Sertraline Treatment of Children and Adolescents With Obsessive‐Compulsive Disorder or Depression: Pharmacokinetics, Tolerability, and Efficacy

Alderman, Jeffrey; Wolkow, Robert; Chung, Mun Su; Johnston, Hugh F.

doi:10.1097/00004583-199804000-00016

Cited by 113 publications

(51 citation statements)

References 21 publications

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“…Although oral clearance and volume of distribution increased with both age and weight, normalization for weight abolished the effect of age. This suggests that, as is the case for many drugs (Crom, 1994), including other SSRIs such as sertraline (Alderman et al, 1998) and fluoxetine (Wilens et al, 2002), weight may be the more important determinant of paroxetine PK in the pediatric population. No discernible effect of sex on PK parameters was evident.…”

Section: Discussionmentioning

confidence: 98%

Multiple Dose Pharmacokinetics of Paroxetine in Children and Adolescents with Major Depressive Disorder or Obsessive–Compulsive Disorder

Findling

Nucci

Piergies³

et al. 2005

Neuropsychopharmacol

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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 (0À24) 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 (po0.0001), 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.

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Section: Discussionmentioning

confidence: 98%

Multiple Dose Pharmacokinetics of Paroxetine in Children and Adolescents with Major Depressive Disorder or Obsessive–Compulsive Disorder

Findling

Nucci

Piergies³

et al. 2005

Neuropsychopharmacol

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“…Compartmental models are usually derived by solving a series of ordinary differential equations, and error terms are incorporated into the model to account for any systematic or natural variation that may be present in the data. PK studies are often interested in measures, such as the area under the concentration-time curve (AUC), maximum concentration (C max ), time of maximum concentration (t max ), elimination half-life (t 1/2 ), clearance rate (CL) and the volume of the distribution (V) (e.g., [14][15][16][17]). …”

Section: Design Of Pharmacokinetic Studiesmentioning

confidence: 99%

“…Pharmacologists are often interested in determining the maximum concentration of a drug (C max ) in patients during PK studies to ensure that patients are not exposed to toxic concentrations (e.g., [14,16,17]). Here, our parameter of interest, φ , is the peak concentration estimate C max , which occurs at the time when the infusion of the drug is complete (i.e., when t = T in f ).…”

Section: Posterior Precision Of the Peak Concentration Estimatementioning

confidence: 99%

“…Pharmacologists are also interested in estimating the AUC for concentration-time curves to determine the patients' total exposure to a drug (e.g., [14][15][16][17]). To enable an analytic solution to be found for the precision of the posterior distribution of this parameter of interest (when using Laplace approximations to approximate the posterior distribution), we decided to instead look at the log AUC, which was closer to being normally distributed a priori than the (non-transformed) AUC.…”

Section: Posterior Precision Of the (Log) Auc Estimatementioning

confidence: 99%

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Fully Bayesian Experimental Design for Pharmacokinetic Studies

Ryan

Drovandi

Pettitt

2015

Entropy

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Utility functions in Bayesian experimental design are usually based on the posterior distribution. When the posterior is found by simulation, it must be sampled from for each future dataset drawn from the prior predictive distribution. Many thousands of posterior distributions are often required. A popular technique in the Bayesian experimental design literature, which rapidly obtains samples from the posterior, is importance sampling, using the prior as the importance distribution. However, importance sampling from the prior will tend to break down if there is a reasonable number of experimental observations. In this paper, we explore the use of Laplace approximations in the design setting to overcome this drawback. Furthermore, we consider using the Laplace approximation to form the importance distribution to obtain a more efficient importance distribution than the prior. The methodology is motivated by a pharmacokinetic study, which investigates the effect of extracorporeal membrane oxygenation on the pharmacokinetics of antibiotics in sheep. The design problem is to find 10 near optimal plasma sampling times that produce precise estimates of pharmacokinetic model parameters/measures of interest. We consider several different utility functions of interest in these studies, which involve the posterior distribution of parameter functions.

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“…The explanations are interesting. In one paper by Alderman and his colleagues, the authors decided to only publish side effects that occurred in 10% or more of the patients, which excused them from reporting the fact that 9% of the children on Zoloft in their study had engaged in a suicidal act (Alderman, Wolkow, Chung, & Johnston, 1998;Healy, 2003a).…”

Section: Zoloft (Sertraline)mentioning

confidence: 99%

The SSRI Trials in Children: Disturbing Implications for Academic Medicine

Leo

2006

Ethical Hum Psychol Psychiatry

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The recent announcement by the Food and Drug Administration (FDA) requiring pharmaceutical companies to warn patients about the increased likelihood of suicidal thoughts when taking antidepressants was largely due to the recent availability of data that had gone unreported in the original research reports. The current article is a summary of the comparison between the published literature and the recently released data available on the FDA web site, with a focus on Prozac, Paxil, and Zoloft. The discrepancies between the two versions suggest that the scientific community was not given enough information in the published medical literature to make adequately informed decisions about the optimal method for treating emotionally distressed children. There are many voices that want to blame the FDA for its role in the widespread use of these medications. The current article focuses on the role that academic medicine, played in the process whereby these medications became so widely accepted.

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Sertraline Treatment of Children and Adolescents With Obsessive‐Compulsive Disorder or Depression: Pharmacokinetics, Tolerability, and Efficacy

Cited by 113 publications

References 21 publications

Multiple Dose Pharmacokinetics of Paroxetine in Children and Adolescents with Major Depressive Disorder or Obsessive–Compulsive Disorder

Multiple Dose Pharmacokinetics of Paroxetine in Children and Adolescents with Major Depressive Disorder or Obsessive–Compulsive Disorder

Fully Bayesian Experimental Design for Pharmacokinetic Studies

The SSRI Trials in Children: Disturbing Implications for Academic Medicine

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