Melissa P DelBello, MD, MS Department of Psychiatry & Behavioral Neuroscience University of Cincinnati College of Medicine
Timeline • January 2014 Dr. Hutton introduces us to PCORI & AHRQ report • February 2014 Stakeholders engaged • March 2014 LOI submitted • June 2014 LOI resubmitted • July 2014 Invited for full proposal • August 2014 New York (LIJ) on board • November 2014 Submitted full proposal • Winter 2014-2015 Reviewed • April 2015 PCORI Board of Directors recommends us for funding • October 2015 Kick-off
Background • Second Generation Antipsychotics (SGAs) are the most effective treatments for youth with bipolar spectrum disorders (BSD). • The short- and long-term use of SGAs in youth are among the top research priorities of the Agency for Healthcare Research & Quality (AHRQ). – PCORI cites AHRQ priorities as a major determinant of its own evaluation of the potential of proposed studies . • SGAs are often associated with significant weight gain and metabolic concerns, especially in youth . – 70% of youth taking SGAs are overweight or obese . • Rigorously conducted studies demonstrate that metformin is effective for mitigating weight gain in youth. Correll, Sheridan, DelBello, Bipolar Disord , 2010; Geller B Arch Gen Psychiatry, 2012; Pavuluri et al., Bipolar Disord , 2010; DelBello et al., JAACAP , 2006
• Why then in standard clinical practice are few patients with bipolar spectrum disorders prescribed metformin for the metabolic side effects associated with SGAs?
Patient Engagement Pilot Survey • Need preliminary data to ensure importance to patients, parents and clinicians. • Depression and Bipolar Support Alliance (DBSA) has a well-established online parent support network. • Concern regarding bias to those without computer so regional National Alliance on Mental Illness (NAMI) engaged.
Patient, Parent & Clinician Surveys • Survey monkey for patients, parents and clinicians. • DBSA online parent group & NAMI • Sent to regional American Academy of Child and Adolescent Psychiatry listserv • 2 weeks • > 900 responders • Brief Questionnaire • Patient (9 items) • Parent (7 items) • Clinician (10 items)
Key Survey Results • Patients (n=186 diagnosed with Bipolar Disorder < age 18). • 37% took meds less than 75% of the time as prescribed. • Weight gain was the most concerning side effect by 46% • Weight gain was the most common reason for non-adherence (65%). • Also common were forgetting (60%) sedation (60%) and “didn’t like being told what to do” (45%). • 90% willing to concomitantly start a second medication to mitigate potential weight gain. • Parents (n=310) • Weight gain was the most concerning side effect by 40% • 85% would start medication, but lifestyle was most acceptable intervention.
More Preliminary Data • Clinicians (n=54) • Thirty-seven (69.8%) clinicians responded that they were not at all likely to prescribe metformin at the same time as initiating SGA therapy in otherwise stable patients. • 45 (86.5%) responded that they would be somewhat or extremely likely to add metformin if the patient were to complain about weight gain. • 74% had prescribed metformin • Most common reason for not prescribing is unsure how. • Humana Database • Over an ~3 year period, only 1.7% of 2650 youth ages 8-17 who treated with an SGA were also prescribed metformin.
A PCORI Supported Pragmatic Trial Melissa DelBello MD-U of Cincinnati Christoph U. Correll MD-Hofstra/Northwell (NSLIJ) Principal investigators LIFESTYLE BMI >85%ile Bipolar spectrum disorder Structured diet/exercise Bipolar I, II, NOS, Any SGA Mood disorder NOS + LIFESTYLE Ages 8-17 Disruptive Mood Dysreg. d/o Structured diet/exercise + Total N: 1800 METFORMIN Primary endpoints: 6 & 24 months Primary outcome: Change in Body Mass Index
Study Infrastructure
Outcome Domains Treatment BMI SGA (SGA) Z-score Adherence Satisfaction Insulin Glucose Weight & HgbA 1c Mood Metabolic & Health Lipid Profile Anxiety Diet & Satiety Quality of Life Weight Related QOL
Outcome Domains Depression Anxiety Treatment SGA (SGA) Anger Adherence Satisfaction Young Mania Rating Scale Children’s Depression Weight & Rating Scale Mood Metabolic Clinical Global & Health Improvement Anxiety Diet & Satiety Quality of Life Weight Related QOL
Specific Outcome Measures Treatment SGA (SGA) Adherence Satisfaction Weight & Mood Metabolic & Health Anxiety Global Health Diet & Peer Relationships Satiety Satisfaction with Weight Physical Function Caregiver Strain (Sizing Up) Social Avoidance School/Work Quality of Life Days Missed (Sizing Up) Positive Social Attributes Weight Clinical Global (Sizing Up) Assessment Scale Related Teasing / Marginalization QOL (Sizing Up) Bodyweight, Image, Self-esteem (B-WISE)
Outcome Domains Treatment SGA (SGA) Adherence Satisfaction Weight & Mood Metabolic & Health Anxiety Diet & Satiety Food Choices Eating Habits Quality of Life Cognitive Restraint Satiety Weight Responsiveness Related QOL
Outcomes Treatment (SGA) Antipsychotic Satisfaction (SGA) Adherence Weight & Metabolic Mood Health & Anxiety Metformin Diet & Satiety Quality of Life Additional outcomes identified as important by patients are Weight hypothesized to be indirectly improved with metformin Related treatment. QOL Most meet the needs and expectations of patients, but this requires a trade-off to avoid excessive burden.
Stakeholder Engagement • Study Design – No cluster randomization – LIFE feedback and video design – Broadening diagnostic inclusion criteria – Website development • Committee Leadership – Meeting times after school • Ongoing Feedback – Survey Development & Implementation – Committee and site questionnaire – Other stakeholder feedback
Stakeholders • Patient/Parent representatives • Scientific investigators (coordinating site, UC/LIJ) • Advocacy organizations (e.g. DBSA, NAMI) • Professional organizations (e.g. AACAP, Pediatric Endocrine Society) • Payers (e.g. Humana, Medicaid) • Health systems (e.g. North Shore/Long Island Jewish & UC Health) • Other (e.g. Rutger’s Center for Education and Research on Therapeutics)
Acknowledgements www.mobilitystudy.org • PCORI • Patients and their families • Family Advisory Committee • Depression and Bipolar Support Alliance • National Alliance on Mental Illness • Humana, Inc. • American Academy of Child & Adolescent Psychiatry • Christoph Correll, Jeff Welge, Thomas Bloom, Adam Carle, Nancy Crimmins, Angie Day, Ingrid Deetz, Victor Fornari, Claudine Higdon, Christy Klein, Avani Modi, Nick Patel, Rodrigo Patino, Eva Sheridan, Shawna Smith, Michael Sorter, Cindy Starr, Heather Turner • CCHMC IRB • University of Cincinnati & Long Island Jewish
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