Risperidone and adaptive behavior in children with autism

OBJECTIVE: To evaluate the impact of risperidone on adaptive behavior in children with autistic disorder who have serious behavior problems and to examine different methods of scoring the Vineland Adaptive Behavior Scales to measure change. METHOD: Forty-eight children (5 years to 16 years, 5 months) who showed behavioral improvement during acute treatment with risperidone were followed for 6 months and assessed with the Vineland Scales. RESULTS: Raw scores, age-equivalents, and special norm percentile scores all showed significant increases in adaptive behavior in the areas of communication, daily living skills, and socialization (p <.01). During a period of 6 to 8 months, children gained an average of 7.8 age-equivalent months in the area of socialization, a > 6% improvement beyond what would be expected based on baseline growth rates. CONCLUSIONS: Although limited by the absence of a control group, these results suggest that risperidone may improve adaptive skills in children with autistic disorder accompanied by serious behavioral problems. Vineland age-equivalent scores appear to be most useful in assessing change with treatment over time.     

A prospective open trial of guanfacine in children with pervasive developmental disorders

OBJECTIVE: A common complaint for children with pervasive developmental disorder (PDD) is hyperactivity. The purpose of this pilot study was to gather preliminary information on the efficacy of guanfacine in children with PDD and hyperactivity. METHODS: Children with PDD accompanied by hyperactivity entered the open-label trial if there was a recent history of failed treatment with methylphenidate or the child did not improve on methylphenidate in a multisite, placebo-controlled trial. RESULTS: Children (23 boys and 2 girls) with a mean age of 9.03 (+/-3.14) years entered the open-label trial. After 8 weeks of treatment, the parent-rated Hyperactivity subscale of the Aberrant Behavior Checklist (ABC) went from a mean of 31.3 (+/-8.89) at baseline to 18.9 (+/-10.37) (effect size = 1.4; p < 0.001). The teacher-rated Hyperactivity subscale decreased from a mean of 29.9 (+/-9.12) at baseline to 22.3 (+/-9.44) (effect size = 0.83; p < 0.01). Twelve children (48%) were rated as Much Improved or Very Much Improved on the Clinical Global Impressions- Improvement. Doses ranged from 1.0 to 3.0 mg/day in two or three divided doses. Common adverse effects included irritability, sedation, sleep disturbance (insomnia or midsleep awakening), and constipation. Irritability led to discontinuation in 3 subjects. There were no significant changes in pulse, blood pressure, or electrocardiogram. CONCLUSIONS: Guanfacine may be useful for the treatment of hyperactivity in children with PDD. Placebo-controlled studies are needed to guide clinical practice.     

Risperidone in the management of disruptive behavior disorders

Disruptive behavior disorders (DBDs) represent a spectrum of disorders, including conduct disorder and oppositional-defiant disorder. The atypical antipsychotic risperidone may be useful for the management of patients with DBDs. Clinical data on risperidone have demonstrated efficacy and satisfactory tolerability in improving angry, aggressive, self-injurious, and disruptive symptoms and behavior in children with pervasive developmental disorders and mood disorders. This paper reviews the results of recent studies that have evaluated the efficacy and safety of risperidone in the treatment of pediatric patients with DBDs. Because concerns have been raised regarding the safety of atypical antipsychotic treatment in pediatric patients, this paper further evaluates safety risks by presenting newly completed analyses of movement disorders, prolactin concentrations, body weight, and cognitive function data from short- and long-term studies in this patient population. A comprehensive review of all of the findings suggests that risperidone is an effective and well-tolerated treatment option for children and adolescents with DBDs. As with all antipsychotics, practitioners should monitor young patients' growth, weight, sexual maturation, and metabolic parameters.     

Pulmonary involvement in inflammatory bowel disease

Clinically significant pulmonary involvement in inflammatory bowel disease is uncommon, and presentation to thoracic surgeons is rare. A literature review found no such cases in the cardiothoracic surgery network (CTSNET) journals. We describe a patient presenting with a lung mass presumed to be lung cancer that ultimately transpired to be pulmonary involvement of inflammatory bowel disease.     

Novel clinical trial designs for treatment of ductal carcinoma in situ of the breast with trastuzumab (herceptin)

Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored.     

The endovascular management of intracranial vascular disease including the MERCI device

Opinion statement The prompt and aggressive management of acute stroke has become the standard of care as public awareness and the available successful treatment options both increase. The intravenous administration of tissue plasminogen activator within an established treatment window has been determined through large well-designed studies. The endovascular strategies for acute stroke have evolved significantly over the past 5 years and have been prompted by the limits of the intravenous treatment, as well as by the desire to demonstrate improved recanalization rates and improved long-term outcomes. Among these interventional treatment options are the intra-arterial administration of tissue plasminogen activator and newer antiplatelet agents, mechanical thrombectomy with the MERCI device, and intracranial angioplasty and stenting. This article outlines the major studies that have defined the current field of acute stroke management and discusses the basic treatment paradigms that are commonly used today.     

Arzoxifene: the evidence for its development in the management of breast cancer

Introduction:

Endocrine therapy is an important and integral part of breast cancer management. Selective estrogen receptor modulators (SERMs), such as tamoxifen, remain a vital component in the endocrine therapy armamentarium. However the “ideal SERM”, which has antagonist effects on the breast and endometrium but beneficial agonistic effects on bone and lipid profile, remains to be found.

Aim:

The aim of this review is to examine the evidence for arzoxifene as the “ideal SERM.”

Evidence review:

Arzoxifene showed initial promise as the “ideal SERM” in preclinical, phase I, and phase II clinical studies. It appeared to have powerful antiestrogenic effects on breast cancer and endometrium, with equally strong favorable estrogenic effects on bone and lipid profile, minimal side effects, and good oral bioavailability.However, phase III trial data found it to be inferior to tamoxifen, bringing an apparent end to its investigation as a breast cancer treatment.

Clinical potential:

Despite early promise as the “ideal SERM”, results from a phase III trial have relegated arzoxifene to research in breast cancer prevention and osteoporosis treatment.     

Parent satisfaction in a multi-site acute trial of risperidone in children with autism: a social validity study

Rationale Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer’s perspective will help to forge a better alliance between participants and researchers. Objective Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior. Method Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures. Results Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child’s research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would “definitely” recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of “learning tests”. Conclusions Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged. From the Research Units on Pediatric Psychopharmacology Autism Network.