The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.
Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.
A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.
The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.
Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).
The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.
In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.
A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.
Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.