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Patient Selection and Engagement
HIGHLIGHTS
- Success in deep brain stimulation depends to a great degree upon selecting the correct patient. (Candelario-Mckeown)
- It is vital to educate a patient on what to expect from the deep brain stimulation surgery and afterward, as this can have a major effect on the patient’s satisfaction and behavior. Clear communication between a patient and providers is crucial. (Perides, Wang)
- Support systems (e.g., family, caregiver, and friends) for a patient are also an important factor in the success of deep brain stimulation. (Davis)
- Biomarkers can signal to clinicians and patients that a deep brain stimulation surgery has had its desired effect even before the surgery’s effects on the patient’s symptoms are apparent. (Widge)
- DBS used for psychiatric disorders such as depression or obsessive-compulsive disorder may be seen as rehabilitative rather than curative. That is, in most cases it will not get rid of symptoms, but it may make them easier for a patient to manage. (Widge)
NOTE: This list is the rapporteurs’ summary of points made by the individual speakers identified, and the statements have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They are not intended to reflect a consensus among workshop participants.
Decisions regarding which patients should be offered the option to undergo deep brain stimulation (DBS) can impact the overall effectiveness of the treatment, said Sarah Perides, a pediatric practitioner at the Evelina London Children’s Hospital and Patron at the Deep Brain Stimulation Nurses Association: “I think patient selection is one of the most important, if not the most important, aspect about managing patients with implantable devices.” Furthermore, the decisions and actions of individual patients will also play a role in determining how widely adopted DBS technologies may become in the future.
Good patient selection is very challenging, Perides continued. She said, “You need to find the right patient . . . clinically, phenotypically, biologically, psychologically, and socially. You also need to know what patients are not good for this type of surgery.” Then, once a patient is selected, the clinician must build an effective relationship not only with the patient but also their family, partner, and local care team. The clinician must have open conversations with the patient about the procedure risks, potential benefits, and long-term implications. “No matter what the outcome is—good, bad, or ugly—you need to maintain that relationship. It is not a do-and-discharge therapy. You have a long-term relationship with the patient, whatever the outcome.”
With that background, several workshop participants reviewed the challenges associated with patient selection and engagement to consider the ethics of ensuring access to all patients and demographics; explored the potential opportunities and collaborations needed to develop informed patient selection practices and equitable access to the technology; and reviewed patients’ concerns about possible complications of implantable brain stimulation and how best to inform patients about those complications.
PATIENT SELECTION IN THE UNITED KINGDOM’S NATIONAL HEALTH SERVICE
Joseph Candelario-Mckeown is a nurse practitioner at the National Hospital for Neurology and Neurosurgery in London with more than 17 years of experience using DBS to treat Parkinson’s disease, among other areas. He said that success in DBS relies heavily on selecting the right patient at the right time in terms of when the surgery is carried out. Making the correct decision requires a multidisciplinary approach with expert clinicians who know what they are doing, Candelario-Mckeown said, and it is also important to listen to the patients in the time leading up to the surgery. In the United Kingdom there are specialized nurses to look after patients undergoing DBS and to serve as the first point of contact. “We have put the patient at the very center of their care,” he said.
To determine which patients qualify for DBS surgery, the United Kingdom’s National Health Service uses a number of objective clinical criteria,
Candelario-Mckeown said. In the case of Parkinson’s disease, these include such things as the patient having had the disease for a minimum of 5 years, Levodopa responsiveness,1 a cognitive and neuropsychology assessment, neuroimaging, and a psychiatric assessment. In addition to assessing the need for the surgery, the criteria are also meant to assess the likely short- and long-term outcomes of the surgery and whether it would offer the patient a positive or negative outcome. The predictive criteria include age, quality of life, the disease phenotype, genetic information, and comorbidities.
As a nurse practitioner, Candelario-Mckeown said, one of his jobs is to understand patient expectations and motivations. Why are they getting the surgery? What do they expect to gain? He also educates patients and their families about what they can expect from DBS, such as what improvements are likely and how long it will take to optimize the settings of the device.
BARRIERS TO RECEIVING DEEP BRAIN STIMULATION
Rachel Davis, an associate professor of psychiatry at the University of Colorado Anschutz School of Medicine, spoke about four main barriers to getting DBS surgery, using obsessive-compulsive disorder (OCD) as an example. One barrier is limited access to specialized prerequisite treatment. “It is hard for people to find psychiatric care covered by insurance, let alone specific OCD expert care,” she said. “We in Colorado have one of the few centers that accept insurance and provide expert OCD treatment. However, the more patients we see, the more money we lose, and the more we are at the mercy of our hospital and our department of psychiatry to keep us afloat.” Her department had about 100 people on its wait list for therapy at the time of the workshop, she added.
This barrier combines with two others—a lack of insurance authorization and reimbursement and a lack of access to specialized treatment centers—to dramatically limit the number of patients who receive DBS to treat OCD, Davis said. Since the U.S. Food and Drug Administration (FDA) approved DBS for the treatment of OCD in 2009, there have been fewer than 400 DBS surgeries worldwide in patients with OCD. “You can compare this to approximately 160,000 surgeries for Parkinson’s disease,” she added. And without enough surgeries, it is impossible for doctors and clinics to develop expertise at treating OCD with DBS. “Right now, there are only a handful of centers in the U.S. that offer deep brain stimulation for OCD or psychiatric indications in general,” Davis said.
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1 In most patients with Parkinson’s disease, treatment with levodopa, the precursor to dopamine, acts to reduce various symptoms of the disease, such as bradykinesia, or the slowing of movement that is one of the disease’s main symptoms. How a Parkinson’s patient responds to levodopa provides information about the likely underlying neuronal deficits that are causing the disease. See Kempster et al. (2007).
The fourth barrier Davis mentioned was stigma and how stigma regarding surgery for mental health issues is still left over from earlier attitudes. In the mid-1900s, she explained, there were few medications to treat psychiatric illness, so doctors used brain surgery or lobotomy. “Brain surgery back then was often indiscriminately done, grossly destructive, and not very effective,” she said, and “it became associated with inhumane treatment of people who were mentally ill.” Brain surgery is very different today with much more attention being given to ethical and medically appropriate use, she continued, “but that stigma is still there.” And that stigma probably ends up limiting referrals from some physicians who do not consider neurosurgery a reasonable option for the treatment of mental illness.
To conclude, she spoke briefly about the importance of support systems both pre- and post-operation. “DBS requires not only individual buy-in but family or support system buy-in,” she said. “You want to make sure that the family [and support system] has all their questions answered. If the patient is on board but the family is suspicious, that can interfere with outcomes and impede recovery. You also want to be sure family is available for support postoperatively.” For example, some patients with OCD have problems maintaining appropriate hygiene after the surgery because of their extensive shower rituals, which can increase infection. “Involving your family to ensure adequate hygiene, nutrition, and postoperative wound care can be important,” she said.
HELPING PATIENTS DECIDE WHETHER TO HAVE DEEP BRAIN STIMULATION SURGERY
Doris Wang, an associate professor in the Department of Neurological Surgery at the University of California, San Francisco, is a neurosurgeon who specializes in providing DBS for patient with movement disorders. She spoke about helping patients determine whether DBS surgery is right for them and how to optimize surgical outcomes.
“By the time patients get to me for surgical evaluation,” she said, “they have been living with their movement disorders for many years. It is a big step to go from dealing with a chronic illness for which your symptoms may be partially managed by taking pills to having your head opened and all these electronics implanted in your brain.” Some patients, particularly those who have spoken with others who have had good results from the procedure, cannot wait to get a potentially life-changing surgery. Others see it as a “big scary thing” that they are exploring at the request of their doctors or as a last resort.
In speaking with patients, she said, she has several goals. The first is to explain the surgery: what is being implanted, the steps of the surgical procedure, the risks, the length of the associated hospital stay, and so on.
Second, she wants the patient to have the correct expectations about what will and will not improve with the surgery. It is important that the patient understand, for instance, that DBS does not cure the disease or stop its progression. Third, she wants to learn about the patient’s preferences in order to personalize the surgery. Would the patient prefer to be asleep or awake? Would the patient prefer the incision-less option? Or would the patient prefer to forgo the surgery altogether and choose a less invasive way to treat the symptoms?
Finally, Wang said, she has learned that there are several factors important to optimizing the outcome of DBS surgeries. The most important factor is patient selection—making sure, for example, that the patient has been diagnosed correctly, that the patient’s major motor symptoms are at least somewhat responsive to medication, that psychiatric and neurological comorbidities are not too bothersome, and that the patient has adequate social support.
Second, she provides clear expectations so that the patient does not have unrealistic hopes for improvement. The third factor in optimizing outcome is practicing good surgical techniques. She does everything in her power, she said, to place the electrodes accurately and safely. “That comes from years of practice and surgical technique,” she explained.
Fourth, she tries to anticipate potential problems and have contingency plans in place. Finally, she said, clear communication with patients is key to good outcomes. “Even if I do the perfect job, sometimes patients still don’t have the perfect or expected outcome,” Wang said. “If patients don’t have what they need, then we go and explore what the issue is. Is it because the leads are not placed well? Is it because they haven’t undergone adequate programming?” By communicating clearly with patients and other members of the team, such problems can be identified and solved, she added.
PROGRAMMING DEEP BRAIN STIMULATION IMPLANTS TO IMPROVE OUTCOMES
Alik Widge, an associate professor of psychiatry at the University of Minnesota, where he directs the Translational NeuroEngineering Laboratory, spoke about improving DBS outcomes by learning to do a better job of programming the implants. “If we really want to get patients enthusiastic and payers enthusiastic about scaling up innovative brain stimulation,” he said, “we have to be able to tell people that we know when this is going to work for you, and we know we are doing it right.” The key to that, he continued, “is to get way more objective about what we are doing with programming,” and the key to that, in turn, is to use biomarkers to provide an objective measure of the results of DBS.
Widge offered an example of how biomarker use can improve results from deep brain stimulation. The example involved the treatment of major depressive disorder (MDD) and OCD, but it is much more broadly applicable, he said.
One area in the brain that has been identified as a potential DBS target in treating MDD is the ventral capsule/ventral striatum. The FDA has approved DBS in that area for treating OCD (Denys et al., 2020), and several research groups have investigated it in the treatment of MDD, but the results have varied wildly. One industry-sponsored trial (Dougherty et al., 2015) saw no effect on depression from this treatment, Widge said, while another academic trial (Bergfeld et al., 2016) reported a large effect. What was the difference? The first trial lasted just 4 months and used a standard algorithm for DBS, almost “set it and forget it.” The second one, by contrast, gave an expert clinician a year of trial and error to try to figure out how to help these patients, working with the settings and observing the results. The moral, he said, is that with time, experimentation, and clinical expertise, outcomes can get much better.
A major problem with such an approach is that it is very hard to measure outcomes, Widge said. In the best cases, such as the one described previously by Jon Nelson, the improvement may be obvious immediately, but more commonly, it will often take weeks to months for an effect to appear. “That means patients are sitting there saying, ‘Am I going to get better? Do you have any clue? Do you really know what you are doing? Is my stimulator on? Is it in the right place?’”
Given this situation, Widge and his colleagues are looking for ways to measure changes in the brain that will predict improvement even if that improvement will not appear for weeks or months. In particular, they are focusing on a particular biomarker known as cognitive control, which is the ability to inhibit responses—in essence, a person’s ability to refrain from what would be a default or habitual behavior, such as resisting the urge to eat a candy bar when on a diet. Cognitive control is impaired in a number of disorders, Widge explained, including depression, OCD, and addiction, and it can be measured objectively.
What Widge’s team discovered is that DBS of the ventral capsule/ventral striatum improves cognitive control, and the effect is measurable within a few seconds of a change in stimulation (Basu et al., 2023; Widge et al., 2019). Thus, he suggested, it may serve as a biomarker that predicts whether DBS will improve psychiatric symptoms in a patient (Nagrale et al., 2023). This would provide a “decision support system” to a clinician that will indicate when the proper target in the brain has been fully engaged. It could also give patients confidence that a treatment has made a difference in their brain, even if they cannot yet sense the difference themselves.
Widge also spoke about the challenge of using biomarkers in a clinical setting. Clinicians often have to juggle many responsibilities, so a simpler technology can be important for usability in the clinic. However, academic doctors often seek out technologies that provide them with more control over the settings and output. This means that it is a challenge to figure out how to take complex knowledge and procedures developed by academic doctors—such as the use of biomarkers—and translate them into something that clinicians will use. Technology or biomarkers that are too complex may prevent widespread usability by clinicians and decrease accessibility to patients.
Finally, Widge said that it is important to see psychiatric DBS as rehabilitative. In treating something like tremors caused by Parkinson’s disease, he thinks of it as curative, he said. “Put on the stimulator, turn it on, the symptom goes away.” But, he continued, “in mental health we are learning it is not curative but rehabilitative. What we are doing is helping patients benefit from the intensive psychosocial therapies that you heard some patients talk about. This is a different model for psychiatry.” Patients may feel more able to ignore their symptoms, even if the symptoms still exist. This is very different from classic ideas about changing mood or eliminating thoughts, he said, and it will be important to determine how best to talk to patients to explain to them what to expect.
DISCUSSION
Perides asked whether poor patient selection affects outcomes and overall patient engagement and satisfaction. “Yes,” Candelario-Mckeown responded, “I have seen patients I thought who would have done better if we were careful identifying problems we should have known.” In particular, he mentioned nonmotor symptoms (e.g., mental health, pain, restless legs, speech and communication problems) that end up being overlooked because of the focus on motor symptoms such as trembling.
The Impact of Data Collection and Outcomes on Patient Perception
Perides then asked the panelists whether DBS patients are worried about the fact that clinicians collect a great deal of data about them and their brain function and whether perhaps such worries affect their decisions on whether to get the procedure. Widge said he did not think many patients are thinking about what happens to their data; they are more concerned with how that data is used to help improve their conditions. Davis echoed those sentiments, saying that many DBS patients have heard for years that they were not trying hard enough to get better and that somehow their
issues must be their fault, so they are just happy to get solid evidence that something is not working properly in their brains. However, both Widge and Davis agreed that consent is needed before beginning to collect patient information.
In response to an audience question, “Why is there a push for implantable psychiatric therapies [and] invasive surgeries that are costly and risky if outcomes are so ambiguous?” Davis said she does not agree that the outcomes are ambiguous. DBS for OCD has a 60–70 percent success rate, for instance, which is remarkable, she said, because these are patients who have not responded to any other standard treatments.
Widge agreed that the results are not ambiguous but said that patients who hear about, say, a 66 percent success rate still wonder what will happen to them. “Can you guarantee I won’t be one of the 33 percent who has a suboptimal outcome?” A success rate of two out of every three is good, he said, but it will likely need to be better if DBS is to become the standard of care.
Financial Considerations for Deep Brain Stimulation Uptake
Ben Greenberg asked, given the problems with insurance that speakers had discussed, whether a single-payer health system such as exists in the United Kingdom would help DBS become more widely used. Candelario-Mckeown answered that in the United Kingdom’s National Health Service, anyone who meets the criteria is allowed to have the surgery. However, he continued, referrals for DBS for the treatment of Parkinson’s disease have been declining even though the rate of diagnosis of Parkinson’s disease have been increasing, which means that the solution is not as simple as having a single-payer system. He said that it is important to work harder at educating patients and general practitioners about the procedure in order to increase the number of referrals. Another hurdle in the United Kingdom is that the National Health Service guidance specifies that a group can open a DBS service only if it includes a DBS nurse, neurologist, surgeon, psychiatrist, psychologist, and speech therapist, so only larger groups can perform DBS services.
John Krystal, the Robert L. McNeil Jr. Professor of Translational Research and a professor of psychiatry, neuroscience, and psychology at Yale University, asked how a DBS program in psychiatry can be grown and sustained, given that it is not always possible to get the procedures covered and the practice tends to lose money even when the procedures are covered and reimbursed. While the situations can vary geographically, Widge answered that his OCD program at the University of Minnesota can break even or even make a little profit. “I’m not going to say this is a moneymaker that I could sustain my life doing. . . . There are ways to make
a service like this sustainable, but it requires thought,” he said. “I think it is possible but hard.”
Davis expanded on that answer, stating that DBS is not necessarily money-losing, particularly once the implant is positioned: “We get reimbursed more for the programming codes than therapy codes.” However, getting patients to qualify for the DBS surgery requires a great deal of effort. In some cases, for instance, her clinic spent more than a year on negotiating with the insurance company and on appeals, which require much time and effort from the clinicians. “Not just anyone can battle with the insurance companies,” she said. “That is not a sustainable option for ongoing use of DBS.”
Managing Patient Expectations
Tim Denison pointed out a contradiction in expectations between DBS and pharmaceuticals. Once a DBS device is implanted, he said, it is often expected simply to work without further adjustment. By contrast, people understand that doctors may have to spend significant time getting to the proper dose of a medication. “Why [do] you think there is a different perception?” Denison asked, and what might be done to help people understand that adjustments need to be made with DBS as well?
“I think it is all about education,” Perides said. “I would say the majority of my patients know it is going to take a long time. Often, we see in pediatrics and dystonia it could take up to 2 years to find the sweet spot,” and sometimes they never find it.
Wang agreed with Denison’s observation. “Patients have this expectation of high risk, high reward, in some aspects. They think if you go through the evaluation and being a candidate, once you turn on the electricity, they sort of expect symptoms to go away.” Part of it may be because patients have seen success stories on social media where the device is turned on and the tremor goes away, she said, and doctors themselves may be partly to blame. “When I counsel patients, I show the best case [of] what this device can do. So they kind of have that built into their mind that once they turn on the device it would help a good majority of symptoms.” She is also careful to tell each patient multiple times that getting the optimal setting may take months, even as long as a year, but it is human nature to hope for the best.
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