50-year-old diabetes drug helps patients with bipolar disorder, study finds

A Halifax doctor's new approach to treatment-resistant bipolar disorder involves treating an underlying metabolic disorder to improve the psychiatric condition. 

Dr. Cindy Calkin said her research represents a paradigm shift in psychiatry and was recently published in the Journal of Clinical Psychiatry. She spent thousands of her own dollars to make it publicly available. 

Calkin worked as a family doctor for a decade before training as a psychiatrist. "I was told my medicine wouldn't be of any use to me, but it was a huge advantage because I could not stop treating the whole patient," she said. 

Bipolar disorder is a condition that causes dramatic mood swings, from depressed lows to manic episodes, along with changes in appetite and energy levels. 

It's typically treated with lithium, and anti-epilepsy, anti-psychotic and anti-depressant drugs. But many people find the drugs lose effectiveness after a few years, throwing them back into bipolar disorder. 

"What I was finding is it wasn't just patients with diabetes who had worse outcomes, it was other patients as well. I felt like there was something right in front of me that I was missing. And that ended up being insulin resistance," she told CBC News. 

She launched  a clinical trial in which people with treatment-resistant bipolar disorder were given metformin, a drug that's been used to treat diabetes in Canada for decades, to reverse insulin resistance. 

"Patients had been ill on average for 25 years," she said. "Most of these people had lost any hope of ever being better again."

Her research found 54 per cent of people who have bipolar also have insulin resistance, and half of those patients will be treatment resistant. 

The results were stunning. 

"By week six in the study, patients started to become well. And by week 14, which was study-end point, they remained well. And even 26 weeks out, they remained well."

MRI scans she did with Dr. Alon Friedman show a dramatic difference in one of her first patients. 

"So this one is an MRI of a patient who has extensive blood-brain barrier leakage. This is multiple [images] through his brain. And this is before treatment with metformin. He was insulin resistant and severely depressed. And this is three months on metformin. Blood-brain barrier has healed, he's no longer insulin resistant, and his depression has been in remission the last six years."

That barrier is supposed to keep viruses and bacteria out of the brain. "So I believe that patients with insulin resistance may have had inflammatory molecules crossing into the brain, making their brain disorder worse."

Metabolic psychiatry 

She compares it to how people once thought peptic ulcers were caused by stress, until two Australian researchers won a Nobel Prize in medicine for discovering a bacteria in the gut caused them.

"This is a paradigm shift in our field. This is a completely new way of approaching psychiatry."

Calkin said it's called metabolic psychiatry, a phrase coined by Dr. Shebani Sethi of Stanford University. 

An estimated 33,000 Maritimers suffer from treatment-resistant bipolar disorder. Worldwide, the number runs into the millions. Kellie Williams used to count herself among them. 

People had described her as "moody" for most of her life, and she was diagnosed with bipolar disorder in her late twenties. 

"My depression felt like if someone had passed away. That complete sadness, that complete despair. I would have this constant, all day long, and with no one passing away. I knew there was something very seriously wrong then," she said. 

The symptoms impacted her life with family, friends and at work. She struggled to keep plans, and she never knew when she would be incapacitated by a mood disorder. 

"There were some times, several times, where I contemplated suicide. To try and get rid of that despair or pain I felt, I actually started cutting as well, just to try and redirect that pain you feel inside in your head."

She saw Calkin's name on a bulletin board at a mental health clinic recruiting people with bipolar whose medication had stopped working. She was surprised when they tested her and told her she was insulin resistant. Calkin treated that condition, and the devastating disorder went away. Calkin thinks it lets the traditional drugs work again. 

"I couldn't believe it was actually gone. I'd never felt such a sense of wellness in my life," Williams said. "This is truly a miracle. I have my life — I want to say back, but I have my life better."

She's discovered she's an avid planner and loves filling her schedule up months in advance. 

She says her bipolar is in remission, and she's hopeful it will stay that way. She said others should feel hope, too.

"Don't be afraid to go out and do some research. Go online, ask people," she said. "You do have that right to be healthy and happy."

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