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Recent efforts to stimulate research in pediatric psychopharmacology have resulted in increased interest in the effects of psychotropic medications in children and adolescents. This interest is reflected in the number of studies that have been reported or initiated during the past year. As a means of providing a brief update on the progress of child psychopharmacology, research reports either published or presented at national meetings in 1999 are selectively reviewed here. Relevant initiatives recently started under the sponsorship of the National Institute of Mental Health (NIMH) are also reviewed. Most studies have been directed at testing treatments of attention deficit hyperactivity disorder (ADHD), but also studies of the selective serotonin reuptake inhibitors in patients with obsessive compulsive disorder, depression, and anxiety disorders are well represented. The efforts of NIMH to focus on effectiveness research and direct comparisons of pharmacologic, psychosocial, and combined treatment modalities are apparent in recent initiatives in ADHD and depression. Research of treatments for youths with bipolar disorder, schizophrenia, autism, and eating disorders is still scanty and in urgent need of expansion.
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PMID:Current research highlights in child and adolescent psychopharmacology. 1112 42

Stimulants are a key element in the treatment of ADHD. Carefully designed trials of stimulants have found substantial improvement in ADHD core behaviours in 65-75 % of subjects with ADHD. Most standard stimulants are rapidly absorbed, with their behavioural effects appearing within 30 minutes, reaching a peak within one to three hours and disappearing within five hours. Doses at school are often necessary, in spite of the risk of peer ridicule and added adult supervision requirements. The mechanism by which stimulants act to reduce hyperactivity is not completely understood, but they improve impulsivity and activity levels. Several controlled evaluations made over periods of time greater than a year show a clear persistence of medication effects over time. A carefully crafted programme of treatment with methylphenidate is more effective in the reduction of hyperactivity symptoms than an intensive programme of behavioural and cognitive intervention. The combination of stimulants with psychosocial interventions in ADHD offers few advantages over medication alone. Unchallengeable guides to practice that would be appropriate everywhere are difficult to propose. It is imperative that clinicians prescribing stimulants should monitor the use of the drug properly, making sure that it is not being abused by the child's family, peers or those dispensing medication at school. Polypharmacy should only be embarked on by a specialist service and the combination of methylphenidate and clonidine should be used cautiously. Apart from ADHD, stimulants are useful in narcolepsy, resistant depression and partial syndromes of attention and hyperactivity. Major gaps in knowledge remain; pharmacokinetics, pharmacodynamics and pharmacogenetics of stimulant effects need further study. Details of stimulant administration regimes seem to have a major effect on the response achieved. Further research is needed, preferably in realistic practice settings, comparing different forms of combination with psychological interventions, investigating the effects in groups of children outside the core of schoolaged children with typical ADHD: preschool children, adults, those with partial syndromes (such as inattentiveness) and those with co-morbid disorders.
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PMID:Stimulant drugs. 1114 Jul 78

The treatment of the Gilles de la Tourette syndrome has evolved from case reports, clinical experience and more recently blinded trials usually in small numbers of patients. We have reviewed the evidence available to clinicians. The oldest and still most widely prescribed drug, haloperidol, should now not be considered the first-line agent in children as other agents have superior adverse effects profiles. Symptomatic treatment should be targeted to the specific additional psychopathologies seen in the syndrome. For the treatment of tics, sulpiride, tiapride, possibly pimozide and in some cases clonidine may be considered first-line agents. Although a body of data supports pimozide, caution has to be exercised in relation to possible cardiac effects. Antidepressants and stimulants have an important place in the management of depression, obsessionality and attention deficit hyperactivity disorder. The latter also responds to clonidine making it a rational first choice where ADHD coexists with GTS. There are a multitude of other drugs advocated in the literature in addition to reports of neurosurgery and the novel use of immune modulation. Therapeutic trials for GTS are challenging. However, further data from blinded trials are required before many of these treatments can be considered to be mainstream treatment options.
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PMID:Gilles de la Tourette syndrome: symptomatic treatment based on evidence. 1114 Jul 81

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.
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PMID:Pharmacotherapy of disorders in mental retardation. 1114 Jul 85

Clinical trials indicate that inositol may be effective in the treatment of patients with depression, panic disorder and obsessive compulsive disorder (OCD), but not in the treatment of patients with schizophrenia, Alzheimer's disease, ADHD or autism. This spectrum of clinical action parallels that of serotonin selective reuptake inhibitors (SSRIs), but inositol is a precursor in the phosphatidylinositol cycle, a second messenger system distal to the receptor for 5HT-2. To study its mechanism of therapeutic action there is a need to test inositol's activity in animal models of psychopathology. In rats, chronic inositol was demonstrated to increase activity levels, reduce immobility time in the forced swim test and in the reserpine-induced hypoactivity models of depression, and reduce anxiety-like behaviors in the elevated plus-maze. The reduction in anxiety-like behaviors appears to be related to baseline levels of activity. Inositol treatment was not observed to have any effect on amphetamine-induced hyperactivity, apomorphine-induced stereotypy, or on the performance of memory tasks by monkeys. Clinical controlled trials of inositol in patients with depression, panic disorder, and OCD were small, and positive psychoactive effects in animals clearly strengthen the case for further clinical trials and potential for general therapeutic use in humans.
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PMID:The effects of inositol treatment in animal models of psychiatric disorders. 1117 78

Young adults with attention deficit-hyperactivity disorder (ADHD; N = 105) were compared with a control group (N = 64) on 14 measures of executive function and olfactory identification using a 2 (group) X 2 (sex) design. The ADHD group performed significantly worse on 11 measures. No Group X Sex interaction was found on any measures. No differences were found in the ADHD group as a function of ADHD subtype or comorbid oppositional defiant disorder. Comorbid depression influenced the results of only 1 test (Digit Symbol). After IQ was controlled for, some group differences in verbal working memory, attention, and odor identification were no longer significant, whereas those in inhibition, interference control, nonverbal working memory, and other facets of attention remained so. Executive function deficits found in childhood ADHD exist in young adults with ADHD and are largely not influenced by comorbidity but may be partly a function of low intelligence.
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PMID:Executive functioning and olfactory identification in young adults with attention deficit-hyperactivity disorder. 1132 64

Velo-cardio-facial syndrome (VCFS) is a congenital malformation syndrome with variable phenotypic features that has been associated with chromosomal microdeletion 22q11.2. Psychiatric disorders have been reported to be highly prevalent in individuals with this syndrome, and the objective of this study was to assess the nature and extent of psychopathology among individuals with VCFS. We studied 20 children and adolescents with 22q11 deletions determined by fluorescence in situ hybridization (FISH). Control subjects were 11 nondeleted siblings who were the closest age match to the affected subjects. Both affected and control subjects were assessed using two standardized psychiatric research instruments. The results of this study confirmed the high rate of psychiatric disorders among VCFS subjects (60% of our subjects). Of the specific types of disorders, only mood disorders were significantly more common among VCFS subjects compared to sibling controls, with eight VCFS subjects having mood disorders compared with none of the control subjects (P<0.02). Three affected subjects had schizotypal traits comorbid with a mood disorder. In addition, disruptive behavior disorders were frequently diagnosed among VCFS subjects. Using a dimensional measure of psychopathology, significant differences between VCFS subjects and sibling controls were found on three scales: ADHD (P<0.02), separation anxiety (P<0.02), and depression (P<0.01). VCFS subjects were achieving significantly less well academically and requiring significantly more special educational assistance than sibling controls. Follow-up data were available on two subjects, both of whom had been diagnosed with schizophrenia. Further research on psychopathology in VCFS may provide a model of how a specific genetic defect can lead to the development of psychiatric disorders.
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PMID:Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders. 1137 50

Using data based on self-, parent, and teacher reports, we assessed various aspects of psychopathology in a large sample of control children and those with ADHD. Confirmatory factor analysis was employed to extract response bias from latent constructs of aggression, anxiety, attention problems, depression, conduct disorder, and hyperactivity. These latent constructs were then entered into logistic regression equations to predict membership in control versus ADHD groups, and to discriminate between ADHD subtypes. Results of the regression equations showed that higher levels of attention problems and aggression were the best predictors of membership in the ADHD group relative to controls. Logistic regression also indicated that a higher degree of aggression was the only significant predictor of membership in the ADHD-Combined group compared to the ADHD-Inattentive group. However, when comorbid diagnoses of Oppositional Defiant Disorder and Conduct Disorder were controlled for in the logistic regression, greater hyperactivity rather than aggression was the sole variable with which to distinguish the ADHD-Combined from the ADHD-Inattentive subtype. Results are discussed in the context of the DSM-IV ADHD nosology and the role of instrument and source bias in the diagnosis of ADHD.
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PMID:Multimethod assessment of psychopathology among DSM-IV subtypes of children with attention-deficit/hyperactivity disorder: self-, parent, and teacher reports. 1141 82

Between 1988 and 1994, data from 3 large sites revealed a 3-5 fold increase in the prevalence of antidepressant (ATD) treatment for U.S. youths aged 2-19 years. In 1994, the ATD prevalence for youths of this age ranged from 13 per 1000 (in the HMO) to 18 per 1000 (in 2 state Medicaid systems). Males predominated in the 10-14-year-olds treated with ATDs, whereas females predominated among 15-19-year-olds. Caucasians were more than twice as likely to receive ATD therapy than their African-American counterparts. Primary care providers were the major source of ATD prescriptions for youths. The leading diagnoses in primary care were ADHD followed by depression, whereas the diagnostic order was reversed for youths who received psychiatric services. This review provides details concerning these patterns and trends in ATD treatment of youths from community-based clinical data sources. In addition, the role of these data in an expanded, comprehensive psychotropic knowledge base is discussed. Finally, the implications of an expanded knowledge base for ATD treatments are discussed in regard to generating research questions on effectiveness and safety and to improve treatment consensus within a public-health perspective.
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PMID:Services and prevention: pharmacoepidemiology of antidepressant use. 1143 Aug 54

Looking at the field as a whole through metaanalysis, Shadish et al concluded (based on 162 studies) that marital and family therapies were significantly more effective than no treatment and at least as effective as other forms of psychotherapy. Although these reviews and others are positive, individual studies raise many questions. For instance, based on research findings, family treatments increasingly have become standard care for patients with schizophrenia. It remains unclear what degree and type of family involvement is needed for which patients at which stage of their disorder. In the area of anxiety and depression, there are too few studies to make any strong conclusion. Although investigators such as Barrett, Cobham, and Diamond have produced some positive results, the Lewinsohn and Clark studies fail to demonstrate the added benefit of family involvement. Although Brent's study showed CBT to reduce depression faster, family therapy and supportive therapy did just as well in the long run, and family conflict was a strong risk factor for relapse. In the area of anorexia, Russell and Robins produced strong results from family interventions, whereas Geist found no difference between different types of family interventions. Family treatments for obesity have been inconsistent. In a metaanalysis of 41 studies, parental involvement did not contribute significantly to outcomes. In the Epstein study, however, which included 5- and 10-year follow-up, the results of family intervention were impressive. Although many of these studies can be cited for various methodologic flaws, the most consistent problem is that sample sizes are too small to detect difference between two or more active treatments. The most consistent findings (and most well-done, large studies) that support the efficacy of family-based interventions are done with externalizing problems. Work groups led by Patterson, Eisenstadt, Webster-Stratton, Alexander, and Henggeler all have produced impressive reductions of oppositional and antisocial behavior. Clinical programs that treat these populations without using a family-based intervention as at least a component of a treatment package are seriously ignoring the findings of contemporary intervention science. Programs of research by Henggeler, Szapocznik, and Liddle demonstrate similarly impressive results for substance abusing adolescents. Although preliminary results from the Dennis et al study suggest that various treatment approaches may benefit this population. Family interventions have had less success in reducing ADHD symptoms, yet these psychosocial treatments have been essential in reducing much of the family and school behavior problems associated with this disorder. Many investigators would agree that a combined medication and family treatment approach may be the treatment of choice for children with ADHD. In fact, many studies across various disorders suggest that patients respond best to comprehensive treatment packages, of which a family treatment is at least one component. Although the data are promising, many challenges lie ahead. Although collectively many family intervention studies exist, many disorders lack enough rigorous and large-scale investigations to make any strong conclusions. Kazdin argues that sample sizes of 150 are essential to detect significant differences between active treatments, and few of the reviewed studies include these kinds of patient numbers. Furthermore, not enough committed and sophisticated family treatment researchers have carried out some of the major studies. For example, the Brent study on depression and the Barkley study of ADHD, although testing family approaches, lacked well-developed and published treatment manuals, a demonstration of the necessary expertise to supervise these treatments, and data about training and adherence to these models. Although the absence of expertise limits investigator allegiance biases, treatment development and modification are essential for tailoring family treatments to target family processes specific to each disorder. Investigators such as Patterson and Liddle have invested great effort in rigorously dismantling the treatment process, identifying and refining essential ingredients, and repackaging more potent treatment protocols. This process has paid off well. Programmatic treatment development is needed for many disorders to address myriad questions. What are the essential disorder-specific family processes that should be targeted by interventions? Hostility, criticism, communication, attachment and autonomy, attributional sets, and behavior management are important processes of family life, but each may have more relative importance for specific disorders. With a greater understanding of these processes, treatments could be tailored to target these mechanisms more efficiently and effectively. (ABSTRACT TRUNCATED)
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PMID:Current status of family intervention science. 1144 17


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