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.