TBI/PTSD9 Larry Minikes TBI/PTSD9 Larry Minikes

Nitrous oxide may bring relief to veterans suffering from PTSD

July 7, 2020

Science Daily/University of Chicago Medical Center

A small pilot study provides an early glimpse of how some veterans struggling with PTSD may benefit from one simple, inexpensive treatment involving nitrous oxide, commonly known as laughing gas.

For military veterans suffering from post-traumatic stress disorder (PTSD), symptoms such as anxiety, anger and depression can have a devastating impact on their health, daily routine, relationships and overall quality of life.

A new pilot study by the University of Chicago Medicine and the Stanford University School of Medicine team from the VA Palo Alto Health Care System (principal investigators Carolyn Rodriguez, MD, and David Clark, MD, PhD) provides an early glimpse of how some of these veterans may benefit from one simple, inexpensive treatment involving nitrous oxide, commonly known as laughing gas.

"Effective treatments for PTSD are limited," said anesthesiologist Peter Nagele, MD, chair of the Department of Anesthesia & Critical Care at UChicago Medicine and co-author of the paper. "While small in scale, this study shows the early promise of using nitrous oxide to quickly relieve symptoms of PTSD."

The findings, based on a study of three military veterans suffering from PTSD and published June 30 in the Journal of Clinical Psychiatry, could lead to improved treatments for a psychiatric disorder that has affected thousands of current and former members of the U.S. military.

For this new study, three veterans with PTSD were asked to inhale a single one-hour dose of 50% nitrous oxide and 50% oxygen through a face mask. Within hours after breathing nitrous oxide, two of the patients reported a marked improvement in their PTSD symptoms. This improvement lasted one week for one of the patients, while the other patient's symptoms gradually returned over the week. The third patient reported an improvement two hours after his treatment but went back to experiencing symptoms the next day.

"Like many other treatments, nitrous oxide appears to be effective for some patients but not for others," explained Nagele, who is himself a veteran of the Austrian Army and grateful to have identified an opportunity to help other veterans. "Often drugs work only on a subset of patients, while others do not respond. It's our role to determine who may benefit from this treatment, and who won't."

Nagele is a pioneer in the field of using nitrous oxide to treat depression. Most commonly known for its use by dentists, nitrous oxide is a low-cost, easy-to-use medication. Although some patients may experience side effects like nausea or vomiting while receiving nitrous oxide, the reactions are temporary.

Exactly how and why nitrous oxide relieves symptoms of depression in some people has yet to be fully understood. Most traditional antidepressants work through a brain chemical called serotonin. Nitrous oxide, like ketamine, an anesthetic that recently received FDA-approval in a nasal spray form to treat major depression, works through a different mechanism, by blocking N-methyl-D-aspartate (NMDA) receptors.

A 2015 landmark study by Nagele found that two-thirds of patients with treatment-resistant depression experienced an improvement in symptoms after receiving nitrous oxide.

For his next study, Nagele is researching the ideal dose of nitrous oxide to treat intractable depression. Study participants with treatment-resistant depression received different doses of nitrous oxide so that Nagele and his team could compare each dose's effectiveness and side effects. The study is being funded by the Brain & Behavior Research Foundation.

"Does nitrous oxide help veterans with post traumatic stress disorder" was funded by the VA Office of Research and Development Clinical Science Research & Development Service.

https://www.sciencedaily.com/releases/2020/07/200702113647.htm

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Health/Wellness9 Larry Minikes Health/Wellness9 Larry Minikes

Research leads to life changing improvement for some people living with depression

Deep brain stimulation study targets people with treatment-resistant depression

January 27, 2020

Science Daily/University of Calgary

Researchers have completed a study investigating the effects of two different methods of deep brain stimulation (DBS), short pulse and long pulse, for treatment-resistant depression. The findings showed that both methods of stimulation were equally safe and effective in reducing depressive symptoms. Some study participants have experienced a massive positive change in their lives.

Beth MacKay knew at a young age that she saw the world differently than many of her friends and family. She thought her pessimism and cynicism were rooted in realism, a proud reminder of her Scottish roots, and not a sign of an underlying medical condition. But, that understanding of herself changed when at the age of 17, she attempted suicide.

"I was diagnosed with depression, but looking back, it started much earlier," says MacKay, now 31. "Doctors believe it may have started when I was 10 or 11-years-old. As a child I would go through periods where I couldn't sleep, I didn't want to go to school, and I was constantly sick."

MacKay's parents tried to find help and support for her. They thought her symptoms may have been related to a learning disorder, but no one suspected depression could be the cause.

Prescribed anti-depressants and therapy, MacKay went on to university. She noticed everyone around her seemed to be functioning, but she couldn't get out of bed. She spent the next several years pretending to be okay. She would sleep most of the day, and get up-and-out only long enough to put on a front to show people she was fine. It seemed that no matter what treatment options she tried nothing made life manageable.

"Everyday felt like climbing up a mountain. Something as simple as showering, doing dishes or throwing in a load of a laundry felt too difficult at times," recalls MacKay.

Always open to trying something else to improve her life, MacKay volunteered for a research study at the University of Calgary. Dr. Rajamannar Ramasubbu, MD, was investigating the effects of two different methods of deep brain stimulation (DBS), short pulse and long pulse, for treatment-resistant depression.

"It can be very difficult to find study participants for research like this," says Ramasubbu, a professor in the departments of Psychiatry and Clinical Neurosciences, and member of The Mathison Centre for Mental Health Research & Education and the Hotchkiss Brain Institute at the Cumming School of Medicine (CSM). "The procedure is invasive, so many clinicians are reluctant to recommend it. It requires implanting an electrode into the brain that is connected to a pulse generator that is implanted under the clavicle into the chest."

Just as pacemakers deliver electrical impulses to help control abnormal heart rhythms, DBS devices deliver electrical impulses to help neurons (brain cells) within the brain communicate more efficiently with each other.

"Depression is caused by abnormalities in the neural circuit responsible for emotional regulation," says Ramasubbu. "The region of the brain we target (subcallosal cingulate) is the junction of the limbic and frontal regions. Stimulating this area helps to keep a balance between these two unique systems."

Multi-disciplinary team collaborates on DBS study

Participants are awake when the device is implanted. Dr. Zelma Kiss, MD/PhD, a neurosurgeon and co- principal investigator of the study performed the procedure at the Foothills Medical Centre (FMC).

Participants were randomized into two groups, one group received short pulse stimulation, the other long pulse width stimulation. After six months, treatment switched for those who did not respond in the first six months. Researchers used the Hamilton Depression Rating Scale to measure change in symptoms.

"Both methods of stimulation were equally safe and effective in reducing depressive symptoms," says Ramasubbu. "50 per cent of the participants responded to the stimulation with 50 per cent reduction in symptoms. Of which 30 per cent experienced complete improvement in their symptoms, especially those who received long pulse width stimulation."

MacKay says she's experienced a massive change. "Basically I was nearly dead and now I'm mostly alive. I'm still figuring out what life feels like, because it feels so different and so much better than before the implant."

Ramasubbu adds more research is needed to determine which patients with treatment resistant depression will benefit from DBS. Study participants ranged in age from 20 to 70, with younger participants showing better improvement than older participants.

https://www.sciencedaily.com/releases/2020/01/200127164325.htm

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