Mary Anne Delaney

The working alliance and consumer case management

The Working Alliance Inventory was used to measure the strength of the therapeutic relationship between seriously mentally disabled case management clients and their case managers in a randomized trial of consumer-provided case management services. It was found that while there was no difference in the strength of the alliance between the consumer and nonconsumer teams of case managers, there were positive relationships between alliance and some outcomes, including quality of life, symptomatology, attitudes toward medication compliance, and satisfaction with mental health treatment.

Olanzapine versus haloperidol in children with autistic disorder : An open pilot study

OBJECTIVES Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment. METHOD In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Childrens Psychiatric Rating Scale (CPRS). RESULTS Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain. CONCLUSIONS The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.

Risperidone treatment in children and adolescents with autism: short- and long-term safety and effectiveness.

OBJECTIVE Atypical neuroleptics, including risperidone, are used to treat children with autism, despite limited efficacy and safety data. Many clinicians believe that risperidone will not induce dyskinesias in children. The authors investigated open risperidone treatment in children with autism and included findings on dyskinesias. METHOD The sample included 22 outpatients (mean age = 7.1 years) diagnosed with autism (DSM-IV). Treatment consisted of a 1-month short-term phase followed by a 6-month long-term phase. At the end of the long-term phase, drug was discontinued, and the need for further drug treatment and the occurrence of withdrawal dyskinesias were assessed. Measures included the Clinical Global Impressions (CGI), Childrens Psychiatric Rating Scale (CPRS), and the Abnormal Involuntary Movement Scale. RESULTS The mean risperidone dosage was 1.2 mg/day. Overall, the children had significant clinical improvement as assessed by the CPRS and CGI. Untoward effects included sedation, increased appetite, and weight gain. Two of 13 (15.4%) children treated long-term developed mild, reversible withdrawal dyskinesias when risperidone was discontinued. No child developed dyskinesias on risperidone. CONCLUSIONS Risperidone shows promise as a treatment in autism. However, withdrawal dyskinesias were noted. Further assessment of the risk of risperidone-related dyskinesias is indicated.

Ziprasidone in Adolescents with Autism: An Open-Label Pilot Study

INTRODUCTION The antipsychotic drugs are the best-studied agents shown to reduce symptoms in autism, including hyperactivity, aggression, self-abusive behavior, temper tantrums, lability, irritability, social withdrawal, and stereotypical behaviors. However, significant weight gain has been associated with use of many atypical agents. Ziprasidone has been weight neutral in adult populations, but data from adolescents and patients with autism are sparse. However, ziprasidone administration has been associated with increases in the QTc. The purpose of this study was to collect pilot data on the efficacy and safety of ziprasidone in adolescents with autism, focusing on safety issues of weight gain and QTc. METHODS Twelve adolescents with autism (mean age 14.5 +/- 1.8 years) were treated in a 6-week open pilot study. Ziprasidone dosage ranged from 20 to 160 mg/day (mean, 98.3 +/- 40.4 mg/day). The primary efficacy measure was the Clinical Global Impressions-Improvement item (CGI-I); other efficacy measures included the Aberrant Behavior Checklist and the Childrens Psychiatric Rating Scale. RESULTS Based on the CGI-I, 9 of 12 (75%) patients were treatment responders. Ziprasidone was weight neutral, and the QTc increased by a mean of 14.7 msec. Two subjects had acute dystonic reactions. Cholesterol decreased and prolactin remained the same. CONCLUSIONS Ziprasidone shows promise as a treatment for adolescents with autism. More definitive trials are needed.

Pharmacokinetics of lithium carbonate in children

The pharmacokinetics in both serum and saliva of a single oral dose of lithium carbonate 300 mg was investigated in nine children aged 9 to 12 years. The serum and saliva concentration-time curves were parallel and biexponential, with a fast distribution phase after the peak at the second hour and a slow elimination phase starting from the 12th hour. The fast phase half-life was 6.0 +/- 1.8 hour in the serum, and 5.8 +/- 1.9 hour in the saliva. The slow phase half-life was 17.9 +/- 7.4 hour in the serum and 15.6 +/- 8.2 hour in the saliva. Lithium was 2.84 +/- 0.86 times higher in the saliva than in the serum, with a saliva/serum r coefficient of correlation of 0.93. A relatively large error was found in predicting serum levels from saliva. There were significant intersubject differences in the saliva/serum ratio, which point to the need for individual ratios in clinical use. On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.

Nonpharmacological Response in Hospitalized Children With Conduct Disorder

OBJECTIVE There is a paucity of research regarding the effects of hospitalization and/or the response to placebo in children with conduct disorder who are hospitalized for chronic and severe aggression. However, many children with this problem are hospitalized and immediately begin pharmacotherapy. In this report, the effects of hospitalization and placebo administration were examined. METHOD Subjects were forty-four children (37 males, 7 females) with conduct disorder, aged 9.83 to 17.14 years, who were hospitalized for chronic and severe aggression. This was a 4-week double-blind and placebo-controlled study with a 2-week single-blind placebo lead-in period. During the 2-week placebo baseline period, aggression was measured on a 24-hour basis, using the Overt Aggression Scale. Only subjects meeting a specific aggression criterion were randomized to the treatment period of the trial. RESULTS Of the 44 subjects enrolled, 23 (52.3%) met the aggression criteria for entering the treatment period (baseline nonresponders), while 21 (47.7%) did not (baseline responders). Thus, almost half of the subjects, while taking no active medication, benefited from the inpatient milieu/structure and/or placebo. CONCLUSION This finding has important treatment and research implications. Medication to treat aggression should not be initiated immediately upon hospitalization because improvements associated with hospitalization may be attributed inaccurately to pharmacotherapy, resulting in unnecessarily medicating children. A placebo baseline period is essential to decrease the risk of a type II error in pharmacological research concerning aggression.

Advances in Drug Treatments for Children and Adolescents with Autism and Other Pervasive Developmental Disorders

Autism is a disorder characterised by abnormalities in language and social development, and repetitive behaviours. Antipsychotics, including haloperidol and risperidone, are the most widely studied drugs for reducing symptoms in children and adolescents with autism. When administered at relatively low dosages, antipsychotics have been shown to reduce repetitive behaviours (stereotypies) and social withdrawal, as well as a number of related symptoms, such as hyperactivity, aggression, self-abusive behaviour, temper tantrums, lability of mood and irritability. Adverse effects of antipsychotics include sedation, dizziness, increased appetite, weight gain, changes in the electrocardiogram parameters, drooling, hyperprolactinemia and a risk of drug-related dyskinesias.Other agents have been less well studied for the treatment of autism, but there are suggestive data regarding their safety and efficacy. Of these agents, a number have been investigated, based on theories about the aetiology of autism, including SSRIs and naltrexone, although the efficacy of these agents has been limited. Stimulant drugs have been shown to reduce hyperactivity and improve focus, but they may cause behavioural worsening, weight loss and stereotypies de novo. Secretin is a treatment that has received much media attention after reports of efficacy from small open studies, but all controlled studies have failed to show any benefit. In autism, alternative treatments have also been used, but none have shown benefit in well-designed studies.

Community service utilization by youths hospitalized in a state psychiatric facility

A majority of a cohort of 62 children and adolescents who had been hospitalized in a state psychiatric facility was found to have received less restrictive services such as outpatient mental health services prior to their index admission. Also, a number had been involved with the juvenile justice system and almost two-thirds had been placed out-of-home. Ninety percent had at least one prior psychiatric hospitalization. Just over half of the cohort received case management and individual counseling post release. About a third received family counseling, and a few received other types of services. At least a third were rehospitalized within a year of release. Although 90% of the cohort received some type of service post release, a higher proportion of non service receivers were rehospitalized than service receivers. Even those who received services had a high rate of rehospitalization. These findings raise questions as to the appropriateness of service provision during and following hospitalization.

Impersistence of depression in youth: Implications for drug study design.

Food and Drug Administration data show that most antidepressant studies in youth do not show drug effect. The few positive studies used rigorous diagnostic screening procedures, suggesting major depressive disorder (MDD) may not be a persistent condition in a subgroup of youth. To investigate persistence of MDD, we serially assessed a cohort of inpatients admitted to the hospital with a clinical diagnosis of MDD. Assessments included a structured diagnostic interview, the Diagnostic Interview for Children and Adolescents‐Revised (DICA‐R), and measures of depressive symptomatology. Of 66 subjects (40 girls; mean age, 14.4 ± 2.2 years), 34 (51.5%) met DICA‐R criteria for MDD at the initial postadmission assessment. Of these, only 8 (23.5%) met DICA‐R criteria for MDD at any subsequent assessment. Similar reductions were found on other ratings of depression. In conclusion, MDD did not persist in this sample. The findings suggest a multigated assessment procedure should be employed before randomization in antidepressant clinical trials.