New clinic offers alternative options for treatment-resistant depression

Stephen Manlove, M.D., has been a psychiatrist for decades, but some years ago, he almost stepped away from the profession for good.

He’d seen too many people struggle to find an effective treatment for their clinical depression. While commonly available antidepressants helped a percentage of his patients, there were many others who did not seem to benefit from the classic pharmacological approach. It felt frustrating to not be able to help the very people who so desperately needed his support.

“Around 2013 or 2014, I was thinking I should do something different, maybe wrap it up,” Manlove said. “I thought seriously about retiring at that point, of going in a different direction.”

But, as he talked through his frustrations with trusted friends and colleagues, Manlove came to a realization: “I concluded that what I really like to do is to treat people I haven’t been able to treat before. Psychiatry has gotten so limited to medication treatment, and I thought there has to be different things we could do.”

Instead of stepping away from psychiatry, Manlove instead decided to reinvigorate his Rapid City, South Dakota-based practice, offering patients the option of treating their mental illness with promising new therapies, including transcranial magnetic stimulation (TMS), a noninvasive procedure using magnetic fields to stimulate brain cells to improve symptoms of depression.

“At that point TMS was just coming out,” Manlove said. “I thought, ‘Maybe this is a way to help patients with treatment-resistant depression.’” He started offering TMS to his patients, and the results were overwhelmingly positive.

“It was one of the most incredibly satisfying things to see people who have been depressed for a long time get better. It is like magic.” When TMS works, he said, “It is as dramatic a change that you’ll see in the whole psychiatric world. It is incredibly rewarding.”

As he began to see his patients respond positively to TMS, Manlove decided to further expand his approach to depression treatment. He’d long known about the connection between physical and mental health, so he began encouraging his patients to make gradual lifestyle changes that could further support their recovery. He also trained his technicians to coach patients during treatment sessions.

“We found that when we addressed lifestyle plus medical issues that were somewhat normal and did TMS we got a better response than other places,” Manlove said. “Our recidivism rate was really low.”

Manlove’s interest in alternative therapies for depression eventually led him to research highlighting the promise of ketamine, a commonly used anesthetic and sometime party drug that has shown promise in treating severe depression. When administered under the guidance of a medical professional, ketamine was shown to significantly reduce depressive symptoms and suicidal ideation in patients. Like TMS, ketamine, when administered correctly, has few negative side effects, an issue that often plagued individuals treated with classic antidepressant or antipsychotic medications.

This felt like a promising new approach. Ketamine, Manlove explained, “added another tool. For years, the problem really had been the limited number of people who respond to medications for depression. I was interested in expanding my treatment options.”

A little over a year ago, Manlove was attending a meeting for mental health providers in  Minneapolis when he struck up a conversation with a fellow attendee. When he told her about his interest in taking a new approach to depression treatment, her eyes lit up.

“She said,” Manlove recalled, “‘You should meet my husband. He thinks differently than other psychiatrists.’”

The woman’s husband was Brian Johns, M.D., a psychiatrist based at North Memorial Hospital in Robbinsdale. Johns had been using ketamine to treat patients with severe depression at North Memorial and at the Minneapolis VA, and had even co-authored a study on the approach.

Manlove called Johns and the two began discussing the possibility of a partnership, of opening a Twin Cities-based clinic that would bring Manlove’s approach to depression treatment to a wider audience in a larger metropolitan area.

Finding another psychiatrist interested in taking an alternative approach to the treatment of severe depression felt promising, Manlove said. The possibility of offering those treatments to a larger number of patients was exciting.

“I’ve practiced for a long time,” Manlove said. “I used the standard treatments. The people you remember at the end of the day are the ones who don’t get better. That’s frustrating and discouraging and makes you want to do better.”

He’d seen the positive impact that TMS and ketamine had on patients who had all but given up hope of ever recovering from their depression, and he wanted to offer that option to more people than he’d been able to reach in South Dakota. Maybe this new partnership would help him do that, he said: “There are few things more fun in my life than seeing a depressed person come alive and feel good again.”

Pandemic pause, then moving forward

Before Manlove and Johns could get their clinic off the ground, their plans were thrown off course by the emergence of a global pandemic. “That was a big hurdle,” Manlove said. “The world was vibrating in a funny way, so we decided to put the project on pause.”

The two potential business partners weren’t sure how they could operate a mental health clinic during a global shutdown, but then, as states and insurers began to loosen regulations around the practice of telepsychiatry, the pair realized that this might actually be the perfect time to launch a new practice.

“One of the things that happened with this pandemic was we all got better at communicating by televideo,” Manlove said. With remote meeting technology, he continued:  “We thought it would be easier to do a clinic that straddled Rapid City and the Twin Cities. We realized that there are a lot of people in the Twin Cities who would be willing to do telemedicine for their regular appointments and then come in person to do TMS.”

Johns was excited about the possibility of creating an independent clinic that could offer a range of treatment options to patients. Ketamine, while it showed great promise in the treatment of severe depression, was hampered by insurance companies’ reluctance to cover a use still considered experimental. He dreamed about opening a clinic that would offer ketamine as an affordable option for people in need.

Other than in inpatient mental health programs, Johns said, ketamine treatments for severe depression are available in the Twin Cities primarily at cash-only clinics run by providers without extensive backgrounds in the treatment of mental illness.

“Most of the ketamine clinics in the Twin Cities are run by anesthetists or certified nurse anesthetists,” he said. “They are trained to administer anesthetics. But they don’t know if it is indicated or warranted or even potentially dangerous for those patients to receive ketamine.”

Johns said that his and Manlove’s Minnetonka-based clinic — which they have named Advanced Brain + Body Clinic — will be different. Since the FDA has approved Spravato, a ketamine-based medication intended for the treatment of major depressive disorder with suicidal thoughts or actions, more insurance companies are now covering the drug. He said that he and Manlove are committed to helping their patients have their treatments covered by insurance. The clinic is scheduling virtual appointments and will open officially for in-person treatment on April 6.

“It will be different at our clinic,” Johns said. “We are going to accept all insurance.”

While Manlove said that he cannot predict if all insurance companies will cover treatments like ketamine or TMS, he, Johns and their staff will focus on making the treatments affordable. “Our No. 1 goal is to treat people,” he said. “We will do our very best to figure out a way to do that within their financial means.”

Johns has deep experience in ketamine treatment, building from his work with patients at North Memorial and the Minneapolis VA.

“I currently have about four dozen patients who are receiving ketamine treatment,” Johns said. “They have been taking it for several years. Some do both ketamine and TMS. They find it is really helpful.”

Just as at Manlove’s Rapid City practice, patients at Advanced Brain + Body Clinic in the Twin Cities will also be treated from a whole-body approach. In intake sessions, providers will work with patients to establish health and wellness goals, which they will later discuss during ketamine and TMS treatment sessions, which can last anywhere from 30 minutes to two hours.

“We see people a lot,” Manlove said. “It’s every day for five weeks for TMS and for ketamine it’s at least weekly. We have a lot of time to talk to people. We have a lot of access to people’s stories.”

A good example is one patient that Manlove saw in his Rapid City office.

“When we were talking about goal setting, he said, ‘I’d like to be able to run three miles without stopping.’ I said, ‘We can work with you on that.’ We make goals and we talk people through them. If somebody isn’t doing anything, I’ll say, ‘Let’s start by walking out to the mailbox and back.’ We know that helping your body helps your mind. We want to help our patients make that connection.”

Johns’ study on ketamine cemented his belief that the medication, when administered under the guidance of a trained practitioner, can be almost miraculous in the way it brings severely depressed people back to life.

Johns’ study was the first to use ketamine as an outpatient medication.

“In the past,” he explained, “people have been hospitalized during treatment just to make sure that the ketamine was having an effect. We knew it worked. We didn’t know if it worked in a real-world scenario. So we had patients come in,  do an infusion, go home.”

‘Overwhelmingly positive’

Study participants — about a dozen, according to Johns — were kept on their other medications. The results, he said, “were phenomenal. Ninety-two percent had a response. It was pretty impressive to see people who had not responded to any other medication get 50 percent or more better. Sixty-seven percent of participants reported no symptoms of depression after repeated infusions of ketamine.”

This remarkably successful response can be explained in part, Johns said, by the brain’s reaction to the drug.

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“Ketamine grows neurons within hours of treatment. It’s like Miracle-Gro for your brain.” And, unlike other antidepressant medications, Johns said, for many people, ketamine works quickly: “Some people can have a single infusion of ketamine and say, ‘I don’t have any suicidal thoughts.’”

Before Johns’ research, ketamine had only been studied as a one-time treatment. The research team at the VA thought that repeated infusions could be even more effective. With a single infusion of ketamine, Johns explained, researchers were “seeing response rates of up to 30 percent after an infusion. We thought, ‘What happens if we do it over and over again for two weeks and then follow up?’ We found that some people were fast responders — and some were slow responders who needed five or six infusions before they had a response. After several infusions, the response was overwhelmingly positive.”

At Advanced Brain + Body Clinic, Johns said, patients will be offered a number of ways to receive ketamine doses.

“I’ll be prescribing ketamine orally, intranasally, intravenously and intramuscularly,” he said. “We will be the only clinic to offer those different options. Some patients might respond better to different approaches. We want to offer them all.”

Johns said that taking this open-mined approach to the treatment of serious depression is the best — and maybe only — approach that seems appropriate. Since so many people do not see relief from their depressive symptoms through the use of commonly prescribed drugs, psychiatrists should be open to trying a new approach, he said. Sticking with the accepted way of treatment just leaves too many people without acceptable results.

“It’s not enough when 30 percent or more of patients are treatment resistant,” Johns said. “If you can only treat two out of three people with depression successfully, you have a really bad batting average. As physicians, what we want to do what we’re trained to do, which is to help people. We’re always looking for ways to help improve that batting average. If it will help, I’m always open to trying other options.”

After decades of struggle, now ‘opening up’

Ever since he was a teenager, Jon Mattila struggled with debilitating anxiety and depression.

“If you asked me how many kinds of pills I’ve taken over the years, I can’t answer that,” said the 53-year-old Bemidji resident. “Maybe 30 or 40?”

Mattila’s wife, Lisa, is all too familiar with her husband’s mental health struggles. The two met and married when they were teenagers, and through their long marriage, Lisa has supported Jon through countless treatments, including talk therapy, dialectical behavior therapy (DBT), electroconvulsive therapy (ECT), an alternative treatment involving tattoos, and several courses of classic antidepressant and antianxiety medications. None worked to ease Jon’s depression, and in 2017, Lisa said, an adverse reaction to one medication almost killed him.

Though he couldn’t help but feel discouraged by his unsuccessful treatments, Jon kept trying to find a therapy that would help ease his symptoms.

“He’s been trying to do his best to keep on going because his depression has been pretty profound,” Lisa said. “He’ll try anything because he’s that desperate.”

A licensed professional nurse (LPN) who works with psychiatric patients, Lisa is always on the lookout for new therapies that might help her husband. When she heard about ketamine and its success in treating people with severe depression and suicidal ideation, she made it her mission to get Jon signed up for the treatment.

“I started calling my insurance company and asking them to see if they could find a doctor who prescribed ketamine,” Lisa said. “They did a bunch of searches for me until they found Dr. Brian Johns.”

The fact that Johns is based in Minneapolis didn’t stop the Mattilas. They scheduled an appointment, and made the long drive down to the Twin Cities.

Johns eventually prescribed daily intranasal doses of ketamine to be administered at home under Lisa’s observation. Jon Mattila said he felt a subtle lift in his mood after the first time he took the medication.

“The ketamine worked out really well for me,” Jon said. “You feel it fairly well on your first dose.” Before he started taking the drug, which Advanced Brain + Body offers in a single-dose form compounded by a local pharmacist, he continued, “my anxiety was a pretty constant thing. When I take ketamine, it gives me a punch right away. Then it fades out, and you start feeling better.”

Lisa said she has seen significant change in her husband since he started on his daily ketamine treatment. “He was able to start opening up and he even started suggesting that we do things or talk about things,” she said. The couple even purchased a hot tub and installed it in backyard so they can soak together and just talk. It’s been an amazing development, Lisa said: “This was a person who has been closed down for many years.”

“Jon,” Lisa continued, “lives with a very dark depression. Ketamine has made things lighter.” The couple’s children and grandchildren notice the change, too: “He’s been able to do his dad roles and his grandpa roles. It’s made a big difference in all of our lives.”

Johns said that there has been little research on the benefits of ongoing ketamine therapy. But he believes that in cases like Jon Mattila’s, daily dosing can make all the difference in the world.

“There aren’t many maintenance studies,” Johns said. “I don’t think any mediation is a one-and-done thing. I have seen people use it to get out of the deep suicidal hole they are in and then do work and be able to walk away and be done with it. I’ve also seen people who need to use it every day. It is really individualized.”

Jon Mattila said he accepts that he’ll always live with some level of mental illness, but he’s encouraged by the results he’s seen with ketamine therapy. He will continue to see a therapist as well as pay close attention to his physical health, but at the moment he feels that his life is heading in a good direction for the first time in years.

“When I went to therapy today, I realized that I had no suicidal thoughts,” Jon said. This is a significant change. “Ketamine helps my anxiety. It does help tamp down the depression a little bit, too.”

Jon isn’t a big talker, so he paused for a long moment before adding, “If someone asked me what It thought, I’d be an advocate for ketamine. I think it helps. It stopped me from being dead.”