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Biomedical subjects

Robert L Findling

Publications and source records attributed to Robert L Findling.

At least 55 records · Page 3Linked to original sources

Effects of adolescent manic symptoms on agreement between youth, parent, and teacher ratings of behavior problems.

BACKGROUND: Little is known about the extent to which manic symptoms might influence the self-report ratings of adolescents as compared to parent and teacher ratings, although there are clinical reasons to believe that mania would increase disagreement. METHODS: Parents and youths between the ages of 11 and 17 years were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), Young Mania Rating Scale, and Child Depression Rating Scale-Revised. Based on the KSADS results, subjects were assigned to either a bipolar spectrum group (e.g., meeting criteria for a diagnosis of bipolar I, II, cyclothymia, or NOS) or a "nonbipolar" group (including depressive disorders, disruptive behaviors disorders, and other axis I diagnoses). Parents and youths both completed the Achenbach rating scales and the General Behavior Inventory (GBI). Teachers also completed the Achenbach scales. RESULTS: Youth self-report of manic symptoms showed lower correlations with clinician ratings than did parent ratings. Youths with a bipolar diagnosis also show poorer agreement about their depressive symptoms. There was some evidence that bipolar youths underreported symptoms, even after controlling for parent history of mood disorder. The youth's own manic symptoms partially mediated the effect of a bipolar diagnosis on rater disagreement. LIMITATIONS: Diagnoses and mood ratings were based on both parent and youth interviews. CONCLUSIONS: Findings strongly suggest that cross-informant agreement can be substantially affected by the youth's own psychopathology. Youths with a bipolar diagnosis tend to underreport their manic symptoms compared to parental report. Results emphasize the importance of gathering collateral sources of information in evaluating juvenile mania, and also suggest that parent reported problems should not be discounted out of hand.

Adolescent↗

Hemodynamic differences in the activation of the prefrontal cortex: attention vs. higher cognitive processing.

Both simple attention tasks (e.g. letter cancellation) and most tasks of higher cognitive processing (e.g. word generation) are known to activate the dorsolateral prefrontal cortex (PFC). While attention and higher cognitive processing differ phenomenologically, with attention tasks requiring great subjective effort despite their simplicity, possible physiological differences in the activation of the PFC between the two types of cognitive processing have remained uninvestigated. Hemodynamic changes in the PFC during activation due to tasks of attention and those of higher cognitive processing were examined using near-infrared spectroscopy in 10 Japanese and 10 American healthy adults. In tasks of higher cognitive processing, which included both verbal and non-verbal tasks, the concentration of oxygenated hemoglobin ([HbO2]) increased, and that of deoxygenated hemoglobin ([HbR]) decreased, with an increase in the tissue hemoglobin saturation (THS). In tasks of attention, which consisted of the letter cancellation and continuous performance test, both [HbO2] and [HbR] increased, with no significant changes in the THS observed. The distinctive patterns of hemodynamic changes were not affected by the factors of task difficulty or language. The change in [HbR] may be a physiological marker of the prefrontal lobe activation that discriminates between attention and higher cognitive processing. The increase in [HbR] suggests increased oxygen consumption of the PFC during tasks of attention, which might be related to the disproportionately great subjective effort associated with sustained attention. The physiological alteration in hemodynamic patterns according to changes in cognition needs to be examined in subjects with prefrontal lobe dysfunction, such as schizophrenia and mood disorder.

Adolescent↗

Somatic treatment for depressive illnesses in children and adolescents.

Numerous somatic interventions have been studied as potential treatments of depressive disorders in children and adolescents. These include antidepressant medications, light therapy, electro-convulsive therapy, and alternative therapies. The available evidence suggests that several somatic interventions hold promise as potentially safe and effective treatments for depressed youths; however, there is still much to be learned about these interventions. This article reviews what is known and what needs to be learned about the somatic treatment of pediatric depression.

Adolescent↗

International consensus statement on attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and treatment practice suggestions.

Researchers and clinicians worldwide share concerns that many youngsters with attention-deficit/hyperactivity disorder (ADHD) and/or disruptive behaviour disorders (DBDs) do not receive appropriate treatment despite availability of effective therapies. At the request of Johnson and Johnson (sponsor), 11 international experts in child and adolescent psychiatry were selected by Professor Stan Kutcher (chair) to address these concerns. This paper describes the experts' consensus conclusions, including treatment practice suggestions for physicians involved in the early treatment of youngsters with ADHD (or hyperkinetic disorder, in countries preferring this classification) and/or DBDs internationally: suggested first-line treatment for ADHD without comorbidity is psychostimulant medication aided by psychosocial intervention. For ADHD with comorbid conduct disorder (CD), psychosocial intervention combined with pharmacotherapy is suggested. For primary CD, suggested first-line treatment is psychosocial intervention, with pharmacotherapy considered as an 'add-on' when aggression/impulsivity is marked and persistent. Pharmacotherapy requires careful titration; full-day coverage is the suggested goal. Regular long-term follow-up is recommended.

Attention Deficit Disorder with Hyperactivity↗

Quetiapine in nine youths with autistic disorder.

OBJECTIVE: The aim of this study was to examine the effectiveness of quetiapine in adolescents suffering from autistic disorder (AD). METHODS: This was a 12-week, open-label study, for which medically healthy patients with AD between the ages of 10 and 17 years were eligible. Quetiapine treatment was gradually increased over the first 6 weeks of the study, to a total daily dose of 300 mg/day. Doses could then be increased to a maximum daily dose of 750 mg/day. Outcome measures included the Children's Psychiatric Rating Scale (CPRS) and the Clinical Global Impressions (CGI) scale. RESULTS: Nine (9) males were enrolled. Six (6) patients had previously been treated with other psychotropic agents. Although improvements in several symptom domains were observed on quetiapine, only 2 patients met a priori criteria for response ("much" or "very much improved" on the Clinical Global Impressions-Improvement Scale). In addition, only these same 2 patients' parents/guardians chose to continue quetiapine pharmacotherapy after study participation. CONCLUSIONS: These data suggest that quetiapine may not be a particularly effective agent in the treatment of adolescent patients with AD. However, should future studies be performed, it seems reasonable that they be conducted with more rigor, less treatment-resistant cohorts, and, possibly, a different dosing strategy.

Adolescent↗

Elevated thyrotropin in bipolar youths prescribed both lithium and divalproex sodium.

OBJECTIVE: To examine the effect of combined lithium and divalproex sodium on thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorders and to identify risk factors for lithium-induced hypothyroidism. METHOD: Bipolar youths aged 5 to 17 years participating in an open-label clinical trial received treatment with lithium and divalproex sodium for up to 20 weeks. TSH levels were measured at baseline and at the end of the study. Subjects were divided into two groups for analysis: group 1 had TSH levels of less than 10.0 mU/L at the end of the study and group 2 had TSH levels of 10.0 mU/L or more at end of the study. RESULTS: Twenty of the 82 subjects (24.4%) showed TSH elevations of at least 10 mU/L within an average exposure of less than 3 months. The mean baseline TSH level for group 2 was significantly higher than for group 1 (2.97 [SD = 1.48] versus 2.05 [SD = 0.89], p <.05). Mean lithium levels at the end of the study were 1.00 mEq/L for group 2 compared to 0.76 mEq/L for group 1 (t = -2.41, p =.019). CONCLUSIONS: Lithium is associated with significant rates of thyrotropin elevation in bipolar youths. Factors associated with elevation in TSH in lithium-treated subjects include a higher baseline TSH level and a higher lithium level. Close monitoring of thyroid function in children and adolescents taking lithium is recommended.

Adolescent↗

A prospective study of stimulant response in preschool children: insights from ROC analyses.

OBJECTIVE: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. METHOD: Twenty-eight preschoolers (ages 4.0 - 5.9) participated in the present investigation. They were obtained consecutively from a large sample of suburban children assessed for attention-deficit/hyperactivity disorder. After having received various dosing levels of a stimulant in a placebo-controlled crossover design, best dose was assigned based on the lowest Abbreviated Symptoms Questionnaire T score received in a given week. All analyses compared best dose ratings to placebo ratings. RESULTS: Preschoolers' behavioral ratings by parents and teachers were improved as a function of stimulant medication. More than 82% of the medicated sample improved their behavioral rating by at least 1 SD as demonstrated by receiver operating characteristic (ROC) analyses, with more than 50% of medicated preschoolers improving by more than 2 SD. Side effects were infrequent at best dose of medication. CONCLUSIONS: Clinically significant changes in behavioral ratings of preschoolers were noted in response to stimulant medication. Both stimulants were well tolerated. ROC curves were useful for clearly depicting on a case-by-case basis how much improvement was derived from psychopharmacological treatment.

Amphetamines↗

Comparing the diagnostic accuracy of six potential screening instruments for bipolar disorder in youths aged 5 to 17 years.

OBJECTIVE: To compare the diagnostic efficiency of six index tests as predictors of juvenile bipolar disorder in two large outpatient samples, aged 5 to 10 and 11 to 17 years, gathered from 1997 to 2002. METHOD: DSM-IV diagnosis was based on a semistructured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children) with the parent and youth sequentially, blind to scores on the index tests. Participants were 318 youths aged 5 to 10 (50% with bipolar diagnoses) and 324 youths aged 11 to 17 (41% with bipolar diagnoses). Areas under the curve (AUCs) from receiver operating characteristic analyses and multilevel likelihood ratios quantified test performance. RESULTS: Parent report (AUCs from 0.78 to 0.84 in both age groups) outperformed teacher (AUCs 0.57 in the younger sample and 0.70 in the older sample) or adolescent measures (AUCs 0.67 [General Behavior Inventory] and 0.71 [Youth Self-Report]) at identifying bipolar disorders. Combining tests did not produce clinically meaningful classification improvement. CONCLUSIONS: Parent report was more useful than teacher report or adolescent self-report on the index tests studied. Results generally replicated across both age groups. Parent report on these instruments could facilitate differential diagnosis of bipolar disorder in youths aged 5 to 17 years, especially by decreasing the rate of false-positive diagnoses.

Adolescent↗

Fluoxetine treatment for prevention of relapse of depression in children and adolescents: a double-blind, placebo-controlled study.

OBJECTIVE: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of < or =28 during treatment with fluoxetine 20 to 60 mg. METHOD: In this 32-week relapse-prevention phase of a double-blind, multicenter, placebo-controlled 51-week study, 20 patients continued to receive their fixed dose of fluoxetine (F/F group), while 20 similar patients were switched to placebo (F/P group). Definition of relapse for the primary analysis was a Children's Depression Rating Scale, Revised score of >40 with a 2-week history of clinical deterioration or relapse in the opinion of the physician. Adverse events were compared between treatment groups to assess discontinuation-emergent adverse events. RESULTS: Mean time to relapse was longer in the F/F recipients than in the F/P recipients (p=.046). Relapse occurred in an estimated 34% in the F/F cohort and 60% in the F/P cohort. Incidence of adverse events and tolerability were similar in the F/F and F/P groups, suggesting that fluoxetine is not associated with significant discontinuation events. CONCLUSIONS: Fluoxetine 20 to 60 mg/day was well tolerated and can significantly delay relapse of major depressive disorder symptoms in children and adolescents.

Administration, Oral↗

Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology.

OBJECTIVE: To improve the gathering of adverse events (AEs) in pediatric psychopharmacology by examining the value and acceptability of increasingly detailed elicitation methods. METHOD: Trained clinicians administered the Safety Monitoring Uniform Report Form (SMURF) to 59 parents and outpatients (mean age +/- SD = 11.9 +/- 3.2 years) in treatment, with 36% on stimulants, 29% on selective serotonin reuptake inhibitor drugs, 10% on both, and 25% on other drug combinations. The SMURF included a brief general inquiry, a drug-specific inquiry, and a comprehensive body system review (BSR). RESULTS: SMURF administration took 24.6 +/- 13.9 minutes (median, 21). The BSR took 15.5 +/- 8.1 minutes (median, 14) longer (p < .0001) than the general inquiry (4.3 +/- 5.4 minutes) and the drug-specific inquiry (4.2 +/- 2.9 minutes). The general inquiry elicited 48 AEs, the drug-specific inquiry elicited 16 additional AEs, and the BSR 129 additional AEs. Of all the clinically relevant AEs elicited by the SMURF (n = 36), 19 (53%) were elicited by the BSR. The BSR length and detail were acceptable to parents but not to clinicians. CONCLUSIONS: The BSR elicited additional clinically significant AEs that had been missed with less detailed methods. Parents, but not clinicians, rated satisfaction and acceptability of the BSR as good.

Adolescent↗

Long-term, open-label study of risperidone in children with severe disruptive behaviors and below-average IQ.

OBJECTIVE: This study determined the long-term safety and effectiveness of risperidone in treating severe disruptive behavior in children with subaverage intelligence. METHOD: This 48-week, open-label extension included 107 children ages 5-12 years with severe disruptive behavior disorders (according to DSM-IV criteria and a score of > or = 24 on the conduct problem subscale of the Nisonger Child Behavior Rating Form) and subaverage intelligence (IQ 36-84) who completed at least 2 weeks of a randomized, double-blind, placebo-controlled study of risperidone. All patients received 0.02-0.06 mg/kg/day of oral risperidone; the purpose was to accumulate long-term safety data. Scores on the Nisonger Child Behavior Rating Form were also obtained. RESULTS: The mean risperidone dose was 1.5 mg/day. The most common adverse events reported were somnolence (33%), headache (33%), rhinitis (28%), and weight gain (21%). Somnolence was usually mild and transient. The mean weight increase was 5.5 kg; half was attributable to developmentally expected growth. Transient and asymptomatic increases in prolactin levels were observed. There were no significant changes in Extrapyramidal Symptom Rating Scale scores and no cases of tardive dyskinesia. No clinically relevant changes in ECGs or vital signs were noted. Risperidone was associated with rapid, significant improvement on the conduct problem subscale score of the Nisonger Child Behavior Rating Form in patients previously treated with placebo; improvement was maintained during long-term treatment and in patients previously given risperidone. CONCLUSIONS: Long-term risperidone appears to be generally safe, well tolerated, and effective for treating severely disruptive behaviors in children with subaverage intelligence.

Antipsychotic Agents↗

A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.

OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28. RESULTS: The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group. CONCLUSIONS: In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated.

Adolescent↗

Prevention of postpartum depression: a pilot randomized clinical trial.

OBJECTIVE: The authors attempted to reduce the rate of postpartum depression in high-risk women and to increase the time to recurrence. METHOD: Nondepressed pregnant women with at least one past episode of postpartum major depression were recruited into a randomized clinical trial. Mothers were assigned randomly to a 17-week trial of sertraline or placebo immediately after birth and assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression. RESULTS: Of 14 subjects who took sertraline, one (7%) suffered a recurrence. Of eight subjects who were assigned to placebo, four (50%) suffered recurrences. This difference was significant. The time to recurrence was significantly longer in the sertraline-treated women than in the placebo-treated women. CONCLUSIONS: Sertraline conferred preventive efficacy for postpartum-onset major depression beyond that of placebo.

Adult↗

Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children.

Attention-deficit hyperactivity disorder (ADHD) is a common condition during childhood that is associated with significant psychosocial dysfunction. Psychostimulants are the compounds that have been most extensively studied for the treatment of ADHD in children. There is substantial scientific evidence that several methylphenidate- and amphetamine-based preparations have acute efficacy in the treatment of this condition in children. The short-term safety and tolerability of these compounds has been reasonably well-studied and the risks associated with psychostimulant therapy in the short-term are generally acceptable. However, the amount of long-term effectiveness and safety data relating to these compounds is relatively small. Data that do exist suggest that long-term treatment with psychostimulants in appropriately diagnosed patients may be associated with salutary effects as well as relatively modest risks. Until more extensive, methodologically rigorous data are available, it appears that judicious psychostimulant pharmacotherapy of ADHD in children may be justified.

Appetite↗

Pharmacologic treatment of adolescent and child schizophrenia.

Although relatively rare in childhood, the incidence of schizophrenia increases in adolescence. Compared with adult-onset schizophrenia, there are differences in the response to various psychopharmacologic agents and an urgent need for more clinical treatment trials in child-onset schizophrenia. The history, epidemiology and clinical presentation of early- and very early-onset schizophrenia is reviewed with a focus on the available pharmacologic treatment literature. Information on the older typical antipsychotics, newer atypical antipsychotics and most promising new potential agents, their benefits and pitfalls are summarized. Acute management as well as continuation and maintenance therapy recommendations are made.

Adolescent↗

Atypical antipsychotics in the treatment of children and adolescents: clinical applications.

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Adolescent↗