Population pharmacokinetics of methylphenidate in children with attention-deficit hyperactivity disorder.

Sources of individual variation in plasma methylphenidate (MP) concentrations during usual clinical use are not established. This was evaluated in a series of patients receiving clinical treatment with MP. A single plasma MP concentration was determined in each of 273 children and adolescents ages 5 to 18 years (mean: 11.1 years) who were clinically good responders to MP for the treatment of attention-deficit hyperactivity disorder. MP was given on a twice-daily schedule (mean dose: 25 mg/day) in 40% of patients and three times daily (mean dose: 39.3 mg/day) in 60%. A nonlinear regression model was applied to estimate overall population values of MP clearance and elimination half-life (t1/2), assuming a one-component model with first-order absorption and elimination, and further assuming that clearance is linearly related to body weight. The model incorporated each patient's dosage size and schedule, body weight, and time of the plasma sample. Iterated solutions of best fit were: t1/2, 4.5 hours (95% confidence interval [CI]: 3.1-8.1 hours), and apparent clearance, 90.7 ml/min/kg (95% CI: 74.6-106.7 ml/min/kg). The model explained 43% of the overall variance in MP concentrations (r2 = 0.43, p < .001). In a small subsample (N = 16), a second plasma sample was drawn at the same time of day and at the same dose; the correlation between the two concentration values was 0.83. The relatively noninvasive approach used in this study allows the assessment of pharmacokinetic properties of medications under conditions of appropriate clinical use in special populations such as children, adolescents, and the elderly.

Characteristics of children and adolescents in a psychiatric hospital and a corrections facility.

Popular opinion holds that youngsters in corrections programs are delinquents in need of reform, whereas youngsters in psychiatric settings have mental health problems and need therapy. Yet some literature suggests that youth in the two settings may not differ greatly in their mental health status. The authors compared demographic, emotional, and behavioral characteristics of youngsters placed in public psychiatric hospital and corrections settings, and they found few differences. Child Behavior Checklist scores for social competence and total problems were high and quite similar for youngsters in the two settings. White children scored significantly worse than black children on Child Behavior Checklist Internalizing, Externalizing, and total problems in corrections settings but not in the psychiatric hospital. Moreover, race was the only variable that predicted the site in which youth were placed. The findings suggest a need to study (1) the mental health needs of youngsters in nonmental health settings and (2) the procedures by which youth are assigned to service settings.

Ten cases of head-injured, suicide-surviving adolescents: challenges for rehabilitation.

This paper describes ten adolescents who made unequivocal suicide attempts which resulted in near-death and brain damage. As predicted from studies of successful suicide, this group was mostly male, in late adolescence, and with histories of psychiatric difficulties. The fact that each had tried to commit suicide was avoided by the medical care facilities and by the families. The term 'accident' was customary. This paper makes suggestions for mental health clinicians who consult to head-injury rehabilitation teams treating such adolescents. Two cases are presented to highlight the findings and recommendations of this study.

Control-related cognitions and depression among inpatient children and adolescents.

In previous studies, children with numerous depressive symptoms have shown two patterns of control-related cognition: (1) low levels of perceived personal competence, and (2) "contingency uncertainty"--confusion regarding the causes of significant events. The generality of these findings was tested for more seriously disturbed children. Three child inpatient samples, from separate psychiatric hospitals, completed the Children's Depression Inventory (CDI) plus measures of control-related beliefs. In all three samples, the findings resembled those of previous studies: CDI scores were significantly related to low perceived competence and to contingency uncertainty; by contrast, CDI scores were only weakly related to perceived noncontingency. The findings suggest that depressive symptoms in children may be (1) more closely linked to "personal helplessness" than to "universal helplessness," and (2) more closely linked to uncertainty about the causes of events than to firm beliefs in noncontingency. The findings carry implications for etiology and treatment of child depression.

Lithium-induced nephrotic syndrome.

The nephrotic syndrome is a rare, idiosyncratic adverse renal effect of lithium that can occur with therapeutic plasma lithium levels. The syndrome is usually reversed by discontinuation of lithium treatment but may require corticosteroids. Renal biopsies reveal fusion of the foot processes of renal epithelial cells, referred to as "minimal change disease." No particular variable identifies individuals at risk for developing the nephrotic syndrome while taking lithium. The authors review the eight published cases in the English-language literature and present the case of an adolescent who developed lithium-induced nephrotic syndrome.

Carbamazepine-lithium toxicity in brain-damaged adolescents.

For several years carbamazepine has been used to treat intractable mania and it is frequently used in combination with lithium. Reports of toxicity have appeared in the past 2 years and some risk factors have been suggested. This paper reports four cases of brain-damaged adolescents treated with carbamazepine and lithium for both seizure and behaviour control who developed this reported neurotoxic phenomenon.

Neuropsychiatric interventions with head injured children and adolescents.

With increasing numbers of surviving head injured children and adolescents, there is a growing need to provide child neuropsychiatric services as a necessary component for their comprehensive rehabilitation. This paper discusses the critical role child psychiatry should have in pediatric head injury rehabilitation and outlines a framework for neuropsychiatric interventions including the use of neuropsychoactive medications. Case examples highlight the principles and practicalities of interventions.