Interim results will soon be analyzed in a longitudinal study examining biological and genetic risk factors for weight gain and metabolic abnormalities in children and adolescents taking atypical antipsychotics, principal investigator Christoph Correll, M.D., told Psychiatric Times. Correll is a physician in the division of child and adolescent psychiatry of Schneider Children's Hospital and Zucker Hillside Hospital in Glen Oaks, N.Y.
The open-label, naturalistic safety monitoring study, underway since December 2001, is being funded by the National Institute of Mental Health and the National Alliance for Research on Schizophrenia and Depression (NARSAD). Grants have also been awarded to the co-principal investigator, Anil Malhotra, M.D., acting director of the department of psychiatry research, Zucker Hillside Hospital and Long Island Jewish Medical Center in New York. The study involves children and adolescents ages 5 to 18 who have a clinical diagnosis of a psychotic disorder (e.g., schizophrenia or schizoaffective disorder), mood disorder (e.g., bipolar disorder or major depressive disorder) or aggressive disorder (e.g., oppositional defiant disorder, conduct disorder or intermittent explosive disorder). Of the 301 youngsters who met study inclusion criteria, 242 (80.4%) have consented to participate over the past 28 months, which equates to a mean enrollment rate of 2.2 youngsters per week.
The mean age of the study participants is 13.7 years, with 66.5% being postpubertal. More than half (57.9%) of the participants are male; 45% are white; 26%, African-American; 12%, Hispanic; 3.7%, Asian; and 13.6%, mixed ethnic origin.
When clinical diagnosis is considered, 43.4% of the patients have mood disorders; 28.9%, schizophrenia spectrum disorders; and 27.9%, aggressive/disruptive behavior spectrum disorders. More than half (58.2%) of the patients are considered antipsychotic-naive (i.e., less than one week of lifetime antipsychotic exposure); 19% have a history of antipsychotic treatment but are antipsychotic-free after taking the drugs for at least four weeks; and 22.7% are switching from one atypical antipsychotic to another due to side effects or lack of efficacy. The researchers also are following patients who have restarted an atypical antipsychotic after a period of nonadherence or when they are switched from the initial index antipsychotic. This increases their total number of trials and allows them to study order effects of treatment.
Study participants are monitored once they begin using one of the six atypical antipsychotics currently on the U.S. market. So far, there have been 104 trials of risperidone(Drug information on risperidone) (Risperdal); 72 of olanzapine (Zyprexa); 68 of quetiapine (Seroquel); 38 of aripiprazole(Drug information on aripiprazole) (Abilify); 17 of ziprasidone(Drug information on ziprasidone) (Geodon); and five of clozapine(Drug information on clozapine) (Clozaril).
The acute phase of the study lasts three months, during which patients are seen monthly. Those patients who continue on the index antipsychotic medication are enrolled in the extension phase and followed every three months thereafter. Initially, researchers obtain a DNA sample from the patient and then collect information on the patient's personal and family history of metabolic syndrome and history of noncompliance.
The baseline and monthly monitoring includes measurements of height, weight, body mass index (BMI), total fat mass and percentage (via bio-impedance measurement), and hip-waist ratio, as well as Weight Attitude, treatment-emergent side effects, Simpson-Angus Scale (SAS) for extrapyramidal symptoms, Abnormal Involuntary Movement Scale (AIMS) for tardive dyskinesia, Clinical Global Impressions Scale (CGI), Children's Global Assessment Scale (CGAS), Drug Attitude Inventory, Life Satisfaction and Compliance Interview.