Magda Campbell

Lithium in Hospitalized Aggressive Children with Conduct Disorder: A Double-Blind and Placebo-Controlled Study

OBJECTIVE To assess critically the efficacy and safety of lithium and replicate earlier findings in a larger sample of aggressive children with conduct disorder and to assess the utility of the Profile of Mood States (POMS) in this population. METHODS Children hospitalized for treatment-refractory severe aggressiveness and explosiveness and with diagnosed conduct disorder were subjects in this double-blind, placebo-controlled clinical trial. After a 2-week placebo baseline period, children were randomly assigned to lithium or placebo treatment for 6 weeks of placebo. The main outcome measures were the Global Clinical Judgments (Consensus) Scale, Childrens Psychiatric Rating Scale, Conners Teacher Questionnaire, Parent-Teacher Questionnaire, and the POMS. RESULTS Fifty children (mean age 9.4 years) completed this study. The mean optimal daily dose of lithium was 1,248 mg and the mean serum level was 1.12 mEq/L. Lithium was superior to placebo, although the effects on some measures were more modest than in a previous study. CONCLUSIONS Lithium appears to be an effective treatment for some severely aggressive children with conduct disorder. Although the POMS appeared to be reliable, it did not detect any response to lithium.

Neuroleptic-Related Dyskinesias in Autistic Children: A Prospective, Longitudinal Study

OBJECTIVE To report results from a long-term prospective study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias. METHOD Subjects were children with autism requiring pharmacotherapy for target symptoms. After baseline assessments, children received haloperidol treatment; responders requiring further treatment were considered for enrollment into the present study. Six-month haloperidol treatment periods were followed by a 4-week placebo period. The procedure was repeated if further haloperidol treatment was required. At specified times children were evaluated by using multiple instruments. RESULTS Between 1979 and 1994, 118 children aged 2.3 to 8.2 years participated in the study. The mean dose of haloperidol was 1.75 mg/day. Mainly withdrawal dyskinesias (WD) developed in 40 (33.9%) children; 20 had more than one dyskinetic episode. A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidenced a significantly higher incidence of WD. Occurrence rates of tardive dyskinesia (TD) and multiple episodes of TD/WD were higher among girls. CONCLUSION Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias; greater cumulative haloperidol dose and/or longer exposure to haloperidol may increase the risk.

A Comparison of Haloperidol and Behavior Therapy and Their Interaction in Autistic Children

Abstract Haloperidol and behavior therapy, and the interaction of the two treatments were critically assessed with respect to their effects on symptoms and language acquisition in 40 autistic children aged 2.6 to 7.2 years. The children were randomly assigned to four treatment groups in a factorial design. The study was placebo controlled and double-blind, using multiple independent raters who assessed treatment effects under three types of rating conditions. Haloperidol was found to be significantly superior to placebo in decreasing certain symptoms, depending on the age group. The combination of the two treatments was most effective in facilitating the acquisition of imitative speech. Optimal dosage of haloperidol ranged from 0.5 to 4.0 mg./day; the most common untoward effect was excessive sedation, which was clearly a function of dosage.

The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children

This double-blind and placebo-controlled clinical trial in autistic children had three objectives: (a) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms; (b) to further assess its safety when given on a short-term basis: and (c) to assess whether it has an effect on discrimination learning. Forty-five children, 2.02 to 7.58 years old (M=4.49), completed this crossover design, with random assignment to treatment sequences. Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects; at doses ranging from 0.25 to 4.0 mg/day (M=0.844), there was a clinically and statistically significant reduction of a variety of symptoms. Under the given conditions, the children failed to learn on either haloperidol or placebo.

Naltrexone in Autistic Children: Behavioral Symptoms and Attentional Learning

OBJECTIVE To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.

Psychopharmacology in Child and Adolescent Psychiatry: A Review of the Past Five Years

Abstract A review of developments in child and adolescent psychopharmacology in the past 5 years reveals progress in the investigation of a variety of disorders. The psychopharmacology of major diagnostic categories is reviewed, with discussion of available study results and comment upon promising areas for future investigation. Many questions still are unanswered about the efficacy and safety of various medications. A dearth of data persists regarding optimal drug choices for treating such illnesses as schizophrenia and depression, reflecting the need for classification of underlying biochemical abnormalities and additional studies of phenomenology. Similarly, some agents are still commonly used purely on an empirical basis because of their clinical value.

Carbamazepine in Aggressive Children with Conduct Disorder: A Double-Blind and Placebo-Controlled Study

OBJECTIVE To assess critically the short-term efficacy and safety of carbamazepine in the reduction of aggressiveness in children with diagnosed conduct disorder. METHOD Subjects were children aged 5 to 12 years who were hospitalized for treatment-resistant aggressiveness and explosiveness and who had diagnosed conduct disorder. The study was double-blind and placebo-controlled, using a parallel-groups design. Following a 2-week placebo baseline period, children who met the aggression criteria were randomly assigned to treatments for 6 weeks; the study ended with a 1-week posttreatment placebo period. Multiple raters rated the children independently, using multiple rating scales under four conditions. The main outcome measures included the Overt Aggression Scale, the Global Clinical Judgments (Consensus) Scale, and the Childrens Psychiatric Rating Scale. RESULTS Twenty-two children, aged 5.33 to 11.7 years, completed the study. Carbamazepine was not superior to placebo at optimal daily doses ranging from 400 to 800 mg, mean 683 mg, at serum levels of 4.98 to 9.1 micrograms/mL. Untoward effects associated with administration of carbamazepine were common. CONCLUSIONS In this modest sample of children, the superiority of carbamazepine over placebo in reducing aggressive behavior was not demonstrated.

A Comparison of Schizophrenic and Autistic Children

A comparison of schizophrenic, autistic, and conduct disordered children ages 5.2 to 12.10 years is presented. Diagnosis was made by the authors in all cases using DSM-III criteria. The children were compared on a variety of variables including pre- and perinatal complications, intellectual functioning, and behavioral profile. Findings indicate that children under 12 years of age can be diagnosed schizophrenic disorder by DSM-III criteria. All schizophrenic children had a disorder of thinking and most had hallucinations (83.3%) while delusions were somewhat less frequent (54.2%). Schizophrenic children differ from autistic children on most variables although there is some overlap.

Lithium and chlorpromazine: A controlled crossover study of hyperactive severely disturbed young children

A controlled crossover study of lithium and chlorpromazine involving 10 severely disturbed children, 3 to 6 years of age, of which 6 were schizophrenic and 1 autistic, is reported in detail. Patients were matched for motor activity (hyper- and hypoactivity) and prognosis. More symptoms diminished on chlorpromazine than on lithium. However, improvements were only slight on both, except in one child whose autoaggressiveness and explosiveness practically ceased on lithium (nonblind evaluations). Blind ratings indicated no statistically significant difference between the two drugs as well as absence of statistically significant change from baseline to treatment with either. Lithium diminished the severity of individual symptoms, though not statistically significant, such as explosiveness, hyperactivity, aggressiveness, and psychotic speech. Its effect in adult schizophrenia is compared to responses of schizophrenic children. Also discussed is the relationship of EEG to clinical improvement and toxicity, and effect of lithium on hyperactivity and aggressiveness. It is suggested that lithium may prove of some value in treatment of severe psychiatric disorders in childhood involving aggressiveness, explosive affect and hyperactivity.

Response to Triiodothyronine and Dextroamphetamine: A Study of Preschool Schizophrenic Children.

A controlled study of triiodothyronine (T3), a hormone with CNS effects and stimulating properties, is reported in detail and discussed. Twelve of the 16 subjects (13 boys and 3 girls ranging in age from 3 to 6 years) were psychotic (10 schizophrenic and 2 autistic), 2 had chronic organic brain syndromes (Turners and Klinefelters, both with withdrawing reaction) and 2 were nonpsychotic (withdrawing and hyperkinetic reactions). Optimal daily doses of T3 ranged from 12.5 to 75 mcg, while those of dextroamphetamine, used as control, from 1.25 to 10 mg. Nonblind evaluations indicated marked improvement on T3 in 11 children, slight in 3, and deterioration in one. Blind ratings indicated statistically significant improvement in overall symptomatology (p⩽0.01). While dextroamphetamine yielded poor responses in all diagnostic categories, T3 had antipsychotic and stimulating effects. T3 is viewed as an agent that is potentially effective in the treatment of childhood schizophrenia.