Pharmacotherapy In Children Research Articles

Contemporary assessment and pharmacotherapy of Tourette syndrome

To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention—deficit/hyperactivity disorder (ADHD) and obsessive—compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

Contemporary Assessment and Pharmacotherapy of Tourette Syndrome

To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

Children with Schizophrenia

Awareness of childhood-onset schizophrenia is rapidly increasing, with a more precise definition now available of the clinical picture and early signs, the outcome and the treatment strategies. Premorbid developmental impairments, including language, motor and social deficits, are more frequent and more pronounced in earlier- than in later-onset forms of schizophrenia. This 'pan-dysmaturation' is reported from the first months of life in more than half of the children who will develop childhood-onset schizophrenia, and it suggests a more severe and early disruption of brain development compared with the adolescent- and adult-onset disorder. The insidious onset in at least 75% of children, the high rates of premorbid problems and the hesitancy on the part of clinicians to make a diagnosis of schizophrenia in a child usually delay the recognition of the syndrome. Elementary auditory hallucinations are the most frequent positive symptom, while visual and tactile hallucinations are rarer. Delusions are less complex than in adolescents and are usually related to childhood themes. Negative symptoms are largely predominant, namely flat or inappropriate affect. A marked deterioration from the previous level of functioning is present in all these children, and an impaired outcome is reported in approximately 50-60% of them. The main diagnostic challenges are with differentiating childhood-onset schizophrenia from affective disorders (both depression and bipolar disorder) with psychotic symptoms, pervasive developmental disorders and severe personality disorders. Post-traumatic stress disorder and obsessive-compulsive disorder without insight may also be misdiagnosed as schizophrenia. Furthermore, approximately 10% of children from the community report nonpsychotic hallucinations or delusions. Finally, children with atypical psychotic features that do not strictly fit diagnostic criteria for schizophrenia have been described, and new labels have been proposed to categorise these clinical patterns, such as multidimensionally impaired disorder and multiple complex developmental disorder. In the context of a multimodal approach, including behavioral, social, scholastic and familial interventions, a pharmacological treatment is usually the core treatment. Available experience from the few controlled studies, open studies and case reports on pharmacotherapy in children with schizophrenia aged <12 years is critically analysed in this review, with particular reference to the use of atypical antipsychotics in clinical practice. To date, the major evidence supports the efficacy of risperidone and olanzapine, while clozapine seems an effective option in treatment-refractory cases. Published experience with newer atypical antipsychotics (quetiapine, ziprasidone, aripiprazole) is still lacking in this age range. Safety data (namely extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant syndrome and cardiovascular effects) are reviewed and discussed, along with strategies for management.

Sequential Pharmacotherapy for Children With Comorbid Attention-Deficit/Hyperactivity and Anxiety Disorders

Sequential Pharmacotherapy for Children With Comorbid Attention-Deficit/Hyperactivity and Anxiety Disorders

A Naturalistic Study of Referred Children and Adolescents With Obsessive-Compulsive Disorder

To report on clinical features, comorbidity, and response to pharmacotherapy in children and adolescents with obsessive-compulsive disorder (OCD) naturalistically followed and treated with serotonin reuptake inhibitors (SRIs). A consecutive series of 94 patients (65 males, 29 females, age 13.6 +/- 2.8 years), referred in the period January 2001-April 2004, diagnosed with a clinical interview (Diagnostic Interview for Children and Adolescents-Revised), and followed for 10 +/- 6 months, were included in the study. Contamination obsessions and washing rituals were associated with less impairment than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as well as symmetry obsessions and ordering-repeating rituals were more frequently comorbid with tic disorders. According to the Clinical Global Impressions-Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment. Nonresponders were more severely impaired and had a higher number of comorbid disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed other medications. Patients receiving SRI monotherapy were less severely impaired; had a later onset of OCD; were at a younger age at the visit, had higher rates of depression and anxiety and lower rates of bipolar disorder, attention-deficit/hyperactivity disorder, and conduct disorder (p < .05). Long-term naturalistic prospective studies in pediatric patients with OCD might represent an important source of information for everyday care regarding the effectiveness of a treatment over extended periods of time under routine clinical conditions.

Concomitant Pharmacotherapy among Youths Treated in Routine Psychiatric Practice

The aim of this study was to assess rates and correlates of concomitant pharmacotherapy in children and adolescents treated by psychiatrists in a broad range of clinical settings. Cross-sectional data on 392 child and adolescent patients aged 2-17 years from the 1997 and 1999 American Psychiatric Practice Research Network Study of Psychiatric Patients and Treatments were used, and weighted estimates are provided. Findings indicate that 84% of child and adolescent patients received one or more psychopharmacologic medications; 52% of patients treated with medications received concomitant pharmacotherapy (i.e., two or more medications). Patients who were treated with psychopharmacologic treatments received a median of 2 medications (range, 1-6). Highest rates of concomitant pharmacotherapy were among patients with bipolar disorder (87%). Correlates of concomitant pharmacotherapy included: (1) having a diagnosis of bipolar disorder, (2) having co-occurring Axis I or II disorders or general medical conditions, and (3) currently receiving treatment in an inpatient setting. Over 40% of child and adolescent patients of psychiatrists were prescribed two or more psychopharmacologic medications. Patients with chronic and clinically complex conditions were more likely to receive concomitant pharmacotherapy. Most often, efficacy of U.S. Food and Drug Administration (FDA)-approved medications has been examined as monotherapy, and cautions on drug interactions and off-label use derived from multiple sources accompany each product. With high rates of concomitant pharmacotherapy among children and adolescents in psychiatric care, additional research on efficacy and safety of this treatment strategy is necessary.

US Physician Adherence to Standards in Asthma Pharmacotherapy Varies by Patient and Physician Characteristics

US Physician Adherence to Standards in Asthma Pharmacotherapy Varies by Patient and Physician Characteristics

Combination pharmacotherapy in children and adolescents with bipolar disorder

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

Drug therapy for adults with attention-deficit hyperactivity disorder.

Practitioners are increasingly called upon to diagnose and treat attention deficit hyperactivity disorder (ADHD) in adults. Although the use of pharmacotherapy in children with ADHD is well studied, the use of drugs for the treatment of adults with ADHD remains less well established.A systematic review of the literature identified 15 studies (n = 482 patients) of stimulants, and 27 studies of nonstimulant medications (n = 1179 subjects) including antidepressants, norepinephrine reuptake inhibitors, antihypertensive agents, amino acids and wake-promoting agents for the treatment of ADHD in adults. Controlled clinical trials in adults showed that stimulants, antidepressants and norepinephrine reuptake inhibitors demonstrated significant short-term improvements in ADHD symptoms compared with placebo. The two longer term trials with methylphenidate in adults confirmed the ongoing effectiveness and tolerability of stimulants. The response to amphetamine and methylphenidate appears to be dose-dependent. Methylphenidate and amphetamine had an immediate onset of action, whereas responses to pemoline, antidepressants and norepinephrine reuptake inhibitors appeared delayed. Controlled data on nicotinic/cholinergic compounds appear promising. Considerable variability was found in the diagnostic criteria for ADHD in adults, drug dosages and response rates between the various studies. Under controlled conditions, the aggregate literature comprised mainly of short-term studies, shows that stimulants, norepinephrine reuptake inhibitors and specific antidepressants had clinically and statistically significant beneficial effects in the treatment of ADHD in adults. Cholinergic agents appear promising. Further studies are necessary to evaluate the long-term effectiveness and tolerability of various agents, functional and neuropsychological outcomes, and the use of various agents in specific subgroups of adults with ADHD.

The effects of acute antipsychotic drug administration on the neurotensin system of the developing rat brain

The effects of antipsychotic drugs on the neurotensin (NT) system have been well characterized in adult male animals. There is considerable evidence that the NT system undergoes distinct age-related changes during development of the rat brain. This observation in conjunction with antipsychotic pharmacotherapy in children and breast feeding women led us to characterize the effects of antipsychotic drug administration in neonatal rats. The effects of a single subcutaneous injection of haloperidol (2.0 mg/kg) on the developing NT system were determined between postnatal days 10 and 21. Haloperidol significantly increased NT/neuromedin N (NT/NN) mRNA expression and NT concentrations in the caudate/putamen as early as postnatal day 10. Haloperidol did not increase NT/NN mRNA expression in the nucleus accumbens until postnatal day 15 and did not increase NT concentrations in this brain region until postnatal day 21. These results demonstrate that there is a critical time point in development before which the NT system does not respond to antipsychotic drug administration in the same manner as the mature rat.

Handbook of Child and Adolescent Outpatient, Day Treatment, and Community Psychiatry

Handbook of Child and Adolescent Outpatient, Day Treatment, and Community Psychiatry

Pharmacotherapy of disorders in mental retardation.

This is a review of pharmacotherapy in children and adolescents with mental retardation from the perspective of DSM and ICD disorders. The existing research is reviewed in young people with mental retardation but, when data are lacking, we examined the literature from adults with mental retardation and from typically-developing children. The literature is discussed for each of the following disorders: ADHD, anxiety disorders, bipolar disorder, conduct disorder, depression, enuresis, schizophrenia, self injury, and tics and movement disorders. With the possible exception of ADHD, there is a woeful lack of empirical data on most of these disorders in young people with mental retardation. Clinicians will often be forced to extrapolate from data on adults having mental retardation and from typically-developing children. The best policy is probably to treat such patients cautiously, while gathering data on the effects of such therapy in the hopes of beginning a data base.

Role of lipid-lowering pharmacotherapy in children.

For patients with coronary artery disease and healthy middle-aged or older individuals with elevated cholesterol levels, treatment with cholesterol-lowering drugs reduces morbidity and sometimes mortality. Treatment reverses established atherosclerotic lesions within a relatively short period of time, suggesting that starting cholesterol-lowering drugs in adulthood is adequate for most people at risk. Children with genetic lipid disorders, including familial hypercholesterolaemia and familial combined hyperlipidaemia, may be candidates for earlier therapy. A complete assessment of risk factors should be undertaken to determine which children are at highest risk. Treatment should start with diet, because diet is an important independent protective factor for disease. The bile acid sequestrants (resins) are the only drugs approved for children and may reduce low density lipoprotein (LDL)-cholesterol levels by 15 to 20% at best. Long term tolerability is good, but many children will not take the resins because they find them unpalatable. Tablet formulations have higher acceptability. Some children require supplementation with fat soluble vitamins or folate. Although hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have not been tested in long term studies in children, safety records are excellent in adults. Short term studies show that HMG-CoA reductase inhibitors reduce LDL-cholesterol levels similarly in children and in adults. Thus, the drugs may be used in low dosages to treat some adolescents with exceptional risk of disease.

Role of Lipid-Lowering Pharmacotherapy in Children

Role of Lipid-Lowering Pharmacotherapy in Children

Pharmacotherapy in children and adolescents with pervasive developmental disorders.

Children with autism and the related PDDs may benefit from serotonin reuptake inhibitors such as clomipramine, fluoxetine, fluvoxamine, and sertraline for targeting repetitive thoughts and behaviors, anxiety, and depressed mood. To date, however, there are few controlled studies of these agents in children with PDD, so definitive evidence is lacking. Despite preliminary results in favor of naltrexone, neuroleptic medication appears to be effective for reducing aggression, self-injurious behavior, agitation, and stereotypies. The primary drawback with traditional neuroleptics is risk of short- and long-term side effects. The newer atypical neuroleptics have the potential for benefit with fewer extrapyramidal side effects, but more study is needed to establish their efficacy and safety. Children on neuroleptic medications should be started at the lowest possible dose, with gradual increases until clinical benefit is observed. The likelihood of untoward side effects is increased if the medication dose is increased rapidly. Baseline measurement of target behaviors can be aided by using standardized scales. The presence of abnormal movements should be assessed before initiating treatment and at regular intervals during the course of treatment--including after medication withdrawal. Weight gain is emerging as a recurrent side effect with the atypical neuroleptics. Thus, weight should be monitored, and the family should be advised about a diet baseline. As with all treatments of children with severe behavioral difficulties, pharmacotherapy should be instituted in the context of an integrated treatment plan.

Combined Pharmacotherapy in Children and Adolescents in a Residential Treatment Center

To investigate characteristics of children and adolescents with a history of combined pharmacotherapy (CPT) and compare them with a group with no history of CPT. Eighty-three consecutive admissions to a residential treatment center were divided into a CPT and a no-CPT group based on treatment history and compared by chart review. Prevalence of lifetime psychiatric medication use and CPT exposure were assessed. Demographic, diagnostic, treatment, behavioral, and medication variables were compared across the two groups. Medication use was present in the treatment history for 89.2% and a history of CPT was found for 60.3% of subjects. Admission to current placement from inpatient psychiatry, lifetime number of psychiatric placements, lifetime number of psychiatric diagnoses, and nonseizure neuropsychiatric comorbidity were significantly associated with CPT. Aggression and neuroleptic use were also significantly associated with CPT. Admission psychiatric diagnostic comorbidity was not associated with CPT. A high prevalence of psychiatric medication use and CPT was found in this population. Variables assessing illness severity, aggressive behavior, and nonseizure neuropsychiatric comorbidity may identify youths in psychiatric treatment settings with a high prevalence of past or current CPT exposure. Further research on the CPT of aggression is warranted.

PHARMACOGENETICS IN PEDIATRICS: Implications for Practice

Cumulative experience with pharmacotherapy in children indicates that it is difficult to prescribe medications rationally solely on the basis of patient age. Furthermore, the apparent drug biotransformation phenotype may be influenced by disease (e.g., infection), environmental factors (e.g., diet and environmental contaminants), and concurrent medications. Therefore, characterization of drug biotransformation pathways during development and, at a given developmental stage, the effects of known modulators of drug biotransformation are essential for optimum treatment. This is particularly true when one considers that altered drug biotransformation may contribute significantly to therapeutic failure (e.g., graft rejection with inadequate serum and tissue concentrations of cyclosporin and myelotoxicity consequent to a relative inability to metabolize normal doses of certain antineoplastic agents). Accordingly, the goals of coordinated clinical and basic investigations should be to characterize important drug biotransformation pathways for compounds under development and intended for use in pediatrics and to identify the population extremes or "outliers" to aid in selection of an appropriate dosage range for efficacy studies. Acquired knowledge should then be incorporated into the drug-design process to further maximize the efficacy-toxicity ratio. The development of acceptable, preferably noninvasive, phenotyping procedures for all age ranges including neonates, infants, and older children is a major challenge for investigators but, if met, will be rewarded with improved pediatric pharmacotherapy.

An overview of three decades of research in pediatric psychopharmacoepidemiology.

Although psychotropic drugs are prescribed relatively often for childhood psychiatric and seizure disorders, relatively little is known about their use in everyday clinical settings--with the exception of children with ADHD and individuals with mental retardation. A legion of methodological and logistical obstacles are encountered when trying to gather information about pharmacotherapy for children, and this has often limited data collection to institutional settings or highly restricted geographic areas. Although initial efforts to study the extent of drug therapy focused primarily on the number of individuals receiving treatment and secondarily on drug dose, the breadth of topics quickly expanded to include numerous issues pertaining to the way psychotherapeutic agents are prescribed, evaluated, and monitored in typical clinical situations. This article presents an overview of treatment prevalence studies conducted during the past three decades and reviews a variety of clinical concerns raised by researchers in pediatric psychopharmacoepidemiology. The most salient findings from these studies are: (a) medication use continues to increase, (b) treatment prevalence rates in residential programs continue to be very high (40%-60%), and (c) many researchers continue to be concerned about the quality of treatment practices. The methodologies of this field show considerable promise for addressing pressing issues in health care for children and adolescents with emotional or behavioral disorders.

Attention deficit hyperactivity disorder in adolescent mania

The purpose of this study was to examine the rate of attention deficit hyperactivity disorder in adolescents with bipolar disorder and to explore the potential effects of comorbid attention deficit hyperactivity disorder on the phenomenology of adolescent bipolar disorder. The authors assessed the rate of attention deficit hyperactivity disorder for adolescents with bipolar disorder who were hospitalized for treatment of acute mania or hypomania. Eight (57%) of 14 adolescent bipolar patients also met DSM-III-R criteria for attention deficit hyperactivity disorder. Patients with both disorders were more likely to be male and Caucasian and to have mixed rather than manic bipolar disorder. Patients with attention deficit hyperactivity disorder had a higher mean total score on the Young Mania Rating Scale than patients with bipolar disorder alone. Although preliminary, these findings may have important implications regarding the potential relationship between bipolar disorder and attention deficit hyperactivity disorder.

Primary Care Management of Children with Bronchial Asthma: The Role of Inhaled Glucocorticoids

Studies show that 75% of all asthma-related office visits for patients under the age of 18 are made to primary care clinicians (family practice physicians and/or pediatricians). These caregivers have traditionally been reluctant to employ corticosteroids or inhaled glucocorticoids for pediatric patients, but accepted pharmacotherapy for children now includes the use of inhaled glucocorticoids for moderate to severe asthma. This recommendation has been set by the National Heart, Lung and Blood Institute's Guidelines for the Diagnosis and Management of Asthma, with input from the American Academy of Pediatricians, among others. This paper documents special considerations for pediatric patients with asthma and is designed to help the practitioner reach a correct differential diagnosis and categorization, and to institute appropriate therapy.