$50 million PCORI funding approved for studies focused on treating suicidal depression and bipolar depression

Research teams at Mass General Brigham's founding members, Brigham and Women's Hospital (BWH) and Massachusetts General Hospital (MGH), have been approved for more than $50 million in funding awards by the Patient-Centered Outcomes Research Institute (PCORI) for studies focused on treating two important mental health conditions. Both projects are large-scale, high-impact research trials that will invite patients to participate at sites throughout the country, including at MGH, Brigham and Women's Faulkner Hospital (BWFH), and McLean Hospital, all members of the Mass General Brigham system.

Reversing acute suicidal depressed state

The research team at BWH, led by Amit Anand, MD, director of Translational Clinical Trials in the Department of Psychiatry, will receive more than $28.5 million in funding for work comparing the effectiveness of two treatments for acute suicidal depressed state (ASDS). Each year, 10 million Americans seriously consider suicide and 1.5 million attempt it. Among people 18 to 34 years old, suicide is now the second leading cause of death.

People with ASDS have an intent of imminent suicide or have attempted suicide. Once ASDS has set in, it requires rapid reversal with medical treatment such as electroconvulsive therapy (ECT) or subanesthetic intravenous ketamine (KET). But many patients receive inadequate treatment -; some are given antidepressants and discharged within 4-5 days of hospitalization. Anand and colleagues are proposing a real-world trial in ASDS patients to compare the effectiveness of ECT and KET to better inform patient care. Study participants will receive one of the two treatments as well as Collaborative Assessment and Management of Suicidality (CAMS) psychotherapy, which develops a therapeutic alliance with the patient to decrease suicidal thoughts. The study will include 1,500 participants with ASDS, enrolled from sites across the country, including BWFH. The research team will also build a stakeholder committee consisting of patients, their families, and representatives from patient advocacy organizations to provide suggestions for the study's design and monitor its implementation.

Suicide rates have risen alarmingly, and we urgently need to improve our understanding of how to treat and reverse ASDS. Our study will be the largest clinical trial ever conducted with ASDS patients and will provide invaluable data regarding how we can treat this life-threatening condition."

Amit Anand, MD, Director of Translational Clinical Trials, Department of Psychiatry

"This collaborative research aims to increase our understanding of effective interventions for optimal clinical outcomes that can decrease suffering and prevent suicides," said Bo Hu, Ph.D., of Cleveland Clinic's Lerner Research Institute and co-primary investigator on the grant. "By conducting a study at this large of a scale and using state-of-the-art data analysis methods, we will address critical knowledge gaps about treatment for ASDS."

Treating bipolar depression

The team at MGH, led by Andrew A. Nierenberg, MD, director of the Dauten Family Center for Bipolar Treatment Innovation, and Andrea Foulkes, PhD, director of Biostatistics, will use their nearly $25 million in funding to compare the effectiveness of four treatments for bipolar depression. Bipolar disorder is characterized by episodes of depression that include low mood and energy, and episodes of mania that are associated with elevated mood, high energy, and lack of sleep. During depressive episodes, people may experience an increase in suicidal thoughts, suicidal behavior, and death by suicide. To date, no studies have compared multiple approved treatment options for depression in bipolar disorder. The MGH team plans to evaluate the safety and effectiveness of four treatments: cariprazine, lurasidone, quetiapine and a commonly used, but unstudied, antipsychotic and antidepressant combination. They also plan to identify specific clinical features in patients that can help with choice of medication. The study aims to recruit 2,800 participants from sites across the country, including MGH and McLean Hospital. The research team will reach out and engage representative stakeholders (patients with bipolar depression, clinicians, insurance providers) and incorporate their input in all areas of study design, implementation, and dissemination of results.

"Comparative effectiveness studies are needed to address critical questions about how best to treat people with bipolar disorder who have major depressive episodes," said Foulkes. "Our goal is to provide robust, scientifically rigorous data to help clinicians and their patients make informed decisions about a treatment plan."

"The results of this study will help patients with bipolar depression who are seeking treatment, as well as the clinicians treating them, with deciding which medication to try first and what to choose next if the first option does not work or has unbearable side effects," said Nierenberg.

"These studies were selected for PCORI funding based on their scientific merit and commitment to engaging patients in conducting major research efforts on acute suicidal depression and bipolar depression," said PCORI Executive Director Nakela L. Cook, MD, MPH. "The studies have the potential to fill important evidence gaps relevant to a range of health care decision makers and help them better assess their care options. We look forward to following the studies' progress and working with the research teams to share their results."

Both studies were selected for funding through a PCORI initiative to support large-scale, high-impact comparative effectiveness research trials in a multi-phase format that allows for testing and refinement of the study approach. The studies will involve an initial feasibility phase to maximize the likelihood of full trial success. The studies were selected through a highly competitive review process in which patients, caregivers, and other stakeholders joined scientists to evaluate the proposals.

Both awards have been approved pending completion of business and programmatic reviews by PCORI staff and issuance of formal award contracts.