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March 14, 2022

RE: Local health researcher’s study reveals that a drug used to treat type 2 diabetes can also successfully treat people living with treatment resistant bipolar disorder depression.

Halifax, NS: In recognition of Brain Awareness Week 2022—March 14 to 20—Dalhousie Medical Research Foundation (DMRF) is proud to announce that local health researcher, Dr. Cindy Calkin, recently published the results of a quadruple-masked randomized placebo-controlled trial (the TRIO-BD study) in the Journal of Clinical Psychiatry. This study revealed that metformin—a type 2 diabetes treatment drug—can successfully treat patients living with treatment resistant bipolar depression, by reversing insulin resistance, a pre-diabetic state that is associated with poor outcomes. 

Dr Calkin, who is an Associate Professor of Psychiatry and Medical Neuroscience and head of the Mood and Metabolism Program at Dalhousie University, says the discovery would vastly improve the lives of those living with significant treatment resistant bipolar disorder. Bipolar disorder is a severe mental health condition marked by extreme shifts in moods that can have devastating impacts on the person living with the disorder and their loved ones. This TRIO-BD-study—a gold standard clinical trial—is the first to look at treating an underlying mechanism of bipolar illness. 

“The majority of the patients in our study had been very sick with bipolar disorder for more than 25 years, without any relief of their symptoms,” explains Dr. Calkin. “These patients had not responded to 8 or 9 different medication trials from at least three of four different classes of mood stabilizers. They also had moderate anxiety and were severely impaired in their functioning. As you can imagine, this was an extremely difficult way to live.” 

The trial was supported by a $1.3 million grant from the Stanley Medical Research Institute in Rockville, Maryland. What Dr. Calkin and her team found was that those patients who became insulin sensitive with the metformin treatment had significant improvement in their depression, anxiety, and functioning. Continued follow-up to 26 weeks showed that these improvements are sustained at least in the intermediate term. 

“The patients are telling me that the quality of remission is different than with any other medication they have taken, “says Dr. Calkin. “They’ve said that this is as well as they have felt prior to developing bipolar disorder. Perhaps this is because we are treating the underlying mechanisms. The results of this study are very exciting.”

Dr Calkin and her team have since discovered—thanks to funding from a NARSAD award from the Brain and Behavior Research Foundation in New York, New York—that extensive leakage of the blood-brain barrier (BBB, meant to protect the brain from harmful molecules in the body’s blood stream) was found in patients with bipolar disorder, insulin resistance, and poor outcomes. In a case report published this month in the journal Bipolar Disorders, they show that improvement in treatment resistant bipolar depression may involve repair of the leaky BBB via reversal of insulin resistance.

In November 2021, Dr. Calkin received a $50,000 grant from Dalhousie Medical Research Foundation, as part of the DMRF Influencers for Health Research program. Dr. Calkin is using these funds to help support another study that will further advance this critical health research outcome. The DMRF grant has allowed her to hire a research assistant and she has recruited three consented patients so far. The trial lasts 14-weeks and involves a brain scan, treatment with the drug metformin, and then another brain scan. All three patients who have received metformin went from being insulin resistant to being insulin sensitive and, more importantly, went into remission from their bipolar depression for the first time in decades. Results from their before and after treatment brain scans are pending.

Dr. Calkin is eager to let patients out there know about this life-changing study. Interested participants can text or leave a message with Claire at (902) 943-4753. 

Dr. Calkin stresses, “Patients out there need to know that there is hope.”

Dalhousie Medical Research Foundation created the DMRF Influencers for Health Research program to help foster a culture shift when it comes to philanthropy. Influencer donors are committed to improving health outcomes on a local, national, and global scale and fuel important health research that brings us closer to improved treatments, better access to healthcare, and cures for diseases.


For more information, please contact:

Christena Copeland
Director, Communications

Dalhousie Medical Research Foundation


About Dalhousie Medical Research Foundation:

For over 40 years, Dalhousie Medical Research Foundation has provided critical support to local health research by fundraising to attract the best resources available to bolster their leading-edge work. Whether it’s talent, equipment, training, or space, DMRF exists to strengthen this research to positively impact health outcomes regionally, nationally, and internationally. Since its founding in 1979, DMRF has provided health research at Dalhousie University with tens of millions of dollars in support.