Lead Investigator: Frederick Reimherr, Psychiatric and Behavioral Solutions, LLC
Title of Proposal Research: Retrospective Analysis of Emotional Symptoms in Adults with ADHD and Improvement Produced by Brexpiprazole
Vivli Data Request: 7241
Funding Source: None
Potential Conflicts of Interest: As a primary investigator, Frederick W. Reimherr has received research funding from Otsuka. PBSolutions was one of the sites for the Otsuka 213 trial. He has also received research funding from others including: Eli Lilly, GSK, Shire and McNeil.
At this time we are not participating in ADHD trials with Otsuka or other companies. At present, there are no medications that have an FDA approval for treatment-resistant ADHD. In fact, there are literally no published reports on how to deal with this problem in adults with ADHD. Finally, brexpiprazole was not tested as a stand-alone medication. The study used brexpiprazole as an “add-on” medication to enhance the effect of standard ADHD medications. So it would not compete with any available ADHD medication.
Summary of the Proposed Research:
Protocol # 331-08-213 represents a remarkable effort by a pharmaceutical company. Both in academic and industry research, there have been very few studies targeting treatment resistant adult ADHD (Attention Deficit Hyperactivity Disorder).
Much research describes the importance of emotional symptoms in ADHD. In child psychiatry, ADHD’s emotional symptoms are frequently resistant to treatment.
The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) assesses seven symptom domains. We have shown that the scale has two factors. These domains and factors allow us to define two types of ADHD: ADHD Inattentive presentation and ADHD Emotional dysregulation presentation. More psychopathology and dysfunction are associated with the latter. Both respond to treatment.
Fortunately this scale was included as a secondary outcome measure, in this trial. Preliminary analysis of Protocol # 331-08-213 using the ADHD-Rating Scale (ADHD-RS) produced results that did not show efficacy, but results using the WRAADDS were more encouraging.
We would like to reanalyze the data in three stages.
1) What are the remaining symptoms after treatment representing manifestations of poor outcome in treatment resistant ADHD?
2) Does in fact the WRAADDS show that brexpiprazole demonstrated significant efficacy in treatment resistant ADHD?
3) We have published psychometric data showing that this scale contains an attentional and an emotional factor. We would like to examine whether brexpiprazole effects both these factors.
4) We have also published an intital paper and a replication showing that adults with ADHD can be divided into 2 types: ADHD inattentive presentation and ADHD Emotional dysregulation presentation. We would assess wether brexpiprazole shows similar efficacy in both presentations.
In addition data from this trial would allow us to contrast the two ADHD types on secondary measures (Adult ADHD Quality of Life measure (AAQoL), Quality of Life Enjoyment and Satisfaction Questionnaire—Short Form (LES-QSF), Montgomery-Asberg Depression Rating Scale (MADRS) and Beck depression rating scale).
Statistical Analysis Plan:
Assessment of residual, treatment-resistant, baseline symptoms (end of Phase A) will be analyzed using descriptive statistics; and by contrasting groups using analysis of variance (ANOVA) for continuous variables and nonparametric statistics for categorical variables.
Treatment efficacy of brexpiprazole during Phase B will be analyzed using repeated-measures, mixed models ANOVA. Subjects will be intent-to-treat including all subjects who take at least one dose of brexpiprazole, have baseline data and at least one post-baseling outcome score. The total Wender Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and both of its factors will be used as outcome measures for these 3 analyses.
Subjects will be categorized into 2 Attention Deficit Hyperactive Disorder (ADHD) presentations using previously published procedures. The relative treatment response for the 2 groups will be compared using repeated-measures, mixed models ANOVA. Differences between the 2 groups will be analyzed using ANOVA or non-parametric tests as appropriate.
Differences between these 2 groups regarding the secondary measures (i.e. Adult ADHD Quality of Life (AAQoL), Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (LES-QSF), etc) will be analyzed using descriptive statistics as well as ANOVA controlling for multi-measures. (A Bonferroni correction will be applied as appropriate.)
A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Adult Attention Deficit/ Hyperactivity Disorder
Data Contributor: Otsuka Pharmaceuticals
Study ID: NCT01074294
Sponsor ID: 331-08-213
Reimherr, Frederick W.; Gift, Thomas E.; Steans, Tammy A.; Reimherr, Matthew L.; Rosenberg, Leon I.; Wilson, Melissa; Marchant, Barrie K. The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder. Journal of Clinical Psychopharmacology: August 17, 2022 – Volume – Issue – 10.1097/JCP.0000000000001592. doi: 10.1097/JCP.0000000000001592.