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Biomedical subjects

B Geller

Publications and source records attributed to B Geller.

At least 19 recordsLinked to original sources
PubMed1992

Early findings from a pharmacokinetically designed double-blind and placebo-controlled study of lithium for adolescents comorbid with bipolar and substance dependency disorders.

1. This manuscript reports the early findings from a National Institute on Drug Abuse funded study of lithium for adolescents dually diagnosed with bipolar and substance dependency disorders. The authors elected to publish early findings in the hope that it would accomplish a twofold mission. 2. The first part would be to encourage other investigators to participate in research in this area and the second would be to heighten the awareness of clinicians that adolescents presenting with either one of these disorders might also have the other. 3. The early findings demonstrated the feasibility of recruiting, retaining and monitoring this complex population on an outpatient basis. 4. Steady-state serum lithium levels were pharmacokinetically placed in the study range, 0.9-1.3 mEq/L. Preliminary results are encouraging in finding lithium more effective than placebo for alleviating both the substance dependency and the mood disordered symptomatology. 5. The characteristics of the study population to date have been chronicity of both disorders, impairment in the severe range in multiple areas of functioning, and strong family histories for both affective and substance use disorders. The substance dependency was to both alcohol and marijuana; but all subjects also had marked polydrug abuse. 6. In order to best monitor lithium compliance and drug/alcohol use during protocol, randomly timed weekly serum and urine assays were obtained. 7. The implications of these early findings for the outcome of this acute phase study and for the development of longitudinal treatment strategies are discussed.

Adolescent↗
PubMed1992

Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major depressive disorder.

A random assignment, double-blind, placebo-controlled study of nortriptyline in 50 prepubertal 6- to 12-year-olds with Research Diagnostic Criteria and DSM-III major depressive disorder was performed. The protocol included a 2-week placebo wash-out phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level pharmacokinetically placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level 24 hours after a single dose administered at baseline. The mean plasma level was 89.9 ng/ml. The study population was severely depressed, had a chronic, unremitting course of long duration before the study, had a high percentage of family histories with affective disorder, alcoholism and suicidality, and had a high rate of comorbidity. None of the subjects had ever received tricyclic antidepressants before this study. There was a poor rate of response in both treatment groups (30.8% active, 16.7% placebo). Active subjects did not evidence the anticholinergic side effects reported in adult samples. The implications of these findings for future pharmacotherapy studies of depressed children are discussed.

Child↗
PubMed1992

Baseline and 2- to 3-year follow-up characteristics of placebo-washout responders from the nortriptyline study of depressed 6- to 12-year-olds.

Data are presented on the baseline characteristics and 2- to 3-year follow-up assessments of placebo-washout responders (PWRs) from a previously reported pharmacokinetically designed double-blind placebo-controlled trial of nortriptyline for major depressive disorder in 6- to 12-year-olds. Eleven of the 12 PWRs consented to participate in the follow-up study. At baseline, the only significant difference between the PWRs and the non-PWR subjects was that more females were PWRs. Notably, there were no significant differences with respect to severity, chronicity, age of onset, or comorbid psychopathology. The follow-up assessments showed that the rate of relapse to major depressive disorder and the rate of development of bipolarity were not significantly different for PWRs compared with non-PWRs. The authors discuss these findings vis-à-vis the adult literature and provide recommendations for the use of placebo-washout phases in future double-blind, placebo-controlled psychopharmacology trials in children.

Bipolar Disorder↗
PubMed1992

Lithium and tricyclic antidepressants.

Pharmacokinetic studies of lithium and tricyclic antidepressants (TCAs) in children and adolescents report similarities to adults with respect to a wide interindividual genetic variation in the rate of elimination and with regard to the linear nature of the system. Children may eliminate these medications more rapidly; therefore, more frequent dosing may be necessary to maintain steady state serum lithium or plasma TCA levels. Doses of these medications necessary for desired blood levels can be obtained from tables based on nomograms (i.e., one-step dosage adjustment determined from a single serum lithium or plasma TCA level drawn 24 hours after administration of a single dose). Use of these dose prediction tables avoids toxicity due to excessively high blood levels in genetically slow metabolizers in whom medication regimes that use mg/kg dose schedules may produce toxic blood levels.

Adolescent↗
PubMed1991

Psychopharmacology of children and adolescents: pharmacokinetics and relationships of plasma/serum levels to response.

This article reviews data from the literature on pharmacokinetics and on relationships of plasma/serum levels to response in the child and adolescent population. The following topics will be covered: saliva vs. serum monitoring, drug-drug interactions, enzyme induction, and the effect of febrile illnesses on protein binding. Similarity of elimination processes based on manifestations that are genetically determined across age groups will be contrasted to elimination mechanisms that are different for the pediatric group due to age specific developmental considerations. Age related differences in plasma/serum level response relationships will be discussed with respect to study population characteristics and pharmacodynamic implications.

Adolescent↗
PubMed1990

Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a "fixed plasma level" design.

We performed a random assignment, double-blind, placebo-controlled study of nortriptyline (NT) in postpubertal 12- to 17-year-olds with Research Diagnostic Criteria (RDC) and DSM-III major depressive disorder. The protocol included a 2-week placebo washout phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level drawn 24 hours after a single dose administered at baseline. The study population was severely depressed and had a chronic, unremitting course prior to study; a high percentage of family histories with affective disorder, alcoholism, and suicidality; and a high rate of comorbidity. Of the 52 subjects enrolled, there were 17 placebo washout responders, 4 dropouts, and 31 completers (12 active and 19 placebo). Only one active subject responded; therefore, the study was terminated early. The mean NT plasma level was 91.1 (18.3 SD) ng/ml. The two treatment groups had similar postprotocol severity ratings. Subjects on active drug did not evidence the anticholinergic side effects reported in adult samples. The negative outcome in this study is similar to the findings in our previously reported NT study in prepubertal 6- to 12-year-olds.

Adolescent↗
PubMed1987

Prospective study of scheduled withdrawal from nortriptyline in children and adolescents.

Thirty 6- to 16-year-old subjects were gradually tapered from their maintenance dose of nortriptyline while being monitored for withdrawal effects. Five subjects had brief gastrointestinal distress that did not require the administration of an extra dose. The results of this open study suggest that scheduled tapering of nortriptyline will preclude withdrawal symptoms in most pediatric patients.

Adolescent↗
PubMed1987

Child and adolescent nortriptyline single dose pharmacokinetic parameters: final report.

This is the final report of a study of single dose pharmacokinetic parameters of nortriptyline in children and adolescents 5 to 16 years old (N = 64). The data were analyzed separately for the 5- to 12-year-olds (N = 41) and for the 13- to 16-year-olds (N = 32). The results confirm the preliminary findings of the similarity of the pharmacology of nortriptyline between the pediatric and adult age groups with respect to a logarithmically linear rate of elimination and a wide interindividual rate of metabolism. The 5- to 12-year-olds had a significantly shorter mean half-life and a significantly greater mean apparent oral clearance than the 13- to 16-year-olds. The mean half-life in the 5- to 12-year-olds was 20.8 +/- 7.2 (range, 11.2 to 42.5) hours and in the 13- to 16-year-olds was 31.1 +/- 19.8 (range, 14.2 to 89.4) hours. A twice a day dosage regimen is recommended for the entire 5- to 16-year-old group based on their range of half-lives.

Adolescent↗
PubMed1986

Preliminary data on the relationship between nortriptyline plasma level and response in depressed children.

Twenty-two subjects 6-12 years old who met Research Diagnostic Criteria and DSM-III criteria for major depressive disorder received a fixed daily dose of nortriptyline during an 8-week protocol. Weekly plasma levels were measured; the raters performing behavioral assessments were blind to these levels. There was a highly significant difference between the mean steady-state plasma levels and the milligram-per-kilogram doses of the responders and nonresponders. The data suggest that the lower limit of the therapeutic range of nortriptyline in children (over 60 ng/ml) is similar to that reported for adults. The disadvantages of the use of a milligram-per-kilogram dose rather than a pharmacokinetic approach are discussed.

Age Factors↗