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Biomedical subjects

R L Findling

Publications and source records attributed to R L Findling.

At least 19 recordsLinked to original sources
PubMed2005

New data on the use of lithium, divalproate, and lamotrigine in rapid cycling bipolar disorder.

The rapid cycling variant of bipolar disorder is defined as the occurrence of four periods of either manic or depressive illness within 12 months. Patients suffering from this variant of bipolar disorder have an unmet need for effective treatment. This review examines two major studies in an attempt to update understanding of the current therapies available to treat rapid cycling patients. The first trial compares lamotrigine versus placebo in 182 patients studied for 6 months. The second is a recently completed, 20-month trial comparing divalproate and lithium in 60 patients. Both trials had a double-blind, randomized parallel-group design. The data from the latter study indicate that there are no large differences in efficacy between lithium and divalproate in the long-term treatment of rapid cycling bipolar disorder. In addition, lamotrigine has the potential to complement the spectrum of lithium and divalproate through its greater efficacy for depressive symptoms.

Antimanic Agents↗
PubMed2001

Short-term cardiovascular effects of methylphenidate and adderall.

OBJECTIVE: The primary purpose of this study was to examine the cardiovascular effects of Adderall (ADL) in a clinic-based group of youths with attention-deficit/hyperactivity disorder ranging in age from 4 to 17 years. METHOD: One hundred thirty-seven patients were treated with either methylphenidate (MPH) or ADL. Youths prescribed MPH were given medication twice daily, and youths treated with ADL received medication once daily. Patients were evaluated under five conditions: baseline, placebo, 5 mg/dose, 10 mg/dose, or 15 mg/dose. Resting pulse, diastolic blood pressure, and systolic blood pressure were examined after 1 week at each treatment condition. Changes from baseline on these parameters were examined. RESULTS: The short-term cardiovascular effects of both ADL and MPH were modest. No patients experienced any clinically significant change in these cardiovascular measures during the course of this brief trial. CONCLUSION: Since the short-term cardiovascular effects of ADL appear minimal, specific cardiovascular monitoring during short-term ADL treatment at doses of 15 mg/day or less does not appear to be indicated. In addition, under similar conditions, using similar methods, both medication treatments led to changes in blood pressure and pulse that were clinically insignificant.

Adolescent↗
PubMed2001

Developmental aspects of psychostimulant treatment in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVES: To examine the relationship between age and short-term clinical response to psychostimulant treatment in youths with attention-deficit/hyperactivity disorder (ADHD) and to examine whether weight-corrected doses of optimized psychostimulant therapy varied as a function of patient age. METHOD: One hundred seventy-seven patients were treated with either methylphenidate (MPH) or Adderall (ADL). Sixty-six youths received ADL and 111 patients were treated with MPH. All youths were evaluated at baseline and after receiving a week of treatment at each blinded, randomized dose level (placebo, 5, 10, or 15 mg). A "best dose" for each patient was assigned before the medication blind was broken. Behavioral ratings by both teachers and parents were examined for dose and medication effects. RESULTS: The medications had similar efficacy in children and teenagers. Older youths, however, benefited from a smaller weight-adjusted dose of medication than did the younger children. Similar efficacy was observed between the medications. CONCLUSIONS: These data suggest that psychostimulants are equally effective in treating children and adolescents with ADHD. Adolescents with ADHD may not necessarily require more medication than younger children to achieve a similar therapeutic response.

Adolescent↗
PubMed2001

Paediatric psychopharmacology: closing the gap between science and practice.

Children and adolescents do not always respond to treatment with psychotropic agents in a similar fashion to adults. Differences in safety and therapeutic response may occur across the life cycle. For example, despite the fact that tricyclic antidepressants are traditionally the 'gold standards' of pharmacotherapy for depressed adults, it does not seem that youths with depression benefit from treatment with these agents [1]. Similarly, it appears that earlier age at onset is associated with a reduced propensity to respond to neuroleptics for patients with schizophrenia [2]. In addition, young patients have been noted to be at higher risk for developing neuroleptic-induced extrapyramidal side effects when compared to adults [3]. Simply put, what is known about the safety and effectiveness of psychotropic compounds in adults cannot necessarily be presumed to be applicable to teenagers or children.

Adolescent↗
PubMed2001

Prevention of recurrent postpartum depression: a randomized clinical trial.

BACKGROUND: Women who have suffered one episode of postpartum-onset major depression (PPMD) comprise a high-risk group for subsequent episodes. We conducted a double-blind, randomized clinical trial to test the efficacy of nortriptyline in the prevention of recurrent PPMD. METHOD: Nondepressed women who had at least one past episode of PPMD (Research Diagnostic Criteria) were recruited during pregnancy. Subjects were randomly assigned to nortriptyline or placebo. Treatment began immediately postpartum. Each subject was assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression and Research Diagnostic Criteria for recurrence of major depression. RESULTS: No difference was found in the rate of recurrence in women treated with nortriptyline compared with those treated with placebo. Of 26 subjects who took nortriptyline preventively, 6 (0.23, 95% exact confidence interval [CI] = 0.09 to 0.44) suffered recurrences. Of 25 subjects who took placebo, 6 (0.24, 95% exact CI = 0.09 to 0.45) suffered recurrence (Fisher exact p = 1.00). CONCLUSION: Nortriptyline did not confer additional preventive efficacy beyond that of placebo. The rate of recurrence of PPMD (one fourth of women) was unacceptably high.

Adult↗
PubMed2001

Discriminative validity of parent report of hypomanic and depressive symptoms on the General Behavior Inventory.

It often is difficult clinically to differentiate bipolar disorder from other mental health conditions in young people. This study evaluated a parent report measure of depressive and hypomanic/biphasic symptoms. Parents of 196 youths, who were 5 to 17 years old and presented at an outpatient research center, completed an adapted General Behavior Inventory (GBI). Factor analyses suggested two dimensions, depression (alpha = .97) and biphasic/hypomania (alpha = .95). Logistic regressions using these scales discriminated mood disorder versus disruptive behavior disorder or no diagnosis, unipolar versus bipolar disorder, and bipolar versus disruptive behavior disorder based on structured interviews. Classification rates exceeded 80%, and receiver operating characteristic analyses showed good diagnostic efficiency for the scales, with areas under the curve greater than .80. Results indicate that clinicians can use the parent-completed GBI to derive clinically meaningful information about mood disorders in youths.

Adolescent↗
PubMed2001

Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder.

OBJECTIVES: The primary purpose of this study was to describe the clinical presentation of bipolar I disorder (BP-I) as it occurs in children and adolescents and to assess whether the manifestations of BP-I were similar in both age groups. METHOD: Ninety youths between the ages of 5 and 17 years meeting full diagnostic symptom criteria for BP-I were included in this study. The diagnosis of BP-I was established for these youths based on the results of a semi-structured diagnostic interview and a clinical assessment by a child and adolescent psychiatrist. The course of a subset of these youngsters' illnesses was assessed using the Life Charting Method (LCM). Data regarding the clinical presentation, longitudinal history, psychiatric co-morbidities and parental psychopathology were also obtained. RESULTS: The clinical presentation of BP-I was similar in children and adolescents. Youths meeting diagnostic criteria for BP-I developed an average of approximately 5.8 of the 7 symptoms of mania during periods of elevated or irritable mood. BP-I was found to be a cyclic disorder characterized by high rates of rapid cycling (50%) with almost no inter-episode recovery. Almost 75% of these subjects also met diagnostic symptom criteria for a disruptive behavior disorder. High rates of mood disorders were found in fathers. CONCLUSIONS: These data suggest that the presentation of juvenile BP-I is a cyclic and valid clinical condition with manifestations on a continuum with the later-onset forms of this illness.

Adolescent↗
PubMed2000

A double-blind pilot study of risperidone in the treatment of conduct disorder.

OBJECTIVE: To examine whether risperidone is superior to placebo in the treatment of youths with conduct disorder. METHOD: This was a 10-week, randomized, double-blind, placebo-controlled study with 2 parallel arms. Ten youths were randomly assigned to receive placebo and 10 youths were randomly assigned to receive risperidone. Patients were seen weekly throughout the trial. Medications could be increased at weekly intervals during the first 6 weeks of the study from an initial dose of 0.25 mg or 0.50 mg each morning, depending on patient weight. Patients weighing less than 50 kg had a maximum total daily dose of risperidone of 1.5 mg. Patients weighing 50 kg or greater had a maximum total daily dose of risperidone of 3.0 mg. The primary outcome measure was the Rating of Aggression Against People and/or Property Scale. RESULTS: Risperidone was superior to placebo in ameliorating aggression on most measures. Risperidone was reasonably well tolerated, with none of the risperidone-treated patients developing extrapyramidal side effects. CONCLUSIONS: These data provide preliminary evidence that risperidone may have efficacy in the treatment of youths with conduct disorder. Because of the small sample size and the brief length of this study, further research is necessary to confirm these findings.

Adolescent↗
PubMed2000

Nefazodone pharmacokinetics in depressed children and adolescents.

OBJECTIVE: To describe the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents. METHOD: Depressed youths aged 7 to 17 years were eligible to participate. Intensive sampling for pharmacokinetic analyses of NFZ and 3 of its active metabolites was performed after single and multiple dose administration. Treatment was continued for 6 more weeks and titrated to maximize clinical response. RESULTS: Twenty-eight patients were enrolled. Systemic exposure to NFZ and 3 metabolites was generally higher in children than adolescents. NFZ and metabolite disposition profiles showed high intra- and interpatient variability. Compared to published data in adults, the half-life of NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta-chlorphenylpiperazine pharmacokinetic parameters were different in 5 patients determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well tolerated, and administration was associated with significant reductions (p < .001) in depressive symptoms. CONCLUSIONS: The pharmacokinetics of NFZ in pediatric patients is highly variable. NFZ appears to be safe in this small, short-term study. Pediatric patients who are poor metabolizers of CYP2D6 do not appear to be at increased risk for NFZ-associated adverse events. Open-label treatment of NFZ is associated with reductions in depressive symptoms.

Adolescent↗
PubMed2000

Paediatric uses of atypical antipsychotics.

Antipsychotics are commonly prescribed to children and adolescents. With the relatively recent availability of the atypical antipsychotics, physicians have begun prescribing these agents to young people in the hope of finding safe, effective alternatives to the typical antipsychotics. This report reviews what is currently known about the use of the atypical antipsychotics in young people. Most of the currently available data are based on case reports and case series. The results of only a handful of prospective trials pertaining to the use of the atypical antipsychotics in youths have been reported. Based on the available information, it appears that clozapine has a role in juvenile treatment resistant schizophrenia. When considered as a group, the 'first-line' atypical antipsychotics risperidone, olanzapine and quetiapine appear to have promise as treatments for several neuropsychiatric disorders in young people. These conditions include psychotic, mood, disruptive, movement and pervasive developmental disorders. Unfortunately, as has historically been the case, the demand to address the clinical needs of young patients with neuropsychiatric disorders has outpaced empirically based information. This is particularly important because significant side effects can occur when children or adolescents are treated with atypical antipsychotics. Since there is a paucity of short-term and almost no long-term safety data pertaining to these agents in young people, careful consideration must be made prior to initiating atypical antipsychotic treatment for a child or teenager. Based upon what is known about these agents, a rational approach to the use of these drugs in juveniles is offered.

Antipsychotic Agents↗
PubMed1999

A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls.

The purpose of this study was to compare thalamic size in adolescent patients with either schizophrenia or bipolar disorder and healthy controls. T2-weighted axial magnetic resonance images were used to manually define the area of the thalamus for 20 schizophrenia patients, 15 bipolar patients and 16 normal control subjects, all of whom were adolescents. Two orthogonal planned contrasts were tested: Contrast 1, patients with schizophrenia vs. patients with bipolar disorder; and Contrast 2, both patient groups taken as a single group compared to controls. Contrast 1 was not statistically significant for right or left thalamic area. Contrast 2 was statistically significant and indicated reductions in thalamic area in the patients as compared to controls. The same pattern of results emerged after adjustment for total brain volume. Our results indicate that thalamic abnormalities reported in adult schizophrenic and bipolar patients are also observed in adolescent patients. Our findings also add to the evidence implicating the thalamus in the pathophysiology of schizophrenia and bipolar disorder.

Adolescent↗
PubMed1999

An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects.

BACKGROUND: There are few imaging studies in adolescent patients with either schizophrenia or bipolar disorder. Such studies are of interest because adolescents may have a more severe illness and neurodevelopmental events may have a greater role in their pathophysiology. METHODS: We compared 20 patients with schizophrenia and 15 patients with bipolar disorder (10 to 18 years) to 16 normal adolescents on magnetic resonance imaging (MRI) measures of intracranial volume and ventricular and sulcal enlargement. Two planned comparison contrasts were employed, one comparing the two patient groups to each other (contrast 1), and one comparing both patient groups combined to control subjects (contrast 2). RESULTS: None of the contrast 1 comparisons (schizophrenia vs bipolar) were statistically significant. Contrast 2 comparisons (control subjects vs patients) were statistically significant for intracranial volume (reduced in patients) as well as frontal and temporal sulcal size (increased in patients). CONCLUSIONS: The patient groups were not statistically significantly different from each other on any measure. The combined patient groups were different from control subjects on intracranial volume and frontal and temporal sulcal size. Also, there was evidence for ventricular enlargement, after removal of a control subject with an extreme value. These findings indicate that the same abnormalities noted in adult populations are present in adolescents.

Adolescent↗
PubMed1999

Risperidone-induced hepatotoxicity in children and adolescents? A chart review study.

Risperidone is an atypical antipsychotic drug that has been used in the treatment of numerous psychiatric disorders in children and adolescents. The question of whether risperidone-induced weight gain is associated with steatohepatitis has recently been raised. The purpose of this chart review was to ascertain: (1) the rate of liver dysfunction observed during risperidone treatment in children and adolescents; and (2) the clinical factors associated with liver dysfunction. For purposes of this chart review study, abnormal liver function was defined by serum transaminase or bilirubin values falling outside the normal laboratory ranges. Chart reviews were completed on 38 youths with ages ranging from 5-17 years with a variety of psychiatric diagnoses. The mean length of risperidone treatment was 15.2 months at a mean dose of 2.5 mg/day. It was found that 37 of the 38 youths treated with risperidone had no liver enzyme abnormalities at the end of study. One subject had an alanine aminotransferase (ALT) level of 46 U/L which was 7 U/L above the upper limit of normal for this laboratory test. This isolated value was not considered clinically significant. These data were noted in spite of weight gain and the use of numerous concomitant psychotropic medications. These findings suggest that risperidone in short term treatment does not commonly lead to evidence of abnormal liver function at therapeutic doses in children and adolescents. Larger-scale, prospective studies are needed in order to confirm these findings.

Adolescent↗
PubMed1999

Differential effectiveness of methylphenidate and Adderall in school-age youths with attention-deficit/hyperactivity disorder.

OBJECTIVE: To compare the effectiveness of a single dose of Adderall (q.d.) with that of 2 daily doses of methylphenidate (b.i.d.; MPH) as a treatment for attention-deficit/hyperactivity disorder (ADHD) in youths ranging in age from 5 to 17 years. Forty-two youths treated with MPH were compared with 42 youths treated with Adderall. Subjects were matched for age, sex, and DSM-IV diagnostic subtype. METHOD: Youths were assigned to the Adderall or MPH condition by their prescribing physician. All youths were evaluated under 5 conditions, including baseline, placebo, 5 mg, 10 mg, and 15 mg. The best dose was assigned prior to breaking the medication blind and was assigned by the consensus of the psychologist and psychiatrist. Subjective ratings by both teachers and parents were examined for dosage level effects and medication type effects. RESULTS: Best dose was always superior to baseline and placebo conditions. No differences between MPH and Adderall were observed on either teacher or parent ratings of behavior. CONCLUSIONS: Both MPH and Adderall have been shown to be effective treatments for children with ADHD. Both medications appear to improve teachers' and parents' ratings of behavior. Single-dose treatments of Adderall appear to be as effective as 2 daily doses of MPH and therefore increase the possibility of managing treatment without involving the school in medication administration. In addition, youths who have previously been unsuccessfully treated with MPH because of adverse side effects or poor response may be successfully treated with Adderall.

Adolescent↗
PubMed1999

Paroxetine pharmacokinetics in depressed children and adolescents.

OBJECTIVE: To describe the pharmacokinetics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics. METHOD: Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol-O-methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements. RESULTS: There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 +/- 5.2 (SD) hours. The average clearance was 88.7 +/- 66.4 mL/min/kg. The mean area under the plasma drug concentration curve was 0.09 +/- 0.10 microgram/mL.hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted. CONCLUSIONS: Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients.

Adolescent↗