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Biomedical subjects

Kimberly A Stigler

Publications and source records attributed to Kimberly A Stigler.

12 recordsLinked to original sources

A retrospective study of memantine in children and adolescents with pervasive developmental disorders.

RATIONALE: There are no drugs that have been shown to effectively treat the core social impairment of autism. OBJECTIVES: The purpose of this study was to examine the effectiveness and tolerability of memantine for social impairment in children and adolescents with pervasive developmental disorders (PDDs). MATERIALS AND METHODS: Medical records of 18 patients with PDDs consecutively treated with open-label memantine were retrospectively reviewed. The data reviewed included prospectively obtained assessments of severity (S) and improvement (I) using the Clinical Global Impressions Scale (CGI). Pretrial and follow-up parent ratings were also available on six patients using the Aberrant Behavior Checklist (ABC). RESULTS: Eighteen patients (15 male, 3 female; mean age=11.4 years, range 6-19 years) received memantine (mean dosage=10.1 mg/day, range 2.5-20 mg/day) over a mean duration of 19.3 weeks (range 1.5-56 weeks). Eleven of 18 (61%) patients were judged responders to memantine based on a rating of "much improved" or "very much improved" on the CGI-I. Significant improvement was also seen on the CGI-S. Improvement was primarily seen clinically in social withdrawal and inattention. Adverse effects occurred in 7 of 18 (39%) patients and led to drug discontinuation in 4 of 18 (22%) patients. Thirteen of 18 (72%) patients received stable doses of concomitant medications during the memantine trial. CONCLUSIONS: In this open-label retrospective study, memantine was effective in a number of patients with PDDs. Controlled studies are warranted to further assess the efficacy and safety of memantine in PDDs.

Adolescent↗

Open-label atomoxetine for attention-deficit/ hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders.

OBJECTIVE: The aim of this study was to conduct an initial evaluation of the efficacy of atomoxetine for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with pervasive developmental disorders (PDDs). METHOD: Children with PDDs and a nonverbal IQ of >or=70 received atomoxetine (target dose 1.2-1.4 mg/kg/day) during the course of an 8-week, open-label, prospective study. Standardized assessments of efficacy and tolerability were collected at regular intervals during the trial. RESULTS: Sixteen children and adolescents (mean age 7.7 +/- 2.2 years, age range 6-14 years) with autistic disorder (n = 7), Asperger's disorder (n = 7), or PDD not otherwise specified (n = 2) received atomoxetine (mean dose 1.2 +/- 0.3 mg/kg/day). Twelve participants (75%) were rated as "much" or "very much improved" on the Clinical Global Impressions-Improvement scale. The most significant improvement was seen in the area of ADHD symptoms as measured by the SNAP-IV and Aberrant Behavior Checklist (effect size = 1.0-1.9). Improvements of lesser magnitude (effect size = 0.4-1.1) were seen in irritability, social withdrawal, stereotypy, and repetitive speech. There were no significant changes on the Conners' Continuous Performance Test. Atomoxetine was well tolerated with the exception of 2 participants (13 %) who stopped medication due to irritability. Weight decreased by a mean of 0.8 kg during the 8-week trial. CONCLUSIONS: Placebo-controlled studies are indicated to determine atomoxetine's efficacy for ADHD symptoms in PDDs.

Adolescent↗

Ramelteon for insomnia in two youths with autistic disorder.

OBJECTIVE: The aim of this study was to report preliminary data on the effectiveness and tolerability of ramelteon for the treatment of insomnia in youth with autistic disorder (autism). METHOD: Two youths, ages 7 and 18 years, with autism and significant insomnia characterized by problems with sleep onset and maintenance received an open-label trial of ramelteon (4-8 mg) over a duration of 16-18 weeks. RESULTS: Target symptoms of delayed sleep onset and/or frequent nocturnal awakening improved significantly, as determined by Clinical Global Impressions-Improvement (CGI-I) scale ratings of either "much improved" or "very much improved." Ramelteon was well tolerated. No daytime sedation was reported. CONCLUSIONS: This case report illustrates the potential effectiveness and tolerability of ramelteon for sleep disturbances in 2 patients with autism. Further research is needed to verify its safety, tolerability, and efficacy in children and adolescents with autism.

Adolescent↗

Gastrointestinal factors in autistic disorder: a critical review.

Interest in the gastrointestinal (GI) factors of autistic disorder (autism) has developed from descriptions of symptoms such as constipation and diarrhea in autistic children and advanced towards more detailed studies of GI histopathology and treatment modalities. This review attempts to critically and comprehensively analyze the literature as it applies to all aspects of GI factors in autism, including discussion of symptoms, pathology, nutrition, and treatment. While much literature is available on this topic, a dearth of rigorous study was found to validate GI factors specific to children with autism.

Autistic Disorder↗

Risperidone in pervasive developmental disorders.

Atypical antipsychotics are increasingly used in the treatment of severe behavioral disturbances in people with pervasive developmental disorders. Among these compounds, risperidone has been the most broadly studied. This drug profile will review the available data on the use of risperidone in individuals with pervasive developmental disorders. In addition, the chemistry, pharmacokinetics, pharmacodynamics and metabolism of risperidone are discussed. Emphasis will be placed on adverse effects associated with risperidone in these people, including a discussion of measures that can be taken to monitor for these effects. Finally, a discussion of the future direction of risperidone use in this population and key issues will be presented.

Antipsychotic Agents↗

Neurochemistry in the pathophysiology of autism.

Significant progress has been made in the search for underlying pathophysiologic mechanisms in autism over the past 50 years. The cause of the disorder, however, remains largely unknown. This article reviews neurochemical contributions to the pathophysiology of autism with a focus on monoamines, glutamate/gamma-aminobutyric acid systems, and neuropeptides. As these efforts move forward, it will be important to begin to integrate genetic studies with those involving neuroimaging and postmortem research in each of these 3 areas, as well as with pharmacologic treatment approaches.

Adolescent↗

A naturalistic retrospective analysis of psychostimulants in pervasive developmental disorders.

OBJECTIVE: We set out to examine the effectiveness and tolerability of psychostimulants in children and adolescents with pervasive developmental disorders (PDDs). METHODS: Medical records of all patients with PDDs treated with a stimulant were retrospectively reviewed. Demographics, stimulant type, drug dosage, trial duration, and adverse effects were recorded. Global improvement, focused on symptoms of hyperactivity and inattention, was measured by the Clinical Global Impressions-Improvement scale, with positive response defined by a rating of much improved or very much improved. RESULTS: Of 195 patients (174 males, 21 females; mean age +/- SD = 7.26 +/- 3.45 years, range 2-19 years), 61 had more than one trial, resulting in a total of 274 separate stimulant trials. It was discovered that 24.6%, 23.2%, and 11.1% of patients with a history of one, two, or three stimulant trials, respectively, responded to their first stimulant trial. Among first trial nonresponders, 6 (14.0%) of 43 patients responded to a second trial. Of those who did not respond to their first or second stimulant trial, 2 (14.3%) of 14 patients responded to a third trial. Patients with Asperger's disorder, in contrast to those with autistic disorder or PDD not otherwise specified, were significantly more likely to respond to a stimulant trial (p < 0.01). Use of concomitant medication (p < 0.007) positively affected response, whereas no association was found between stimulant type and IQ and response. Adverse effects, including agitation, dysphoria, and irritability, often occurred (154 [57.5%] of 268 trials, with 6 missing values). CONCLUSIONS: Overall, stimulants appeared ineffective and poorly tolerated for the majority of patients with PDDs. Response may differ with PDD subtype. Controlled studies are needed to further evaluate these preliminary findings in a systematic manner.

Adolescent↗

Aripiprazole for maladaptive behavior in pervasive developmental disorders.

OBJECTIVE: The aim of this study was to obtain preliminary data regarding the effectiveness and tolerability of aripiprazole in the treatment of children and adolescents with a pervasive developmental disorder (PDD). METHOD: Five youths (mean age, 12.2 years; range, 5-18 years) meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for a PDD received a naturalistic, open-label trial of aripiprazole (mean dosage, 12.0 mg/day; range, 10-15 mg/day) for a minimum of 8 weeks (mean duration, 12 weeks; range, 8-16 weeks). RESULTS: All 5 patients were judged to be responders, as determined by a Clinical Global Impressions-Improvement (CGI-I) scale rating of "much improved" or "very much improved." Aripiprazole was well tolerated. No extrapyramidal symptoms or clinically significant changes in heart rate or blood pressure occurred during the short-term trials. Two of 5 patients experienced mild somnolence. Two subjects lost weight, 2 subjects had no change, and 1 subject gained weight (mean change, -8.2 lbs; range, -30 to +1 lb). The weight loss was likely the result of the discontinuation of atypical antipsychotics that had led to significant weight gain. CONCLUSIONS: This case series describes the effectiveness of aripiprazole in the treatment of maladaptive behaviors in 5 patients with a PDD. No significant adverse effects emerged during these short-term trials. Additional research is needed to support these preliminary findings.

Adolescent↗

Weight gain associated with atypical antipsychotic use in children and adolescents: prevalence, clinical relevance, and management.

Atypical antipsychotics are increasingly prescribed to children and adolescents with neuropsychiatric disorders. Although their profile of potent antagonism at specific serotonin and dopamine receptors offers certain advantages compared with typical antipsychotics, their use has been associated with various adverse effects, including significant weight gain. This adverse effect is of particular concern in children and adolescents, secondary to the immediate and long-term health risks associated with weight gain, including obesity, diabetes mellitus, and hyperlipidemia. Indeed, from 1963 to 1991, the prevalence of obesity has approximately doubled in youth. Prior to selecting an atypical antipsychotic, a detailed review of the predictors of weight gain is necessary for every child and adolescent. Published data suggest that clozapine and olanzapine are associated with considerable weight gain, whereas risperidone and quetiapine have a moderate risk. Alternatively, ziprasidone and aripiprazole may exhibit a low risk for this adverse effect. Whereas behavioral and pharmacologic measures are available to manage weight gain associated with atypical antipsychotics, research is needed to establish more effective and safe interventions for this adverse effect in children and adolescents.

Adolescent↗

A retrospective analysis of quetiapine in the treatment of pervasive developmental disorders.

BACKGROUND: The purpose of this study was to examine the effectiveness and tolerability of quetiapine for aggression, hyperactivity, and self-injury in pervasive developmental disorders (PDDs). METHOD: The medical records of all patients with PDDs diagnosed according to DSM-IV criteria and treated with quetiapine were retrospectively reviewed. Patients who received quetiapine for at least 4 weeks and who were not concurrently treated with another antipsychotic or mood stabilizer were included. Improvement was measured with the Clinical Global Impressions-Improvement scale (CGI-I), with response determined by ratings of "much improved" or "very much improved." Data were collected from May 15, 2003 through November 30, 2003. RESULTS: Of 857 records reviewed, 20 patients (16 male, 4 female) (mean +/- SD age = 12.1 +/- 6.7 years; range, 5-28 years) received a quetiapine trial (mean +/- SD dosage = 248.7 +/- 198.4 mg/day; range, 25-600 mg/day) over a mean duration of 59.8 +/- 55.1 weeks (range, 4-180 weeks). Eight (40%) of 20 patients were judged "responders" to quetiapine; the mean CGI-I score for the entire group was 3.0 +/- 1.1 (minimally improved). A statistically significant improvement (p = .002) was found between a mean pretrial CGI-Severity of Illness scale (CGI-S) score of 5.1 +/- 0.6 (markedly ill) and a posttrial CGI-S score of 4.2 +/- 1.1 (moderately ill). Adverse effects occurred in 50% (N = 10) of patients and led to drug discontinuation in 15% (N = 3) of patients. CONCLUSION: Quetiapine was modestly effective for maladaptive behavior in patients with a PDD. Controlled studies are needed to further assess these preliminary findings.

Adolescent↗

Treatment of aggression in children and adolescents with autism and conduct disorder.

The optimal clinical management of aggression in children and adolescents involves both behavioral and pharmacologic intervention strategies. This article reviews medication treatments for youngsters with autistic disorder and conduct disorder, conditions for which the pharmacologic management of aggression is often necessary. Efficacy results and associated adverse effects from selected clinical trials of most classes of psychotropic medications are discussed. While preliminary progress has been made in the development of medication treatments for these serious disorders of youth, additional controlled research and longitudinal studies are needed to better understand the efficacy and tolerability of currently available compounds within each diagnostic group.

Adolescent↗

The use of selective serotonin reuptake inhibitors in autism and related disorders.

This paper reviews the published literature on the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of symptoms associated with autistic disorder and other pervasive developmental disorders (PDDs) in both children and adults. To date, placebocontrolled studies of SSRIs have involved only fluvoxamine (in children and adults) and fluoxetine (in children). Open-label and retrospective studies of all other SSRIs in PDDs have also been published that suggest effectiveness. Despite these positive reports, there continues to be questions about the tolerability and appropriate dosing of SSRIs in children with PDDs. Because of the limited number of placebo-controlled studies, definitive conclusions about the role SSRIs should play in the clinical treatment of children with PDDs cannot be drawn. Larger, placebo-controlled studies of SSRIs are needed to guide clinical treatment.

Adult↗