Frusemide inhibits angiotensin II-induced contraction on human vascular smooth muscle

OBJECTIVE: To provide an overview of the use of psychotropic drugs in preschoolers. METHOD: Literature review. RESULTS: Although controversy persists, the evidence suggests that preschool children are being given an increasing number of psychotropic drugs, especially by general practitioners and pediatricians. CONCLUSION: There is an urgent need to formally evaluate the efficacy of psychotropic medication for young children.     

Psychopharmacology of aggression in children and adolescents with primary neuropsychiatric disorders: A review of current and potentially promising treatment options.

Research examining the role of pharmacological therapy in the treatment of children and adolescents with clinical disorders is growing. Clinical disorders that present with comorbid aggression can add a challenge to treatment. Child and adolescent neuropsychiatric disorders associated with aggression include attention-deficit hyperactivity disorder, various mood disorders and in particular bipolar disorders/pediatric mania, schizophrenia, mental retardation, oppositional defiant disorder, conduct disorder, and autism spectrum disorders. This review describes the psychopharmacy to treat these disorders and the aggression that often appears comorbidly. Existing literature regarding the efficacy and safety of psychotropics for youth with neuropsychiatric disorders also is discussed. In addition, general guidelines for psychopharmacy of aggression in children and adolescents are presented. Studies reviewed in this article provide evidence for the use of psychostimulants, alpha-2 agonists, beta blockers, lithium, anticonvulsant mood-stabilizers, atypical antipsychotics, traditional antipsychotics, and selective serotonin reuptake inhibitors in treating pediatric aggression with the choice of medication dependent on symptomology. Despite increased support for pediatric psychotropic use, there is a need for more long-term safety and efficacy studies of existing medications and newer, safer, and more effective agents with fewer side effects for the pharmacological treatment of all childhood disorders in which aggression is prominent. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recent Advances in Pharmacotherapies for the Externalizing Disorders.

This article provides a review of various psychotropic agents employed for children and adolescents with externalizing disorders. With the exception of the stimulants, clinical use of psychotropic medications for children with externalizing disorders far exceeds the available empirical literature. Further, there are insufficient data pertaining to the safety and efficacy of most psychotropics. Studies that examine the combination of psychotherapy and pharmacotherapy are also reviewed, with particular attention to the National Institutes of Health Multimodal Treatment Study for Children with Attention-Deficit/Hyperactivity Disorder. Recommendations are made for future multimodal studies all externalizing disorders and with all psychotropics in addition to the stimulants. Future goals for research over the next decade include studies that examine treatment acceptability, adherence and satisfaction, adherence with various psychotropic agents, and ecologically valid investigations of pharmacotherapies for both symptom reduction and enhancement of functional behaviors among children and adolescents with externalizing behavioral problems. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Ethical and pragmatic issues in the use of psychotropic agents in young children

OBJECTIVE: To provide an overview of the knowledge base concerning the prescribing of psychotropic agents in young children with mental disorder and related mental health problems. METHOD: Relevant information is reviewed concerning the knowledge base available to inform pediatric psychopharmacology prescribing practices. RESULTS: Very few psychoactive medications have been adequately tested for safety and efficacy in young children, despite relatively high rates of prescribing. CONCLUSION: Behavioral and psychotherapeutic strategies are often the wisest first therapeutic intervention for this age group. Psychotropic medications may be required, but should be used cautiously in young children, while additional studies are being conducted.     

Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle

OBJECTIVE: To evaluate the scope of the available therapeutic armamentarium in attention-deficit hyperactivity disorder (ADHD). METHOD: The literature of medication trials in ADHD was systematically reviewed, with attention to issues of psychiatric comorbidity, age, gender, and ethnic background. RESULTS: One hundred fifty-five controlled studies of 5,768 children, adolescents, and adults have documented the efficacy of stimulants in an estimated 70% of subjects. The literature clearly documents that stimulants not only improve abnormal behaviors of ADHD, but also self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbid conditions. In addition, there is an impressive body of literature documenting the efficacy of tricyclic antidepressants on ADHD in more than 1,000 subjects. Studies of alternative antidepressants, antipsychotics, antihypertensives, and other compounds were also reviewed. CONCLUSIONS: The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-age Caucasian boys. In addition, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.     

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. OBJECTIVE: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. RESULTS: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. CONCLUSIONS: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.     

Pharmacotherapy in Autism and Related Disorders.

Autistic disorder is characterized by qualitative impairment in the areas of social interaction and communication, as well as stereotypic, repetitive patterns of behavior. In addition to the core features of autism, many individuals display a range of behavioral concerns including anxiety, aggression, agitation, overactivity, self-injury, and stereotypic behavior. Recent prevalence estimates indicate that over 45% of individuals with autism are prescribed psychotropic medications for management of associated behavioral disorders. Yet, there remain considerable gaps in our knowledge of medication efficacy and safety in this population. This article provides an overview of the research in this area, including efficacy and potential side effects of the most commonly prescribed psychotropic medications for children and adolescents with autism. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Use of atypical neuroleptics in child and adolescent psychiatry

BACKGROUND: This article reviews the published clinical experience with atypical neuroleptics in children and adolescents. METHOD: A computerized literature search was conducted (MEDLINE, 1974-1998) to retrieve all reports on the use of atypical neuroleptics in children and adolescents. A hand search was performed as well. All relevant clinical data were collated by type of drug. RESULTS: We found 5 blind placebo-controlled clinical trials (105 patients), 24 open-label clinical trials (387 patients), and 33 case series (115 patients) describing the use of the atypical neuroleptics clozapine, risperidone, olanzapine, sulpiride, tiapride, amisulpride, remoxipride, and clothiapine in children and adolescents. Some of these agents, especially clozapine, risperidone, and olanzapine, were found to be efficacious in the treatment of schizophrenia, bipolar disorders, and pervasive developmental disorders. The role of atypical neuroleptics as augmenters of serotonin reuptake inhibitors in obsessive-compulsive disorder is unclear. Risperidone appears to possess anti-tic properties in patients with Tourette's disorder. CONCLUSION: The most convincing evidence of the efficacy of atypical neuroleptics in children and adolescents concerns clozapine in the treatment of schizophrenia. Data on other atypical neuroleptics in other disorders are still sparse, and further research is needed. Some of the atypical neuroleptics may become the first-line treatment for childhood schizophrenia and pervasive developmental disorders.     

Informativeness of child and parent reports on substance use disorders in a sample of ADHD probands, control probands, and their siblings

OBJECTIVE: To evaluate parent-child agreement on psychoactive substance use disorder (PSUD) reporting among children with attention-deficit hyperactivity disorder (ADHD) and to test whether agreement level could be predicted from measures of parent and child psychopathology and substance use severity. METHOD: The authors examined 348 pairs of child and parent assessments in a sample of 108 ADHD and 68 normal control probands and their 172 siblings aged 12 and older. RESULTS: PSUD rates were higher when the child was the reporter than when the parent was. Agreement between parent and child reports was strongest for cigarette smoking, alcohol dependence, and any PSUD. Although parental reports were frequently endorsed by the child's report, the reverse was rarely true. Predictors of parental awareness of the child's PSUD included impaired social functioning, younger age of the child, presence of multiple substance use disorders in the child, and comorbid bipolar disorder. CONCLUSIONS: PSUD rates vary by informant and are higher when the child is the reporter. Because severity of PSUD and multiple substance use were the strongest predictors of parental awareness, more efforts are needed to identify the more covert and milder cases of PSUD that may not reach clinical attention.     

Two-stage urethra-plasty

This article reviews special considerations for children with psychiatric conditions when they present with pediatric emergencies. The review spans a variety of scientific disciplines and attempts to integrate information that is not usually available to the emergency practitioner from a single source; the intent is not to be exhaustive on any particular topic but to organize what is most relevant to pediatric emergency care. Topics that are discussed include: 1) a brief review of true psychiatric emergencies, 2) side effects of psychotropic medications that have direct implications for emergency assessment and management, 3) neurologic disorders that present with psychiatric manifestations, and 4) psychiatric disorders that present with somatic manifestations.     

The contribution of health promotion to community children''s nursing

In the past, a pre-electroconvulsive therapy (ECT) psychiatric evaluation focused on the question, "Does the patient have an ECT-responsive condition?" Technological advances, a broadening experience base with psychiatric patients with concomitant severe medical illness, and advances in ECT technique have led to the need for a more extensive pre-ECT assessment of the patient's psychiatric and medical status, including concomitant medications. A specific "ECT consultation" has evolved that builds on the basic components of the standard psychiatric consultation and extends to recommendations designed to maximize the safety and efficacy of ECT for each individual patient. This article briefly reviews the key components of the ECT consultation and provides an extensive update on important considerations in the use of combined ECT and psychotropic medications.     

Children's Understanding of the Transmission of Genetic Disorders and Contagious Illnesses.

The authors conducted 4 studies suggesting that children attribute different modes of transmission to genetic disorders and contagious illnesses. Study 1 presented preschoolers through 5th graders and adults with "switched-at-birth" scenarios for various disorders. Study 2 presented preschoolers with the same disorders but used contagion links in a contagion context. Studies 3 and 4 presented preschoolers and adults with novel (fictitious) illnesses to determine which cues participants would use to differentiate the modes of transmission. In the presence of kinship cues, children distinguished genetic disorders from contagious illnesses, but in the presence of contagion cues, preschoolers selectively applied contagious links primarily to contagious illnesses. With novel illnesses, preschoolers and adults inferred that permanent illnesses were more likely to be transmitted by birth parents than by contagion. These results suggest that by the preschool years, children recognize that not all disorders are transmitted exclusively through germ contagion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suppression of human fibrosarcoma cell growth by transcription factor, Egr-1, involves down-regulation of Bcl-2

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD), a common psychiatric condition, may impair a child's ability to learn and to form social relationships, tasks critical to healthy development. This study describes the prevalence of the disorder among children in special education programs and identifies the extent and predictors of unmet service needs. METHODS: A 2-stage screening protocol of a countywide population of second- through fourth-grade students in special education was conducted to (1) screen for ADHD, employing standardized parent and teacher questionnaires, and determine health services use (n = 499) and (2) perform diagnostic assessments of ADHD (n = 318). RESULTS: Almost half of the children qualified for a diagnosis of ADHD, yet only half of those were reportedly receiving care for the condition, mainly in the general health care sector. Girls were more than 3 times as likely as boys to have unmet service needs; minority status, low income, and health maintenance organization coverage also emerged as possible risk factors for unmet service needs. CONCLUSIONS: ADHD is a common yet often untreated condition among children in special education. Mental health services for children with this disorder should be integrated with general health care and special education programs.     

The use of tricyclic antidepressants in children and adolescents

For children and adolescents, TCAs have proven efficacy in the treatment of enuresis, OCD, and ADHD, with less compelling evidence in anxiety and tic disorders and as-yet unproven efficacy in major depression. The TCAs continue to be a valuable second-line treatment in the previously mentioned conditions. Given the possible adverse effects caused by these medications and the individual variability in plasma levels, effective, responsible use of these medications includes careful monitoring by the prescribing clinician.     

Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders

We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.     

Validity of DSM-IV attention-deficit/hyperactivity disorder for younger children

OBJECTIVE: Little is known about the validity of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in young children. Moreover, the results of the DSM-IV field trials raised concerns that inclusion of the new predominantly hyperactive-impulsive type of ADHD in DSM-IV might increase the likelihood of the diagnosis being given to active but unimpaired preschool and primary school children. METHOD: The validity of DSM-IV criteria for each subtype of ADHD was evaluated in 126 children, aged 4 through 6 years, and 126 matched comparison children. Probands and controls were classified by using structured diagnostic interviews of the parent and a DSM-IV checklist completed by the teacher. RESULTS: Children who met DSM-IV criteria for each subtype of ADHD according to parent and teacher reports differed consistently from controls on a wide range of measures of social and academic impairment, even when other types of psychopathology and other potential confounds were controlled. CONCLUSIONS: When diagnosed by means of a structured diagnostic protocol, all three DSM-IV subtypes of ADHD are valid for 4- through 6-year-old children in the sense of identifying children with lower mean scores on measures of adaptive functioning that are independently associated with ADHD.     

Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines

OBJECTIVE: Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. METHOD: A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. RESULTS: Three primary effects are associated with medication use during pregnancy: 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. CONCLUSION: Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.     

Preventing discrimination against volunteers in prophylactic HIV vaccine trials: lessons from a phase II trial

OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.     

Conduct disorder with and without mania in a referred sample of ADHD children

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.