Source: Haematologica  |  Posted 6 years ago

Paula Moyer

TORONTO, CANADA -- October 31, 2005 -- Aripiprazole (Abilify) is effective for treatment of bipolar disorder as well as schizophrenia in children and adolescents, who tolerate the drug well across several doses, according to research presented here at a joint meeting of the American and Canadian Academies of Child and Adolescent Psychiatry (AACAP/CACAP).

Aripiprazole has been approved to treat these disorders in adults but has not yet been approved for use in the pediatric setting, according to principal investigator Robert L. Findling, MD, Professor of Psychiatry and Pediatrics, Case Western Reserve University, and Director of Child and Adolescent Psychiatry, University Hospitals of Cleveland, Cleveland, Ohio, United States,.

"This study provides support for the exploration of the entire adult dose range of aripiprazole in schizophrenia and bipolar disorder," Dr. Findling said, noting that investigators are currently conducting clinical trials on aripiprazole in children and adolescents with such diagnoses.

Using aripiprazole to treat severe mental illnesses in children and adolescents constitutes the latest development in the search for a more benign antipsychotic agent. Atypical antipsychotics, such as aripiprazole, do not cause the extrapyramidal symptoms (EPS) that are the hallmark of conventional antipsychotics, but the newer drugs are often associated with weight gain and lipid dysregulation.

Aripiprazole apparently is not linked to metabolic adverse effects; although these were not the focus of the current research. Therefore, Dr. Findling and his co-investigators wanted to see whether aripiprazole would be an appropriate treatment option in children with such severe conditions.

The Food and Drug Administration (FDA) requested that the investigators study the tolerability of aripiprazole in children and adolescents at three doses. Therefore, Dr. Findling and co-investigators recruited 19 patients with schizophrenia, schizenophreniform, and bipolar disorder, who were 10 to 17 years old.

The researchers studied subjects' ability to tolerate aripiprazole at doses often used to treat adults. Patients were started at doses of 2 mg daily and then received daily doses that increased first to 5 mg daily and increased in increments of 5 mg until they reached one of the following dose levels: 20 mg, 25 mg, or 30 mg. Patients continued to take the medication at the target doses for an additional 14 days.

Among these patients, 89% were either "improved" or "much improved," according to physicians who assessed them with the Clinical Global Impression (CGI) Improvement score. The baseline average CGI-Severity score was 3.7(moderately ill); the score at the end of the study was 1.9 (borderline ill).

The investigators assessed the medication's safety with the spontaneous reporting of adverse events, electrocardiography, vital signs, clinical laboratory tests, a physical exam, and the ExtraPyramidal Symptoms rating sales, including the Simpson-Angus scale, the Abnormal Involuntary Movement scale, and the Barnes Akathisia Rating Scale.

During the study, four patients discontinued treatment, one due to dystonia, one due to a protocol violation, and two due to parental withdrawal of consent.

The most common adverse events were blurred vision, excessive sleepiness or its opposite, insomnia, and headache. Adverse events were typically transient and occurred at equivalent rates across the three target doses.

The investigators concluded that aripiprazole was well tolerated in female and male children and adolescents, regardless of their psychiatric diagnoses, Dr. Findling said.

The study was funded by Otsuka Pharmaceuticals, which manufactures Abilify in partnership with Bristol Myers Squibb.

[Presentation title: Tolerability of Aripiprazole in Children and Adolescents with Major Psychiatric Diagnoses. Abstract C-5]