Dr. Kevin Reeves, MD, associate professor of clinical psychiatry and director of the interventional psychiatry service at Harding Hospital, talks about a new procedure that reduces symptoms of treatment resistant depression.
Interview conducted by Ivanhoe Broadcast News in April 2022.
What is treatment-resistant depression? How do you characterize it?
DR REEVES: Major depressive disorder is a very common condition and it’s one of the leading causes of disability worldwide. People notice that for a couple of weeks, they feel down emotionally, or they have low enjoyment. They’re maybe tired more or they can’t concentrate, things like that. For some people, the course of illness is a single episode during their life, and it resolves. For others, they may have periods of weeks, months, or years where they’re otherwise doing well, and then they have another episode. But a subset of people will have more regularly recurrent episodes in their life, or they may have more persistent symptoms for a couple of years in a row. So that’s kind of the course of the illness. When we talk about the treatments for the illness, it’s probably most accepted to say that if you have had at least a minimally effective dose of an oral antidepressant for at least four to six weeks, and you’ve had two of those trials without resolution of your depressive symptoms, that that would be a picture that we would call treatment-resistant depression.
When talk therapy or CBT medications aren’t working, what other options do patients have?
DR REEVES: Certainly, oral medications and talk therapy are the first line of treatments and they’re well accepted. But certain numbers of people, especially as you get into that kind of two antidepressants plus a trial of CBT, what we see is that right after at around the second trial, the numbers of people who experience a significant reduction in depressive symptoms, or their symptoms resolve altogether, starts to fall off drastically. So, that’s a point where we want to be able to offer more advanced therapies. This is the time we would start to think about noninvasive brain stimulation or other kinds of novel medications.
What is TMS and how does it work?
DR REEVES: Transcranial magnetic stimulation, or TMS, is a form of noninvasive brain stimulation that uses electromagnetic energy to stimulate networks within the brain. So, we would apply the energy across the skull to a patient who’s otherwise awake and resting comfortably. The energy is used by the nerves in the brain, the neurons, to either increase or decrease the amount of activity that they have. Then, that spreads throughout the connected neurons or the network within the brain.
Are there different ways to deliver that treatment?
DR REEVES: Absolutely, depending on things like the kind of coil that you use. The most widely used coil is a kind of a figure of eight coil. There are also a couple of other coils that are larger and broader that are used. Depending on the frequency, whether it’s faster or slower, you can modulate that brain activity either to increase or decrease activity. And you can use it in a very targeted way. So, there are different areas of the brain that we may choose to stimulate based on the symptoms that the person is having.
What’s the science behind this?
DR REEVES: When the neurons in the networks are working together, they’re communicating together. And when a person has had symptoms of depression or anxiety, over time, unfortunately, the brain learns and adapts to that, just like it would learn and adapt to positive situations. So, those networks can become reinforced towards unwanted or negative emotions to make them easier to experience over time. And so, using TMS or other noninvasive brain stimulation, the idea would be that stimulating the networks to function more normally would reinforce that healthier pattern of activity and shift the balance back towards what a person would like to be experiencing.
How is TMS different from ECT? Does it work along the same lines?
DR REEVES: Similar idea, still using external energy to stimulate the brain. The electrical fields that are generated with ECT are much larger so, more of the brain is being stimulated directly. That can be a helpful and unhelpful thing. Because there are parts of the brain, these networks that we want to stimulate, and then, parts of the brain that could lead to unwanted effects, disruptions in cognitive processes or even changes in, for example, heart rate or blood pressure. Because of the amount of brain that’s stimulated with ECT, if a person was not under anesthesia and with a muscle relaxant onboard, the motor areas of the brain would also be stimulated. So, there would be convulsions or muscle movements that, again, are not needed for the treatment but would be a kind of a byproduct. So, TMS does not have that sort of broad reach so, we can be much more targeted to the areas we’re stimulating.
Because TMS is much more targeted, is there less of a chance of side effects?
DR REEVES: Absolutely.
Less risk to patients?
DR REEVES: Absolutely. I think that that is one of the most attractive parts of TMS for patients. The magnetic field itself falls off in strength very quickly. So, almost below the jaw, there’s not a lot of energy that’s reaching any other part of the body. So, thyroid, heart, lung, liver, kidneys, none of those are experiencing any direct stimulation. What patients are going to notice is that there can be some mild, unpleasant sensations when the stimulation is happening, and that’s usually because of the nerves of the face are stimulated, as well. There may be some discomfort after or maybe a little bit of a headache. And in very rare cases, depending on the patient or their risk factors, it’s possible that there could be some seizure activity. But that’s so rare at this point that it’s not a significant risk.
How do you go about finding the exact point that needs to be stimulated?
DR REEVES: There are a couple of ways. One nice thing about TMS is you can see the results in real time. So, we are starting by stimulating parts of the brain that talk to the muscles through the spinal cord. When you apply a stimulation there, what you get is the person is going to notice a muscle contraction when they’re not telling themselves to do it. Using that kind of relationship, we can see how much stimulation is needed in the motor areas, and that will be applied to emotional centers, as well. The field of TMS continues to evolve very rapidly. We have a lot of very high-quality studies looking at, for example, MRI-guided treatment. We can use some of those studies to guide targeting in the office, just taking very simple measurements of the patient’s head, we can locate the areas we need.
Can you kind of walk us through the process?
DR REEVES: Absolutely. So, you notice the quickness, and we’re using a recently approved protocol called intermittent theta burst stimulation. This is a more patterned stimulation. So, when I took over the service in 2014, we were giving a single pulse 10 times a second for four seconds, it took usually close to 40 minutes. Theta burst stimulation uses three bursts with each pulse that’s given five times a second. This is based on some basic science that showed that this is closer to some of the nerves in the brain, how they would activate naturally. What we believe is that theta burst may be more efficient at causing those network changes that we talked about, that plasticity. You can deliver a therapeutic stimulation in about three minutes, which is, again, a far cry from close to 40 minutes. What you’re noticing is when Eric was in the chair, we had previously taken some individual measurements of his head, we knew where we were locating the coil based on that. So, we position that coil. And the movements that you were noticing is based on just the muscles that are near there. They’re being stimulated, too. But the NeuroStar advanced therapy system, with the head support that you saw, has some very precise measurements that allow us to be confident about our positioning of the coil. Those contact sensors that are on the coil itself allow us to make sure that the patient doesn’t lose contact with the device, and that’s a really helpful part of that specific system. It allows us to be very confident that the patient’s getting the same care each time.
What is it about this system that you’re using, the NeuroStar, that is a little bit more advanced than prior systems?
DR REEVES: So, we’ve used NeuroStar since we had the service. The things that I personally have liked about it is, number one, I think the positioning system is very good. I really appreciate the precision of having all those measurements to be able to say this is where it was the first time, we’re positioning it again each time. The coil itself is a more recent update. It’s cooled more efficiently so we can use these more advanced protocols effectively. So, I think that that system has been something over the years that has been upgradable and, as you might have known, they were able to publish one of the largest outcomes in TMS using a very large registry, so many people that are using the system. So, when I talk to patients about what they can expect, I can feel confident based on real world outcomes, based on this registry that I’m communicating with them.
How many sessions does it take before patients begin to feel a difference?
DR REEVES: So, Eric has had a couple different courses of TMS over time. And the longer that a person may be having symptoms before they see me, sometimes the more treatment they’ll need before they start to feel an improvement. Eric has been in a position where we know that this has worked for him and, in fact, other studies have shown that one of the possible ways to say to a patient this will likely work again is if they’ve had more TMS in the past. So, people that had TMS have had good results with it and tend to come back and it tends to continue to work. So, Eric noticed an improvement this time because I think we’ve been very good about interacting with him and making sure that we’re catching the symptoms early. For most of the patients that are seeing me, where they’ve had periods of months or years where they’ve had symptoms, I think we would hope to see small improvements even as early as the first week. We think usually that around 20 sessions is probably about the earliest time we could start to decide if this appears to be working or not.
What are other options? And is this in conjunction with medication? Are patients still on medication or does this replace their medication?
DR REEVES: So, TMS has antidepressant effects on its own. There are studies that were done to submit to the FDA on patients that had been washed out of their medicines. So, the patients are no problem. Patients don’t need to be on medicines for TMS to help. However, they may work together. So, in a small way, I think staying on your medicine probably will help outcomes for the patients.
What if the medications aren’t working with TMS?
DR REEVES: Other things that your doctor may have access to, especially depending on what setting they practice in, we would certainly be talking about if we should consider a trial of, for example, esketamine, which is a kind of a novel medication. Do we need to think about a more global brain stimulation like ECT? Or even a longer-term stimulation option like cervical vagus nerve stimulation, which is kind of an implanted device that can be active over months or years.
How much of a difference does TMS make for your patients? Have you seen a difference?
DR REEVES: I think that over the years, I have noticed a large improvement in patients. I think that not every patient will see a difference, but I would agree that most people are going to experience an improvement when they are treated with TMS. What you heard Eric say, I think, when patients talk about their benefits, they talk about being able to be more resilient under stress, being able to re-engage with their life. And I think that symptom improvement is one part of recovery. The other part is getting back to meaningful activities, relationships, and things like that. I think it can be very difficult to do that if you’re very depressed or anxious. But I would also say that that ability to be resilient under future stress is important. And I think that where we’re stimulating the brain goes along with that because these are areas that are involved in cognitive control of emotions. So, being able to filter emotions as they come up.
What portion of the brain is stimulated? How large is the proportion?
DR REEVES: Probably about the size of a quarter or a little less directly. The part that we’re looking at is a hub within a couple of different networks. So, from that spot, the communication is spreading throughout different emotional and cognitive networks.
What are the potential side effects?
DR REEVES: Discomfort under the coil, especially for those couple of seconds while the stimulation is happening, is one side effect. Most people are probably going to say that in terms of discomfort or intensity, it’s probably about a 5 out of 10 when they start. And then, over the couple of weeks, it will often reduce or fade, maybe 2, 2 1/2 out of 10 over time. That’s probably the most common thing. Some patients may experience some short headaches, half an hour or an hour after. And for the most part, that’s really it. As I said, the risk of seizures is very rare. We do screen patients for risk factors, including if they have any sort of metal in and around their head or if they have devices that are already being used to treat another condition. Those are things we would want to know about because the magnetic field could interact with those devices or that metal. In a way that could be harmful to the patient.
Is TMS covered by insurance? Does it hit a cap?
DR REEVES: So, most plans in 2022 are recognizing TMS as an approved therapy. And, in fact, we’re seeing many plans have scaled back the number of medications that they require before getting to TMS. So, certainly, when I started in 2014, it was routinely like, you needed to try at least four different medicines for at least a month or more. So, that’s a long time for people to get to. Now, many plans are down to about maybe one or two trials, which is a very helpful thing for people. In terms of a cap, what we see routinely is that many patients that receive TMS and do well are fairly stable for six months to a year out. But TMS is also an effective rescue treatment if symptoms would return. And many insurances will authorize retreatment if the patient would experience those symptoms again.
One thing that I noticed when Eric was having the procedure that he had, it was almost like a paper. What is that used for? Is that marking just measurements for the cap?
DR REEVES: That’s part of the head positioning system. It helps us to know that the patient is in the middle of the head support and that their head isn’t rotated one way or the other so that we would miss the stimulation. That precision in stimulation is a real benefit to the patient, but it can also be a challenge if you’re missing the spot. And patients will routinely say, hey, this doesn’t quite feel like where it was before. It’s helpful to have that positioning system and to reach back and say, OK, I guess maybe we kind of moved a little bit or something.
What is a theta burst?
DR REEVES: So, when the protocol that we use, the three-minute treatment, that pattern of stimulation that I mentioned, NeuroStar’s name for it is called TouchStar. That’s their designation for it, and that is FDA cleared protocol. Select few practices use the TouchStar, the FDA-cleared treatment protocol, with their NeuroStar Advanced Therapy system. Typical NeuroStar TMS delivers focused energy in short bursts in approximately 18 minutes. In general, that would be called theta burst stimulation. So, frequencies when the neurons fire at about five pulses per second is within what we call the theta range. So, there’s delta, theta, alpha, beta, and gamma. Those are names for speeds of neuronal firing. So, we’re giving a frequency five pulses a second within the theta range. But each pulse has three pulses of a burst within it, give it much faster. So, those two things together. So, it’s a burst pulse in the theta range, so theta burst.
What percentage of people with depression are treatment-resistant and may benefit from TMS?
DR REEVES: It’s probably about 1 in 3.
Is there anything else that you would want people to know, either about treating depression or about TMS or about this system?
DR REEVES: I think that it’s important that patients work with a physician or a nurse practitioner or someone that they trust and can feel open to talk about these things. We can’t help if we don’t know that they’re experiencing the symptoms. And again, I think that we want to act as early as possible within their course of illness to avoid the months and years that some people are suffering. And realizing that if there have been trials of medication and talk therapy that aren’t helping the patient like they would hope and they’ve given it a good effort, they’re at a good dose for at least a month. They need to be aware that there are other very effective options. And these options are going to be open to them as more psychiatrists can provide them. Being proactive is only going to reduce the time that they’re spending suffering and I think will help us to treat them more effectively.
END OF INTERVIEW
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