CINCINNATI, OH—When Cindy Starr’s daughter was diagnosed with bipolar disorder at age 18, the Starr family began a difficult journey. Over the next two years, doctors prescribed a series of second-generation antipsychotics (SGAs). The medicines helped with some of the symptoms but didn’t completely stabilize mood. The medicines also had considerable side effects, including lethargy and weight gain. Starr’s daughter gained 20 pounds.
“I was very concerned about my daughter’s health and her weight gain during that time,” says Starr, a writer and media relations specialist at the University of Cincinnati. Finally, however, a doctor prescribed an older medication, lithium, instead of an SGA. That change helped Starr’s daughter stabilize her bipolar symptoms and her weight. Her nutritional habits also improved: she became a vegetarian and eventually lost all the weight she had gained.
SGAs are first-line treatments for bipolar disorder in childhood and adolescence because recent studies have shown these medicines to be particularly effective in that group. Lithium is, in general, less effective and can have its own serious side effects, but it leads to less weight gain than SGAs. The greater weight gain that often results from SGAs can pose its own serious risks of obesity, as well as high cholesterol and insulin resistance that may lead to metabolic syndrome and diabetes. The weight gain can negatively affect youths’ willingness to take medication, quality of life, and overall satisfaction with their health care.
“Weight gain from SGAs is the top-rated side effect of concern among patients, families, and clinicians,” says Melissa P. DelBello, MD, MS, professor of psychiatry and pediatrics at the University of Cincinnati College of Medicine. “We want to give patients treatment options to prevent or manage weight gain, and prevent the progression of obesity to insulin resistance and diabetes.”
Weight gain from SGAs is the top-rated side effect of concern among patients, families, and clinicians.
To test a strategy to prevent weight gain related to SGAs, DelBello is leading a large PCORI-funded study. DelBello, co-investigator Christoph Correll, MD, of the Feinstein Institute for Medical Research in Manhassett, New York, and other researchers have teamed with healthcare stakeholders, including Starr, patient advocates, and clinicians. They will counsel all participants and their families on healthy eating and physical activity. For half the participants, clinicians will prescribe metformin, a drug that helps people with type 2 diabetes control the amount of sugar in their blood.
The research team is recruiting 1,800 overweight or obese youth, ages 8 to 19, who are undergoing treatment with SGAs for bipolar disorder at 40 community mental health clinics in the greater Ohio and New York regions. The study is part of PCORI’s pragmatic research initiative, which funds large-scale comparative clinical effectiveness research studies that measure the benefits and harms of two or more healthcare options in real-world settings.
Studying Weight Loss and Patient Quality of Life
Metformin may prevent or reduce the amount of weight gain that can occur in young people taking SGAs, some studies have indicated, but this off-label use is not common or widespread. DelBello notes that many of the earlier studies were conducted in academic settings and didn’t focus on patient-centered outcomes, such as health-related quality of life.
So she decided to do a large study, called the MOBILITY trial, which takes place predominantly in community mental health facilities. “We hope to find out if a combination of metformin and lifestyle interventions can be easily effective when used in a real-world clinical setting,” she says.
The study’s lifestyle interventions consist of videos on the study’s website that provide basic information about maintaining healthy eating and physical activity habits. The site also provides information about an eating and exercise plan and refers parents and patients to other sources of information about weight control.
The videos help patients and parents follow a meal plan designed for optimal weight loss and management. The plan categorizes foods into red-light, yellow-light, and green-light categories. Participants are directed to eat red-light foods sparingly, yellow-light foods in moderation, and green-light foods as often as they like.
“This approach makes the process of nutritional change very easy to understand,” says Angie Day, chapter and volunteer services director for the Depression and Bipolar Support Alliance (DBSA) and manager of DBSA’s Balanced Mind Parent Network, an online community of parents who have children living with bipolar disorder.
The healthy lifestyle plan also encourages exercise. The initial goal is at least one hour of physical activity daily, and then, if appropriate, participants can gradually increase activity to two hours daily.
The researchers plan to follow each participant for two years, assessing weight gain and measures of metabolic health, such as cholesterol and glucose levels in the blood. They will also consider mood, anxiety levels, overall functioning in school and relationships, and other patient-centered outcomes. DelBello says, “As part of our quality-of-life assessments, we’ll also be looking at medication adherence and patient and family attitudes toward medication.”
The research team will collect clinical information from patient records. In addition, patients and their caregivers will fill out questionnaires about the patients’ quality of life monthly for the first three months after enrollment in the study, and then every three months. At every clinic visit, the research team will check for physical or behavioral problems that might be related to the treatment.
The MOBILITY study is crucial because we want adolescents to have the best health possible, while also feeling good about themselves.
Designed by the Healthcare Community
Even before the research began, the researchers asked for the opinions of mental health advocates and other stakeholders. In an online survey administered through the DBSA and the National Alliance on Mental Illness, 497 patients, 344 caregivers, and 54 clinicians provided opinions on the most important questions for the study to consider.
Members of DBSA’s Balanced Mind Parent Network provided insight and feedback during the design of the MOBILITY study. Clinicians and patient advocates also contributed ideas about the proposed measures and design.
“The families, clinicians, and mental health advocates reviewed and offered insight on all aspects of the study,” says Jenna Nott, MOBILITY project director. “They suggested changes that improved the design of the study, such as using more understandable language in the questionnaires and educational materials.”
Patients at the Center
“For DBSA, having the patient perspective at the center of the conversation about the MOBILITY study will make the results more meaningful,” says Day. The study’s research team includes scientific experts, patients and parents, advocacy and professional organization leaders, clinicians, and public and private insurers. They are serving as co-investigators and advisors, as well as committee members and chairs of the project’s eight committees that oversee its implementation.
Communication within the study is key, DelBello says. The project has two newsletters; one goes to the 40 clinical sites, the other to committee members. Via the study’s Twitter account, participants are sharing tips about lifestyle tactics they find useful. Stakeholder committee members oversee the content of the tweets.
The research team intends to rapidly disseminate its findings, expected in about three years, to reduce uncertainty about prescribing metformin to manage weight in young people treated with SGAs for bipolar disorder. DelBello says the results may also be relevant to adults who take SGAs for bipolar disorder and to people with autism or psychotic symptoms who rely on those drugs.
Starr, the mother whose daughter had gained weight, looks forward to the results. “If the MOBILITY study can discover whether metformin keeps patients from gaining weight while on medications for bipolar disorder, then the results will help families and patients avoid adding that additional challenge to their lives,” she says.
Day adds, “The MOBILITY study is crucial because we want adolescents to have the best health possible, while also feeling good about themselves.”
Mobility: Improving Patient-Centered Outcomes Among Overweight and Obese Youth with Bipolar Spectrum Disorders Treated with Second-Generation Antipsychotics
Principal Investigator: Melissa P. DelBello, MD, MS
Goal: Assess whether the medication metformin, combined with diet and exercise, is more effective than lifestyle changes alone to prevent or reverse weight gain in children and teenagers with bipolar disorder treated with second-generation antipsychotics.
PCORI Research Topic: Obesity
Posted: April 11, 2017