs still need full external validation, especially regarding their predicting power of comorbidity, treatment response, and long-term prognosis. CONCLUSIONS: Our understanding and treatment of children and adolescents with aggressive behavior can benefit from research on subtypes of aggression. The differentiation between the impulsive-affective and controlled-predatory subtype as qualitatively different forms of aggressive behavior has emerged as the most promising construct. Specific therapeutic hypotheses could be tested in this context and contribute to a full validation of these concepts.

Adolescent↗

PubMed1997

Toward clinically relevant clinical trials.

This article grapples with two closely related tensions threatening the credibility and relevance of clinical trials to clinicians as well as patients and their families: (1) the tension between clinical flexibility and scientific standardization of protocol and (2) the tension between the need to ensure scientific integrity through a standard, pre-specified protocol and the need to increase compliance by involving patients and their families in goal setting and treatment planning. We propose four partial solutions: (1) relaxed exclusion criteria to maximize generalizability, using only those exclusion criteria essential to the treatment; (2) extensive use of clinical algorithms to incorporate clinical flexibility in a standardized way; (3) active involvement of therapists in decision-making, including cross-site clinical decision panels; and (4) active involvement of families through a goal-setting and treatment-planning session as the first step of treatment. Although we focus on clinical trials with children and adolescents, the principles and ideas may also apply to clinical trials with patients of any age. This article summarizes and elaborates on presentations made by three of the authors at workshops on psychiatric clinical trials in children and adolescents at the May 1996 New Clinical Drug Evaluation Unit (NCDEU) meeting. The focus was on enhancing the clinical relevance of clinical trials-making the results useful and credible to practitioners and patients and their families.

Adolescent↗