A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures?

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.

Determinants of expressed emotion in families of disturbed and normal children.

Both high expressed emotion (EE) and psychiatric disorders were frequent in the parents of children and adolescents with disruptive behavior disorder (DBD, N = 34) and obsessive compulsive disorder (OCD, N = 49) compared to normal controls (NC, N = 41). Parental psychiatric diagnosis was significantly related to high-EE in fathers (p = .0002) and mothers (p = .0001) of all groups combined, and in parents of the ill groups (p = .03). Absence of diagnosis was associated with low-EE in fathers (p = .0006) and mothers (p = .04) of the controls. Psychiatric diagnosis was the only significant predictor for high-EE in fathers, while for mothers child's diagnosis was a stronger predictor.

Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?

The response to stimulant drugs of 48 boys with attention deficit/hyperactivity disorder was measured following dextroamphetamine, methylphenidate, and placebo in a double-blind crossover study. To distinguish lack of behavioral improvement from adverse drug effects, a day hospital setting and a wide dose range were used. Both drugs were highly and equally efficacious for the group as a whole, and frequently one drug or the other was superior for an individual child, or adverse effects occurred only on one of the stimulants. Only one of the 48 boys (2%) was discharged without the recommendation for continued stimulant drug treatment. "Nonresponse" appears to be extremely rare when both stimulants and a wide range of doses are given.

Stimulant drug treatment of hyperactivity: biochemical correlates.

To compare the effects of the stimulant drugs dextroamphetamine and methylphenidate on urinary and plasma monoamines and metabolites within the same clinical sample, thirty-one children with attention-deficit disorder with hyperactivity were treated with dextroamphetamine (up to 1.5 mg/kg/day), methylphenidate (up to 3.0 mg/kg/day), and placebo in an 11-week double-blind crossover trial. As expected, both drugs showed striking clinical efficacy, and within a subsample of the group, earlier findings were confirmed, that dextroamphetamine but not methylphenidate lowered urinary and plasma 3-methoxy-4-hydroxyphenylglycol and whole body norepinephrine turnover, and that urinary and plasma concentration of homovanillic acid was unaltered by either drug. Methylphenidate but not dextroamphetamine increased plasma norepinephrine. Urinary epinephrine and metanephrine were increased with both drugs, but this increase did not correlate significantly with clinical improvement.

Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability?

The occurrence of abnormal movements or perserverative/compulsive behaviors was noted in 34 (76%) of a group of 45 hyperactive boys during a double-blind crossover treatment trial of methylphenidate and dextroamphetamine given in a wide range of doses. These adverse effects were often subtle and transient, and they usually occurred only on one drug. There was only one case where treatment was discontinued due to the severity of the tic the subject developed during his initial treatment phase. Dextroamphetamine tended to produce more compulsive behaviors, which were also more likely to resemble clinical obsessive-compulsive disorder (OCD), than did methylphenidate. Abnormal movements and compulsive behaviors tended to co-occur on methylphenidate only; no general "Tourette-OCD diathesis" was found for this population.

Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children.

An acceleration-sensitive device was used to measure motor activity continuously through the day in 18 hyperactive boys in a day hospital program. The children received methylphenidate, dextroamphetamine, or placebo daily after breakfast and lunch in an 11-week double-blind crossover trial. Differential effectiveness of the two drugs in lowering motor activity was found. Methylphenidate significantly lowered activity measurements in a morning structured classroom and in less structured activities in the afternoon. Dextroamphetamine effects on activity were similar, although they did not differ significantly from placebo effects between 11:00 AM and noon in our classroom setting. Methylphenidate produced a greater decrement in motor activity than did dextroamphetamine between 11:00 AM and 1:00 PM. There were no significant differences in activity level between drug doses within each drug phase across the dose ranges used (for methylphenidate 0.45 to 1.25 mg/kg given twice daily, and for dextroamphetamine 0.2 to 0.6 mg/kg given twice daily). Plasma drug concentrations did not correlate with decrements in activity for either drug.

Fenfluramine and dextroamphetamine treatment of childhood hyperactivity. Clinical and biochemical findings.

Twenty boys (mean age, 9 +/- 2 years) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate (0.5 mg/kg/d), fenfluramine hydrochloride (0.6 mg/kg/d increased to 2.0 mg/kg/d), and placebo in a double-blind, random-order, crossover design. Half the boys also met criteria for conduct disorder. Dextroamphetamine produced immediate and marked improvement in disruptive, overactive behaviors. Fenfluramine had no effect on any behavioral measure at either the low or high dosage. Both drugs decreased levels of urinary norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid. Fenfluramine, however, also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels. It reduced urinary epinephrine levels as well, an effect opposite to that of dextroamphetamine. These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylmandelic acid. Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels. Despite the structural similarity of the two drugs, some common overall effects on catecholamine metabolism, and similar effects on weight, fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine.