Melissa P DelBello, MD, MS Department of Psychiatry & Behavioral - - PowerPoint PPT Presentation

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

• f 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

Bipolar spectrum disorder Bipolar I, II, NOS, Mood disorder NOS Disruptive Mood Dysreg. d/o BMI >85%ile Any SGA

+

LIFESTYLE Structured diet/exercise LIFESTYLE Structured diet/exercise + METFORMIN Ages 8-17 Total N: 1800 Primary endpoints: 6 & 24 months Primary outcome: Change in Body Mass Index

Study Infrastructure

SGA Adherence Mood & Anxiety

Quality of Life

Treatment (SGA) Satisfaction Weight & Metabolic Health

Outcome Domains

Weight Related QOL

Diet & Satiety

Insulin BMI Z-score Glucose HgbA1c Lipid Profile

SGA Adherence Mood & Anxiety

Quality of Life

Treatment (SGA) Satisfaction Weight & Metabolic Health

Outcome Domains

Weight Related QOL

Diet & Satiety

Depression Anxiety Anger Clinical Global Improvement Young Mania Rating Scale Children’s Depression Rating Scale

SGA Adherence Mood & Anxiety

Quality of Life

Physical Function (Sizing Up) Social Avoidance (Sizing Up) Positive Social Attributes (Sizing Up) Teasing / Marginalization (Sizing Up) Global Health Peer Relationships

Treatment (SGA) Satisfaction

Weight Related QOL

Weight & Metabolic Health

School/Work Days Missed Satisfaction with Weight Caregiver Strain Bodyweight, Image, Self-esteem (B-WISE) Clinical Global Assessment Scale

Specific Outcome Measures

Diet & Satiety

SGA Adherence Mood & Anxiety

Quality of Life

Treatment (SGA) Satisfaction Weight & Metabolic Health

Outcome Domains

Weight Related QOL

Diet & Satiety

Food Choices Cognitive Restraint Eating Habits Satiety Responsiveness

Antipsychotic (SGA) Adherence Mood & Anxiety

Quality of Life

Treatment (SGA) Satisfaction

Weight Related QOL

Weight & Metabolic Health

Additional outcomes identified as important by patients are hypothesized to be indirectly improved with metformin treatment. Most meet the needs and expectations of patients, but this requires a trade-off to avoid excessive burden.

Metformin Diet & Satiety

Outcomes

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

• 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

www.mobilitystudy.org