Biomedical subjects

Regan Fong

Publications and source records attributed to Regan Fong.

6 recordsLinked to original sources

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

Analysis of electrocardiographic data following use of paroxetine in pediatric depression and obsessive-compulsive disorder.

OBJECTIVE: This retrospective analysis of electrocardiographic (ECG) data investigated the cardiovascular effects of paroxetine 10-50 mg/day in pediatric patients (7-18 years of age). Data were collected from three 8- to 10-week, randomized, placebo-controlled, double-blind trials of paroxetine in pediatric patients with major depressive disorder or obsessive-compulsive disorder. METHOD: Electrocardiograms (ECGs) were retrospectively retrieved from 63 study sites in the United States and Canada. Only patients with at least one screening and one on-treatment ECG were included. ECGs were analyzed for heart rate, QT interval corrected using Bazett's formula (QTcB) and Fridericia's formula (QTcF), at screening and while being treated. PR, R-R, and QRS intervals and the maximum change in QTcB and QTcF from screening to endpoint were determined. Clinically significant thresholds were defined a priori. RESULTS: A total of 1,451 ECGs from 449 patients receiving placebo (n = 207), paroxetine (n = 200), or imipramine (n = 42) were analyzed. Treatment with paroxetine did not significantly increase QTcB or QTcF or any ECG parameters compared with placebo. Treatment with imipramine significantly increased heart rate and QTcB, R-R, and QRS intervals compared with either paroxetine or placebo. CONCLUSIONS: Data from this retrospective study indicate that paroxetine (10-50 mg/day) is unlikely to be associated with significant ECG changes in medically healthy pediatric patients.

Adolescent↗

PubMed2006

Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. METHOD: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating Scale-Revised total score at week 8 last observation carried forward). Safety was primarily assessed by spontaneous reporting of adverse events. RESULTS: A total of 206 patients (intent to treat) were randomized to paroxetine (n = 104) or placebo (n = 102). Week 8 Children's Depression Rating Scale-Revised total score adjusted mean changes from baseline for patients receiving paroxetine and placebo were -22.58 (SE 1.47) and -23.38 points (SE 1.60), respectively (0.80, 95% confidence interval -3.09 to 4.69, p = 0.684). Increased cough (5.9% versus 2.9%), dyspepsia (5.9% versus 2.9%), vomiting (5.9% versus 2.0%), and dizziness (5.0% versus 1.0%) occurred in >or=5% of the paroxetine group and at least twice that of the placebo group. Six of 104 (5.8%) paroxetine patients reported serious adverse events compared to 1 placebo patient (1.0%). The incidence of adverse events of suicidal behavior and/or ideation while taking study medication (excluding taper) was 1.92% (2/104) for paroxetine versus 0.98% (1/102) for placebo. CONCLUSIONS: Paroxetine was not shown to be more efficacious than placebo for treating pediatric major depressive disorder.

Adolescent↗

PubMed2003

Event-related brain potentials during auditory and visual word recognition memory tasks.

Event-related brain potentials (ERPs) recorded during presentation of a series of words or pictures show enhanced positivity between 300 and 800 ms after presentation of repeated items. However, little attention has been directed to the characterization of this ERP recognition memory effect using auditory stimuli. The present study directly compared the ERP 'old/new effect' for words presented in the visual and auditory modalities. Nose-referenced ERPs were recorded from 30 electrode sites while participants (N=16) were engaged in visual and auditory continuous word recognition memory tasks. Spatially and temporally overlapping ERP components were identified and measured by covariance-based principal components analysis. The expected old/new effect was observed in both modalities, with a comparable time course peaking at 560 ms, but having a more anterior scalp topography for visual items. This suggests a common cognitive process (i.e. successful retrieval of information from memory) associated with separable neural generators in each modality. Despite this temporal synchronization, the old/new effect overlapped ERP components having distinct scalp topographies (N2) or peak latencies (P3) for each modality. The positive-going old/new effect was preceded by an earlier negativity peaking at 370 ms that was greater across modalities for old than new words, likely reflecting semantic processing aspects of word recognition memory. A late (beyond 900 ms), broadly-distributed negativity was also greater for old than new words, prolonged for auditory items, and may represent activity of a post-retrieval process.

Acoustic Stimulation↗

PubMedDate not supplied

An international, multicenter, placebo-controlled trial of paroxetine in adolescents with major depressive disorder.

OBJECTIVE: The aim of this study was to examine the efficacy, safety, and tolerability of paroxetine in adolescents with unipolar major depression. METHOD: Two hundred eighty-six (286) adolescents with unipolar major depression were randomly assigned to receive either paroxetine or placebo for 12 weeks. RESULTS: The proportion of Montgomery-Asberg Depression Rating Scale (MADRS) responders (at least 50% reduction from baseline) for paroxetine and placebo were similar and not statistically different at endpoint (p = 0.702). A similar result was obtained for change from baseline on the Kiddie-Schedule for Affective Disorders and Schizophrenia for School- Age Children (K-SADS-L) depression subscale. Among secondary endpoints, only a significantly higher Clinical Global Impression-Improvement (CGI-I) response rate was reported in paroxetine-treated patients versus placebo (69.2% versus 57.3%; p = 0.045). In general, results differed by age, with patients older than 16 years demonstrating a greater response to active treatment. This age group also reported more adverse experiences (AEs) relative to placebo than younger adolescents. Overall, paroxetine was generally well tolerated (11% discontinued owing to an AE versus 7% of placebo-treated patients). A post hoc analysis of AEs related to suicidal behavior suggested a greater incidence of these events for paroxetine than for placebo (4.4% versus 2.1%); however, this difference was not statistically significant (odds ratio, 2.15, 95% Confidence Interval 0.45, 10.33; p = 0.502). CONCLUSIONS: No statistically significant differences were observed for paroxetine compared with placebo on the two prospectively defined primary efficacy variables. Paroxetine at 20-40 mg/day administered over a period of up to 12 weeks was generally well tolerated.

Adolescent↗

PubMedDate not supplied

Evaluation of suicidal thoughts and behaviors in children and adolescents taking paroxetine.

OBJECTIVE: The aim of this study was to summarize results of a blinded review of potential suicidal events and analyses comparing incidence rates between paroxetine- and placebo-treated pediatric patients. METHOD: One thousand one hundred ninety-one (1191) children and adolescents received paroxetine (n = 642) or placebo (n = 549) during placebo-controlled portions of all acute double-blind trials of paroxetine (n = 5). An expert panel blindly reviewed and categorized all identified cases detected by electronic and manual search of adverse events (AEs), serious AEs, and selected cases as suicidal or non-suicidal behavior. Incidence rates were calculated for suicide-related events and for rating scale items assessing suicidality. RESULTS: Suicide-related events occurred more often in paroxetine (22 of 642, 3.4%) than placebo groups (5 of 549, 0.9%); odds ratio (OR) 3.86 (95% CI 1.45, 10.26; p = 0.003). All suicide-related events occurred in adolescents of at least 12 years, except for 1 of 156 paroxetine-treated children. All suicide attempts occurred in major depressive disorder (MDD); few suicide-related events occurred in patients with a primary anxiety disorder. Suicide item analyses did not reveal significant differences between paroxetine and placebo. CONCLUSIONS: Adolescents treated with paroxetine showed an increased risk of suicide-related events. Suicidality rating scales did not show this risk difference. The presence of uncontrolled suicide risk factors, the relatively low incidence of these events, and their predominance in adolescents with MDD make it difficult to identify a single cause for suicidality in these pediatric patients.

Adolescent↗