Antibiotic repurposed to combat depression: UCalgary study

Researchers at the University of Calgary (U of C) are working on repurposing an antibiotic to improve the results of brain stimulation meant to defeat depression.

The antibiotic D-Cycloserine (DCS) helps magnetic stimulation (TMS) for people with major depressive disorder (MDD).

TMS is used to treat people who have treatment-resistant depression. However, it’s not effective on everyone and scientists suspect this could be due to an important process in the brain for memory and learning.

“We think TMS works by driving the brain to adapt to stimulation through a process called synaptic plasticity,” said Dr. Alexander McGirr, principal investigator on the study from U of C.

#UCalgary researchers supercharge brain stimulation by repurposing an antibiotic, leading to a new method to improve results of brain stimulation for people with major depressive disorder https://t.co/wmABHiYo4F @HotchkissBrain pic.twitter.com/aOCMlRoOzU

— U Calgary (@UCalgary) October 19, 2022

“One of the challenges, however, is that major depression is associated with reduced synaptic plasticity, and so TMS may be asking the depressed brain to adapt to stimulation in a way that it can not readily do. Adding D-Cycloserine to the TMS treatment appears to enhance TMS’s ability to drive synaptic plasticity and treat depression.”

The study examined participants for four weeks where they underwent TMS everyday. Also, half of them received DCS and the other half received a placebo.

The results were published in the JAMA Psychiatry and they show “almost 75 per cent of participants treated with DCS and TMS benefited, compared to only 30 per cent of those treated with TMS and a placebo.”

Meanwhile, the gold standard Montgomery Asberg Depression Rating Scale was used to measure depressive symptom severity.

“The combination treatment seemed to have benefits beyond depressive symptoms. The participants in this study that received DCS and TMS also had greater improvements in their symptoms of anxiety and overall well-being,” said study first author Jaeden Cole and a member of the McGirr lab.

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Fifty people were involved in the clinical trial, however, McGirr’s team plans to duplicate the research method with more participants to ensure clinical safety and efficacy of their experimental treatment.

“It is hard to convey how important this work could be for patients or the level of excitement that has been brewing since Dr. McGirr first presented these results,” said Dr. Valerie Taylor, head of the Department of Psychiatry at the Cumming School of Medicine.

‘This could change practice’ and treatment outcomes

“If confirmed, this could change practice and have a very significant impact on patients’ treatment outcomes.”

DCS has been researched in various psychiatric applications, including trauma and anxiety-related disorders. It’s also still used in the treatment of multidrug-resistant tuberculosis.

The drug is currently not available in Canada, however, additional research to back the efficacy of this combined treatment could contribute to its reintroduction in the country, according to McGirr.

The research was supported by the Brain and Behavior Research Foundation Young Investigator Award, and the Campus Alberta Innovates Program Chair in Neurostimulator. In addition, McGirr has a provisional patent filing for the combination of DCS and TMS in the treatment of depression.