Michael T. Sorter

A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder.

OBJECTIVE To conduct a pilot study comparing the effects of quetiapine and placebo for the treatment of depressive episodes in adolescents with bipolar I disorder. METHOD Thirty-two adolescents (ages 12-18 years) with a depressive episode associated with bipolar I disorder were randomized to eight weeks of double-blind treatment with quetiapine, 300-600 mg/day, or placebo. This two-site study was conducted from March 2006 through August 2007. The primary efficacy measure was change in Childrens Depression Rating Scale-Revised Version (CDRS-R) scores from baseline to endpoint. Secondary efficacy measures included change in CDRS-R scores over the eight-week study period (PROC MIXED), changes from baseline to endpoint in Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS), and Clinical Global Impression-Bipolar Version Severity (CGI-BP-S) scores, as well as response and remission rates. Safety and tolerability were assessed weekly. RESULTS There was no statistically significant treatment group difference in change in CDRS-R scores from baseline to endpoint (p = 0.89, effect size =-0.05, 95% confidence interval: -0.77-0.68), nor in the average rate of change over the eight weeks of the study (p = 0.95). Additionally, there were no statistically significant differences in response (placebo =67% versus quetiapine = 71%) or remission (placebo = 40% versus quetiapine = 35%) rates, or change in HAM-A, YMRS, or CGI-BP-S scores (all p > 0.7) between treatment groups. Dizziness was more commonly reported in the quetiapine (41%) than in the placebo (7%) group (Fishers exact test, p = 0.04). CONCLUSIONS The results suggest that quetiapine monotherapy is no more effective than placebo for the treatment of depression in adolescents with bipolar disorder. However, limitations of the study, including the high placebo response rate, may have contributed to our findings and should be considered in the design of future investigations of pharmacological interventions for this population.

Olanzapine in the treatment of adolescent acute mania: a report of seven cases

BACKGROUND Clozapine may be effective in adults and adolescents with treatment-resistant bipolar disorder. Olanzapine has a receptor affinity profile similar to that of clozapine. METHODS The responses of seven consecutive adolescents (ages 12-17) with DSM-IV bipolar disorder, manic episode, treated with olanzapine were evaluated. Response to olanzapine was rated as marked, moderate, minimal, none or worse. RESULTS Five (71%) adolescents showed a marked or moderate response. The mean+/-SD olanzapine dose was 0.146+/-0.086 mg/kg/day (11+/-6 mg/day). CONCLUSION Olanzapine may have antimanic effects in some adolescents with acute mania. Controlled studies of olanzapine in adolescent bipolar disorder appear to be warranted.

Long-Term Safety, Tolerability, and Clinical Efficacy of Quetiapine in Adolescents: An Open-Label Extension Trial

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n = 7) or bipolar disorder with psychotic features (n = 3) were eligible for entry into this single-site, 88-week, open-label trial. Subjects had completed a pharmacokinetic study over 23 days, during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day) (McConville et al. 2000). In the open-label extension of this trial, which followed directly after this trial, a physicians choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient, with ending doses ranging from 300 mg/day to 800 mg/day. Concomitant medications, especially for anxiety and/or manic symptoms, were allowed as deemed necessary. Tolerability and safety were assessed using clinical laboratory tests, physical examinations, measurements of vital signs, interviews for selective symptomatology, and electrocardiograms. Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and the modified Scale for the Assessment of Negative Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase in mean weight and body mass index at week 64. This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents.

Personality disorders in first- and multiple-episode mania

We compared rates of DSM-III-R personality disorders in 33 first-episode and 26 multiple-episode bipolar patients. Patients were evaluated with the patient and personality disorders versions of the Structured Clinical Interview for DSM-III-R. Significantly more multiple-episode patients (65%) met DSM-III-R criteria for a personality disorder than did first-episode patients (33%). Race was also associated with a diagnosis of a personality disorder. Personality disorders may be associated with multiple affective episodes in bipolar patients.

Antipsychotic polypharmacy in children and adolescents at discharge from psychiatric hospitalization.

Antipsychotic polypharmacy―the use of more than one antipsychotic concomitantly—has increased in children and adolescents and may be associated with increased adverse effects, nonadherence, and greater costs. Thus, we sought to examine the demographic and clinical characteristics of psychiatrically hospitalized children and adolescents who were prescribed antipsychotic polypharmacy and to identify predictors of this prescribing pattern.

Effectiveness of the Surviving the Teens® Suicide Prevention and Depression Awareness Program An Impact Evaluation Utilizing a Comparison Group

Youth suicide is a serious public health issue in the United States. It is currently the third leading cause of death for youth aged 10 to 19. School-based prevention programs may be an effective method of educating youth and enhancing their help-seeking. Most school-based suicide prevention programs have not been rigorously evaluated for their effectiveness. This evaluation employs a comparison group to measure whether program group participants differed significantly from comparison group participants on pretest–posttest measures while assessing the immediate impact of the Surviving the Teens® Suicide Prevention and Depression Awareness Program. Findings indicate several positive outcomes in program group students’ suicide and depression knowledge, attitudes, confidence, and behavioral intentions compared with the comparison group. Suicide prevention specialists and prevention planners may benefit from study findings.

Physician Leadership and Quality Improvement in the Acute Child and Adolescent Psychiatric Care Setting

Inpatient child and adolescent psychiatry leadership roles are often multifaceted, necessitating strong clinical knowledge and skills, organizational and leadership abilities, and in the academic setting the desire and skill in teaching and research. Early career psychiatrists who do possess these attributes may find themselves unprepared for such challenges as dealing with complex administrative and economic issues, accreditation, legal matters, and multitasking. This article offers a primer addressing these basic issues and in managing change through quality improvement processes.

Emotionally Troubled Teens' Help-Seeking Behaviors: An Evaluation of Surviving the Teens® Suicide Prevention and Depression Awareness Program.

Many school-based suicide prevention programs do not show a positive impact on help-seeking behaviors among emotionally troubled teens despite their being at high risk for suicide. This study is a secondary analysis of the Surviving the Teens® program evaluation to determine its effect on help-seeking behaviors among troubled youth. Results showed significant increases in mean scores of the Behavioral Intent to Communicate with Important Others Regarding Emotional Health Issues subscale (p < .0005) from pretest to 3-month follow-up. There was a significant increase (p = .006) in mean scores of the Behavioral Intent Regarding Help-Seeking Behaviors when Suicidal subscale from pretest to posttest, but not at 3-month follow-up. Also, there was a significant increase (p = .016) in mean scores in the item “I would tell an adult if I was suicidal” from pretest to 3-month follow-up. These findings suggest that the Surviving the Teens program has a positive effect on help-seeking behaviors in troubled youth.

Automated Risk Assessment for School Violence: a Pilot Study

School violence has increased over the past ten years. This study evaluated students using a more standard and sensitive method to help identify students who are at high risk for school violence. 103 participants were recruited through Cincinnati Children’s Hospital Medical Center (CCHMC) from psychiatry outpatient clinics, the inpatient units, and the emergency department. Participants (ages 12–18) were active students in 74 traditional schools (i.e. non-online education). Collateral information was gathered from guardians before participants were evaluated. School risk evaluations were performed with each participant, and audio recordings from the evaluations were later transcribed and manually annotated. The BRACHA (School Version) and the School Safety Scale (SSS), both 14-item scales, were used. A template of open-ended questions was also used. This analysis included 103 participants who were recruited from 74 different schools. Of the 103 students evaluated, 55 were found to be moderate to high risk and 48 were found to be low risk based on the paper risk assessments including the BRACHA and SSS. Both the BRACHA and the SSS were highly correlated with risk of violence to others (Pearson correlations>0.82). There were significant differences in BRACHA and SSS total scores between low risk and high risk to others groups (p-values <0.001 under unpaired t-test). In particular, there were significant differences in individual SSS items between the two groups (p-value <0.001). Of these items, Previous Violent Behavior (Pearson Correlation = 0.80), Impulsivity (0.69), School Problems (0.64), and Negative Attitudes (0.61) were positively correlated with risk to others. The novel machine learning algorithm achieved an AUC of 91.02% when using the interview content to predict risk of school violence, and the AUC increased to 91.45% when demographic and socioeconomic data were added. Our study indicates that the BRACHA and SSS are clinically useful for assessing risk for school violence. The machine learning algorithm was highly accurate in assessing school violence risk.

Implementation of Pharmacogenetics at Cincinnati Children's Hospital Medical Center: Lessons Learned Over 14 Years of Personalizing Medicine

Significant inter-individual variability in medication response can result in adverse drug reactions (ADRs) and increased health care costs. Based on ADR prevalence and mounting evidence linking genetics and pharmacokinetic variability, Cincinnati Children’s Hospital Medical Center (CCHMC) launched the Genetic Pharmacology Service (GPS) in 2004 and has since performed >25,000 tests. Herein, we describe how the service developed, launched, and has been updated along with how it is currently utilized, and key lessons learned.