Biomedical subjects

Robert L Findling

Publications and source records attributed to Robert L Findling.

At least 19 recordsLinked to original sources

PubMed2007

Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder.

This practice parameter reviews the literature on the assessment and treatment of children and adolescents with bipolar disorder. The parameter focuses primarily on bipolar 1 disorder because that is the type most often studied in juveniles. The presentation of bipolar disorder in youth, especially children, is often considered atypical compared with that of the classic adult disorder, which is characterized by distinct phases of mania and depression. Children who receive a diagnosis of bipolar disorder in community settings typically present with rapid fluctuations in mood and behavior, often associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders. Thus, at this time it is not clear whether the atypical forms of juvenile mania and the classic adult form of the disorder represent the same illness. The question of diagnostic continuity has important treatment and prognostic implications. Although more controlled trials are needed, mood stabilizers and atypical antipsychotic agents are generally considered the first line of treatment. Although patients may respond to monotherapy, combination pharmacotherapy is necessary for some youth. Behavioral and psychosocial therapies are also generally indicated for juvenile mania to address disruptive behavior problems and the impact of the illness on family and community functioning.

Adolescent↗

PubMed2007

Zonisamide for bipolar depression.

In recent years, research into bipolar depression has increased. Each year, more studies are published using different agents to treat this condition. In addition to effectiveness and tolerability, bipolar depression research has sought agents that do not induce cycling or mania. This paper evaluates an open-label pilot study on zonisamide for bipolar depression that examined the effectiveness and tolerability of this agent while observing for any switch to mania. Zonisamide was found to have a very low switch rate and modest effectiveness. However, a high dropout rate was observed--mostly due to side effects. Until further research is available, zonisamide is not recommended as a first-line treatment for bipolar depression.

Bipolar Disorder↗

PubMed2006

Psychopharmacology of pediatric bipolar disorder: a review.

RATIONALE: Pediatric bipolar disorder (PBD) is a chronic and debilitating psychiatric illness. It is associated with many short-term and long-term complications including poor academic and social performance, legal problems and increased risk of suicide. Moreover, it is often complicated by other serious psychiatric disorders including attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder and substance use disorders. For these reasons, there is a need for effective treatment for PBD. OBJECTIVES: To review available data from published reports of the treatment of PBD, highlighting those treatment practices for which there is scientific evidence. To suggest directions for future research. MATERIALS AND METHODS: A comprehensive Medline search was performed to identify published reports from 1995 to 2006. Reports with the greatest methodological stringency received greater focus. RESULTS: There is limited evidence from double-blind, placebo-controlled trials regarding the treatment of PBD. Available data suggests that lithium, some anticonvulsants and second-generation antipsychotics may be equally beneficial in the acute monotherapy for youth with mixed or manic states. However, because of limited response to acute monotherapy, there is increased justification for combination therapy. There is very limited data on the treatment of the depressed phase of bipolar illness in the youth. Also, very few studies have addressed the treatment of comorbidities and maintenance/relapse prevention in PBD. CONCLUSION: Although significant progress was made in the treatment of youth with bipolar disorder, there is a need for more methodologically stringent research to more precisely define evidence-based treatment strategies for PBD.

Adolescent↗

PubMed2006

Comparing the effects of sampling designs on the diagnostic accuracy of eight promising screening algorithms for pediatric bipolar disorder.

BACKGROUND: Past studies have used markedly different inclusion and exclusion criteria to form samples used to evaluate diagnostic tests, making it difficult to compare results across studies. The present investigation compared eight screening algorithms in the same sample but under two different design strategies. METHODS: The DSM-IV diagnoses were based on a semi-structured diagnostic interview (KSADS) with the parent and youth sequentially. Raters were blind to index test scores. Participants were 216 youths with bipolar spectrum diagnoses and 284 youths with other Axis I diagnoses or no diagnosis. T-tests evaluated whether areas under the curve (AUC) from receiver operating characteristic analyses differed under the two design conditions. RESULTS: All of the instruments discriminated bipolar cases better when inclusion and exclusion criteria duplicated those used in phenomenological research studies selecting narrow phenotypic cases (AUCs ranging from .90 to .81). The measures performed less well when more heterogeneous clinical presentations were included [AUCs ranging from .86 to .69, t(8) = 4.99, p = 001]. CONCLUSIONS: Results indicate that checklists perform less well discriminating pediatric bipolar disorder under conditions that more closely resemble clinical practice. Test users must consider whether the sampling strategies and participant characteristics used to evaluate tests match the characteristics of their own patients.

Adolescent↗

PubMed2006

Classification of adolescent psychotic disorders using linear discriminant analysis.

BACKGROUND: The differential diagnosis between schizophrenia and bipolar disorder during adolescence presents a major clinical problem. Can these two diagnoses be differentiated objectively early in the courses of illness? METHODS: We used linear discrimination analysis (LDA) to classify 28 adolescent subjects into one of three diagnostic categories (healthy, N=8; schizophrenia, N=10; bipolar, N=10) using subsets from a pool of 45 variables as potential predictors (22 neuropsychological test scores and 23 quantitative structural brain measurements). The predictor variables were adjusted for age, gender, race, and psychotropic medication. All possible subsets composed of k=2-12 variables, from the set of 45 variables available, were evaluated using the robust leaving-one-subject-out method. RESULTS: The highest correct classification (96%) of the 3 diagnostic categories was yielded by 9 sets of k=12 predictors, comprising both neuropsychological and brain structural measures. Although each one of these sets misclassified one case, each set correctly classified (100%) at least one group, such that a fully correct diagnosis could be reached by a tree-type decision procedure. CONCLUSIONS: We conclude that LDA with 12 predictor variables can provide correct and robust classification of subjects into the three diagnostic categories above. This robust classification relies upon both neuropsychological and brain structural information. Our results demonstrate that, despite overlapping clinical symptoms, schizophrenia and bipolar disorder can be differentiated early in the course of disease. This finding has two important implications. Firstly, schizophrenia and bipolar disorder are different illnesses. If schizophrenia and bipolar are dissimilar clinical manifestations of the same disease, we would not be able to use non-clinical information to classify ('diagnose') schizophrenia and bipolar disorder. Secondly, if this study's findings are replicated, brain structure (MRI) and brain function (neuropsychological) used together may be useful in the diagnosis of new patients.

Adolescent↗

PubMed2006

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder.

OBJECTIVE: To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). METHODS: Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. RESULTS: The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. CONCLUSIONS: EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Prefrontal hemodynamic activity predicts false memory--a near-infrared spectroscopy study.

Evidence from lesion studies suggests an important role of the prefrontal cortex (PFC) in the reconstructive processes of episodic memory or memory distortion. Results from functional imaging studies imply PFC involvement during the illusionary recollection of non-experienced events. Here, we used a two-channel near-infrared spectroscopy (NIRS) system and conducted real-time monitoring of PFC hemodynamics, while subjects studied word lists and subsequently recognized unstudied items (false recognition). Bilateral increases in the oxygenated hemoglobin concentration ([oxy-Hb]) were observed during false recognition compared to true recognition, and a left PFC dominant increase of [oxy-Hb] was observed during encoding phases where subjects later claimed that they recognized unstudied words. Traces of semantic processing, reflected primarily in the left PFC activity, could eventually predict whether subjects falsely recognize non-experienced events.

Adult↗

PubMed2006

Diagnostic and measurement issues in the assessment of pediatric bipolar disorder: implications for understanding mood disorder across the life cycle.

The goal of this paper is to review assessment research of bipolar disorder in children and adolescents. The review addresses numerous themes: the benefits and costs of involving clinical judgment in the diagnostic process, particularly with regard to diagnosis and mood severity ratings; the validity of parent, teacher, and youth self-report of manic symptoms; how much cross-situational consistency is typically shown in mood and behavior; the extent to which a parent's mental health status influences their report of child behavior; how different measures compare in terms of detecting bipolar disorder, the challenges in comparing the performance of measures across research groups, and the leading candidates for research or clinical use; evidence-based strategies for interpreting measures as diagnostic aids; how test performance changes when a test is used in a new setting and what implications this has for research samples as well as clinical practice; the role of family history of mood disorder within an assessment framework; and the implications of assessment research for the understanding of phenomenology of bipolar disorder from a developmental framework.

Adolescent↗

PubMed2006

Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder.

The current study examined the pharmacokinetics (PK), safety, and tolerability of paroxetine after repeated multiple oral dosing in children and adolescents with major depressive or obsessive-compulsive disorder. In this 6-week, open-label, repeat dose, dose-rising study, 62 patients (27 children and 35 adolescents) were treated with paroxetine 10 mg/day for the first 2 weeks of the study, 20 mg/day for the next 2 weeks, and 30 mg/day for the final 2 weeks. Pharmacokinetic sampling and safety assessments occurred at baseline and subsequently on the final treatment day of each dosing level. Between-patient variability in PK was pronounced at the 10 mg dose level, but markedly reduced at higher doses. A supra-proportional increase in plasma concentrations with increasing dose was evident in both age groups. Data for C(max) and AUC(0-24) indicated that, at each dose level, paroxetine steady-state systemic exposure was higher in children than in adolescents. The differences between age groups, however, diminished with each increasing dose, and were virtually abolished when differences in weight among different age groups were considered. Stepwise regression analysis indicated that both oral clearance and volume of distribution were highly dependent on paroxetine dose, cytochrome P4502D6 genotype, and weight (p<0.0001), but not age or sex. Paroxetine was generally safe and well tolerated in both age groups, with the most frequently observed adverse events being largely consistent with those observed in prior paroxetine studies of adult psychiatric patients. Certain gastrointestinal and behavioral activation events (aggressive reaction and nervousness) were reported more frequently in the youngest age group.

Adolescent↗

PubMed2006

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.

Adolescent↗

PubMed2006

Combination lithium and divalproex sodium in pediatric bipolar symptom re-stabilization.

OBJECTIVE: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of re-stabilization after the resumption of lithium (Li) plus divalproex (DVPX) following relapse on either agent as monotherapy. METHOD: This is a prospective, 8-week, open-label outpatient Li/DVPX combination therapy trial. Patients ages 5 to 17 years with bipolar disorder type I or II, who had achieved symptom remission with Li/DVPX combination therapy and subsequently relapsed during treatment with Li or DVPX monotherapy were enrolled between January 1999 and January 2003. RESULTS: Thirty-eight patients with a mean age of 10.5 years entered the study. Thirty-four (89.5%) patients responded to treatment with Li/DVPX mood stabilizer therapy alone, but four patients required adjunctive antipsychotic treatment to address residual symptomatology. Overall, reinitiation of Li/DVPX combination therapy was well tolerated with no subjects discontinuing because of a medication-related adverse event. CONCLUSIONS: It appears that most youths with bipolar disorder who stabilize on combination Li/DVPX therapy and subsequently relapse during monotherapy can safely and effectively be re-stabilized with the reinitiation of Li/DVPX combination treatment.

Adolescent↗

PubMed2006

A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression.

OBJECTIVE: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. METHOD: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with escitalopram (10-20 mg/day; n = 131) or placebo (n = 133). Randomization was not stratified by age. The primary efficacy measure was the mean change from baseline to endpoint in Children's Depression Rating Scale-Revised (CDRS-R) scores, using the last observation carried forward approach. RESULTS: A total of 82% of patients completed treatment. Escitalopram did not significantly improve CDRS-R scores compared to placebo at endpoint (least squares mean difference = -1.7, p = .31; last observation carried forward). In a post hoc analysis of adolescent (ages 12-17 years) completers, escitalopram significantly improved CDRS-R scores compared with placebo (least squares mean difference = -4.6, p = .047). Headache and abdominal pain were the only adverse events in >10% of patients in the escitalopram group. Discontinuation rates caused by adverse events were 1.5% for both groups. Potential suicide-related events were observed in one escitalopram- and two placebo-treated patients. There were no completed suicides. CONCLUSIONS: Although there were no significant differences between escitalopram and placebo in the total population, the data suggest that escitalopram may have beneficial effects in adolescent patients. Escitalopram appeared to be well tolerated.

Adolescent↗

PubMed2006

Effectiveness, safety, and pharmacokinetics of quetiapine in aggressive children with conduct disorder.

OBJECTIVE: To provide an initial description of the effectiveness and pharmacokinetics (PK) of quetiapine in aggressive children with conduct disorder (CD). METHOD: This 8-week, open-label outpatient trial, enrolled patients ages 6 to 12 years with CD. Outcome measures included the Rating of Aggression Against People and/or Property Scale (RAAPPS), Nisonger Child Behavior Rating Form (NCBRF), and the Conners Parent Rating Scale (CPRS-48). Blood sampling for PK analyses occurred at the end of weeks 2 and 8. RESULTS: Seventeen children (16 boys, mean age 8.9 years) were treated. The mean dose at week 8 was 4.4 mg/kg (SD = 1.1 mg/kg). Significant decreases in the baseline scores of the RAAPPS, and several subscales of the NCBRF and the CPRS were found by the end of the study (p <.05). No patients discontinued because of an adverse event. No patients experienced extrapyramidal side effects. Quetiapine disposition was linear over the dose range studied. The elimination half-life of the drug averaged 3.9 and 2.9 hours and total body clearance averaged 3.5 and 3.0 L/hr/kg after study weeks 2 and 8, respectively. CONCLUSIONS: These preliminary data suggest that aggressive children with CD may benefit from quetiapine. The PK of quetiapine supports twice-daily dosing in children with CD.

Aggression↗

PubMed2006

Postpartum depression: a randomized trial of sertraline versus nortriptyline.

Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared. The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase. Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible. Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy. Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data. The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks. Times to response and remission also did not differ. Psychosocial functioning improved similarly in both drug-treated groups of mothers. The total side effect burden of each drug was similar, although side effect profiles differed between agents. No clinical or demographic variables differentiated responders by drug. Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP. Breast-fed infant serum levels were near or below the level of quantifiability for both agents.

Adaptation, Psychological↗

PubMed2006

Cognitive-behavioral therapy for bipolar disorders in adolescents: a pilot study.

OBJECTIVES: To develop a cognitive behavioral intervention for adolescents with bipolar disorders, test its feasibility and preliminary efficacy. METHODS: Based on existing research, a manualized, individually delivered cognitive behavioral intervention was developed and tested with adolescents with bipolar disorders as an adjunct to pharmacological treatment. Using existing data, baseline characteristics and outcome were compared to a matched group of eight adolescents with bipolar disorders who did not receive any psychosocial intervention. RESULTS: Preliminary results support the feasibility and efficacy of this manualized cognitive behavioral intervention. CONCLUSIONS: Individually delivered cognitive-behavioral therapy (CBT) as an adjunct to pharmacological treatment is feasible and associated with symptom improvement in adolescents with bipolar disorders. Randomized controlled studies are needed.

Adolescent↗

PubMed2006

A double-blind, randomized, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents.

OBJECTIVE: This multicenter trial examined the efficacy and safety of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. METHOD: A total of 116 outpatients 7 to 18 years of age with bipolar I disorder, manic or mixed, were recruited at 20 centers in the United States and randomly assigned to receive 7 weeks of double-blinded, flexibly dosed treatment with oxcarbazepine (maximum dose 900-2400 mg/day) or placebo. The primary efficacy measure was the mean change from baseline to endpoint in the Young Mania Rating Scale (YMRS), using the last-observation-carried-forward method. RESULTS: Oxcarbazepine (mean dose=1515 mg/day) did not significantly improve YMRS scores at endpoint compared with placebo [adjusted mean change: oxcarbazepine, -10.90 (N=55); placebo, -9.79 (N=55)]. Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of the patients in the oxcarbazepine group with an incidence at least twice that of the placebo group. The majority of adverse events were mild to moderate and occurred during the titration period. Eleven patients (19%) in the oxcarbazepine group discontinued the study because of adverse events, compared with two (4%) in the placebo group. CONCLUSIONS: Oxcarbazepine is not significantly superior to placebo in the treatment of bipolar disorder in youths. While the overall adverse event profile was similar to that reported for patients with epilepsy, the incidence of psychiatric adverse events for both the oxcarbazepine and placebo groups was higher than that reported for the epilepsy population.

Adolescent↗

PubMed2006

Validation of the Mood Disorder Questionnaire for bipolar disorders in adolescents.

OBJECTIVE: The study was designed to determine the validity of the Mood Disorder Questionnaire-Adolescent Version (MDQ-A) as a screening instrument for bipolar disorders (I, II, not otherwise specified, and cyclothymia) in an adolescent outpatient psychiatric population. METHOD: 104 adolescents and their parents completed the MDQ-A. Three versions of the MDQ-A were compared: (1) self report of symptoms by adolescent, (2) attributional report-how the adolescent believed teachers or friends would report his/her symptoms, and (3) parent report of adolescent's symptoms. DSM-IV diagnosis was made based upon the clinician-administered Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), a semistructured diagnostic interview. MDQ-A items were summed, yielding a score for each adolescent ranging from 0 to 13 on each of the 3 MDQ-A versions. Each possible scoring threshold, in combination with co-occurrence of symptoms and behaviors and with moderate to serious problems caused by symptoms, was crossed with the results of the K-SADS-PL diagnostic interview to assess sensitivity and specificity. The study was conducted from April 2002 to September 2003. RESULTS: A score of 5 or more items on the parent version yielded a sensitivity of 0.72 and specificity of 0.81, which were superior to self and attributional versions. CONCLUSIONS: The MDQ-A completed by parents about their adolescents' symptoms may be a useful screening instrument for bipolar disorders in an adolescent psychiatric outpatient population.

Adolescent↗

PubMed2006

Juvenile maladaptive aggression: a review of prevention, treatment, and service configuration and a proposed research agenda.

OBJECTIVE: To review prevention programs, psychosocial and psychopharmacologic treatments, and service delivery configurations for children and adolescents with maladaptive aggression. To propose a research agenda for disorders of aggression in child and adolescent psychiatry. DATA SOURCES: Recent empirical studies were reviewed using searches of MEDLINE and PsycINFO (text terms: aggression, antisocial, violence, conduct, oppositional, psychosocial treatment, psychopharmacology, and prevention), relevant books, review articles, and bibliographies. DATA EXTRACTION: Articles met the following criteria: published in an English-language, peer-reviewed journal between 1980 and 2005, included a focus on individuals < 18 years old, and included an outcome measure of relevant significance. STUDY SELECTION: Results of 154 randomized, controlled psychosocial treatment trials, 20 controlled psychopharmacology studies, 4 open-label medication studies, and 2 psychopharmacology meta-analyses were reviewed. RESULTS: Prevention programs show promise for reducing future aggression in at-risk populations. Empirical support is available for the effectiveness of multifocused psychosocial treatments in reducing aggression in children and adolescents. Atypical antipsychotics, lithium, divalproex sodium, and stimulants for conduct problems associated with attention-deficit/hyperactivity disorder have empirical support for reducing aggression in selected patient populations. CONCLUSIONS: Therapeutic nihilism in the treatment of aggressive children and adolescents with conduct problems is no longer warranted. Multifocused psychosocial interventions given early in life to at-risk children have the most support for effectiveness. However, treatments for children who routinely present to the child psychiatrist with already well-established disorders of aggression are neither robust nor well-established. Further research into maladaptive aggression in referred children and adolescents within and across psychiatric diagnoses is important for the field of child and adolescent psychiatry.

Adolescent↗