Joseph Blader PhD Offers Advice for Improving Drug Studies


In a letter to the editor of the Journal of the American Academy of Child and Adolescent Psychiatry, Joseph Blader, PhD commented on a series of articles examining the relative effectiveness of drugs used to treat mania in young people with bipolar disorder.

A previously published article by Barbara Geller, MD and colleagues reported the results of a multi-site trial showing that risperidone is more effective than lithium or divalproex for the initial acute treatment of mania in children and adolescents with bipolar I disorder. A secondary analysis by Benedetto Vitiello, MD examining potential influences on outcomes in addition to the medications found that treatment site and the severity of ADHD symptoms had significant effects on treatment outcomes.

In his letter, Dr. Blader discussed implications of the trial’s results for improving future studies. First, because the secondary analyses showed large differences between study sites, he argued that location should be included as a random effect in primary efficacy analyses when studies are conducted at multiple sites. While recognizing that trials that account for variation among sites can be more expensive and take longer, Dr. Blader called attention to the even greater costs associated with imprecise or misleading estimates of treatment effects. Second, because the severity of comorbid ADHD symptoms predicted generally worse outcomes, he pointed out the value of first optimizing first-line therapies for ADHD, when tolerated, before progressing to evaluate drugs used for the treatment of bipolar disorder in young people with ADHD.  In the original study, even though 93% of the participants were diagnosed with co-morbid ADHD and most continued their pre-trial ADHD stimulant treatment during the study, no attempt was made to ensure that stimulant therapy was adequate.  Third, he noted the need for researchers to provide a more comprehensive profile of their trial participants so that clinicians can form a clearer idea of which patients the research might apply to.  One important factor to reconcile, he wrote, was the unusually high prevalence of psychotic features (nearly 80% of the study’s patients) while the investigator permitted many of them to continue use of stimulant medications, which ordinarily worsen or even elicit psychotic symptoms.