Ethical Issues in Vagus Nerve Stimulation and Deep Brain Stimulation

This issue of Focus discusses several new and exciting techniques that fall under the broad umbrella of interventional psychiatry, a growing subspeciality that encompasses treatments ranging from frequently utilized Food and Drug Administration (FDA)-approved interventions (e.g., electroconvulsive therapy [ECT]) to off-label treatments, such as ketamine infusion therapy (1). Two interventional psychiatric treatments that fall somewhere in the middle of this spectrum are subjects of articles in this issue: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). The FDA approved VNS as an adjunctive therapy for severe treatment-refractory unipolar and bipolar depression in 2005 (2) and approved DBS under a Humanitarian Device Exemption for chronic, severe, treatment-refractory obsessive-compulsive disorder (OCD) in 2009 (3). Although both of these treatments have now been available for over a decade, they remain in very limited use. Therefore, practicing psychiatrists may lack substantial experience with these interventions. In considering the ethical implications of the use—or lack of use—of these interventions, two important issues merit particular consideration.

First, unlike other FDA-approved treatments, most psychiatrists are not intimately familiar with VNS and DBS. Given this reality, when is it appropriate for a psychiatrist to refer a patient for consideration of a treatment with which they have little experience? What should guide such a decision? Is there additional information that should be disclosed to ensure that patients are providing informed consent?

Second, unlike other psychiatric interventions such as pharmacotherapy and ECT, these devices provide continuous treatment over a prolonged period. Thus, a patient with the capacity to provide informed consent may undergo VNS or DBS implantation but lose capacity at a later time while treatment is ongoing. When a patient is deemed to lack decision-making capacity and is receiving a traditional treatment, such as medication, this treatment may be held while a surrogate decision maker is identified. What should happen if such an incapacitated patient is receiving active treatment with a neuromodulatory device? Does the treating psychiatrist have an ethical obligation to stop an ongoing treatment that he or she is neither prescribing nor administering?

These questions are not merely hypothetical: Treatment-refractory depression and OCD are problems commonly faced by psychiatrists. Patients with these conditions may needlessly suffer because their treatment providers are unaware of how to access alternative treatment interventions. DBS treatment for OCD is especially underutilized. Worldwide, the prevalence of OCD may be as high as 2% (over 150 million people), but only approximately 250 patients with OCD have received DBS, despite significant evidence of efficacy in appropriately selected patients (4, 5).

The notion that a patient with one of these implanted devices might lose capacity is not only theoretical. VNS devices are implanted in patients with treatment-refractory bipolar depression for whom the recurrence of mania is always a risk. The emergence of mania during VNS therapy in patients with unipolar depression is also a known, albeit rare, phenomenon (6). Mania, especially when severe, is often accompanied by psychosis and changes in cognition that can affect decision-making capacity. Like anyone else, patients with implanted devices may develop delirium during an acute illness, be involved in an accident that results in brain damage, or suffer a sudden stroke. Such situations may result in loss of decision-making capacity, raising ethics concerns for their psychiatric treatment providers.

The purpose of this commentary is to outline ethical challenges that psychiatrists may encounter when providing care to patients who have been treated with, or should be considered for treatment with, neuromodulatory devices. We also describe how treating psychiatrists can use a principles-based approach to navigate these situations with their patients. As described by Beauchamps and Childress (7), the four guiding principles that should guide ethical reasoning are as follows: autonomy (the obligation to respect the ability of competent individuals to make their own decisions); beneficence (the obligation to provide benefits while weighing benefits against risks); nonmaleficence (the obligation to do no harm); and justice (the obligation to be fair in distributing benefits and risks) (8).

These principles are not hierarchical (9). When a clinician is faced with a novel situation in which the right thing to do is unclear, each principle must be considered independently and weighed according to the facts of a given case.

Case 1, Part 1

Mr. Steven Johnson is a 49-year-old man who was first diagnosed as having depression at age 25. He experienced a series of depressive episodes over the following decades that typically lasted from 6 months to 2 years. The episodes were generally characterized by low mood, anhedonia, poor energy, psychomotor slowing, and insomnia. During several episodes, he experienced suicidal thoughts and was hospitalized four times. At first, medications were helpful but, as he grew older, Mr. Johnson’s depressive episodes became increasingly resistant to treatment. Eventually, numerous antidepressant medication trials were unsuccessful, including several selective serotonin reuptake inhibitors (SSRIs), venlafaxine, bupropion, nortriptyline, and tranylcypromine. Although Mr. Johnson’s father suffered from unipolar depression, no member of Mr. Johnson’s family had ever experienced a manic episode, and he himself had never experienced any symptoms of activation during his many treatments. Courses of ECT, transcranial magnetic stimulation (TMS) therapy, ketamine infusion therapy, and cognitive-behavioral therapy (CBT) all demonstrated only modest initial benefit, which quickly waned over time. Over the previous 3 years, all attempted treatments failed to adequately treat what had become the longest depressive episode of Mr. Johnson’s life. For the previous 2 years, his symptoms prevented him from continuing his work as an advertising executive at a large firm.

Mr. Johnson’s long-time psychiatrist decides to refer him for an evaluation by a psychiatrist with experience managing VNS systems. During the consultation, Mr. Johnson asks, “So is this FDA approved, like all the medications I’ve tried before?”

1.1 If the consulting psychiatrist simply replied, “Yes,” to this question without further explanation, which of the following ethical principles would be violated?

1. Respect for persons (or autonomy)

2. Beneficence

3. Nonmaleficence

4. Justice

Case 1, Part 2

After carefully discussing the procedure, including the risks, the benefits, and the range of possible outcomes and alternatives, Mr. Johnson elects to undergo VNS implantation while continuing sertraline at a dose of 200 mg daily, which had provided some modest benefit. He tolerates the surgery and several stimulation (charge) adjustments. His mood moderately improves over the ensuing 6 months. However, 8 months after surgery, Mr. Johnson suddenly begins sleeping only three to four hours per night but is not tired during the day. He becomes argumentative with his wife and tells her that he is planning to leave his advertising firm to start a new venture as a real estate developer. He begins pacing the halls of his apartment and speaking loudly, prompting his wife to bring him to the hospital, where he is admitted and diagnosed as having a manic episode.

1.2 If Mr. Johnson states that he will not allow any adjustments to his VNS device but will accept other medications, which of the following would be the most appropriate course and why?

1. Turn off Mr. Johnson’s VNS device, regardless of his wishes

2. Treat Mr. Johnson with an antimanic agent, but only if he agrees to turn off the VNS device.

3. Treat Mr. Johnson with an antimanic agent, regardless of whether he agrees to turn off the VNS device.

4. Any of the choices above are equally ethical as long as the treating psychiatrist has considered each option carefully.

Case 1, Part 3

The inpatient psychiatrist consults with Mr. Johnson’s outpatient psychiatrist and, after their discussion, recommends starting lithium, to which Mr. Johnson agrees. His manic symptoms resolve over three weeks, allowing for his safe discharge from the hospital.

Case 2, Part 1

Ms. Sarah Jordan is a 25-year-old woman with OCD. Over the course of her adolescence, she began engaging in a series of checking behaviors and washing rituals that progressively consumed more and more of her time and energy. Symptoms during her teenage years included repeatedly adjusting the positioning of objects in the family home for up to an hour at a time and washing her hands extensively after touching anything with a remote possibility of contamination, such as door handles or drawers. Her hands were frequently raw from her excessive washing, and on several occasions, she required dermatologic evaluations for skin breakdown. She became increasingly reclusive to her family home and was unable to enroll in college because of her symptoms. She was diagnosed as having OCD at the age of 16 and began treatment, initially with psychotherapy but subsequently with pharmacotherapy, which provided only modest benefit. Trials included two SSRIs with doses incrementally increased to above the typical therapeutic range and plasma blood-level monitoring to confirm adherence and rule out rapid metabolism. A several-month trial of high-dose clomipramine did not significantly reduce her symptoms. Augmentation with aripiprazole and use of novel agents—including memantine, lamotrigine, riluzole, topiramate, celecoxib, and minocycline—were all similarly ineffective, as was a trial of TMS therapy.

Ms. Jordan’s psychiatrist has never had a patient undergo DBS for OCD; has no relationships with DBS providers; and has a limited understanding of the indications, risks, and potential benefits of the procedure.

2.1 Does Ms. Jordan’s psychiatrist have an obligation to refer her for DBS evaluation? Choose the correct answer/ethical-principle pair.

1. Refer for DBS evaluation because of the ethical principles of autonomy and beneficence.

2. Do not refer for DBS because of the ethical principles of justice and nonmaleficence.

3. Refer for DBS evaluation because of the ethical principles of justice and nonmaleficence.

4. Do not refer for DBS because of the ethical principle of beneficence.

Case 2, Part 2

Ms. Jordan’s psychiatrist identifies a tertiary care center in her state with experience in DBS for OCD and brings up this possible treatment at their next session. During a wide-ranging discussion, Ms. Jordan expresses deep frustration with her symptoms, including her inability to form meaningful relationships outside of her family and her shame at not being able to pursue school and work like her siblings have. Despite her disability, she has always prided herself on doing everything she can to manage her symptoms, and she expresses some cautious interest in the DBS procedure. She also expresses some hesitancy, particularly regarding the possible financial costs, as she remains on her parents’ private insurance policy and does not know whether her parents will be able to afford out-of-pocket expenses associated with the surgery. In working through whether it might be reasonable to proceed with a DBS evaluation, Ms. Jordan’s psychiatrist decides to use the “four-topics method,” a widely used approach to ethical-clinical decision making in which the following four issues are reviewed in a deliberate manner: medical indications, preferences of patients, quality-of-life considerations, and contextual features (10).

2.2 Consideration of which of the “four topics” might argue against proceeding with the procedure, given the aforementioned information?

1. Medical indications

2. Preferences of patient

3. Patient quality-of-life considerations

4. Contextual features

Case 2, Part 3

After their discussion, Ms. Jordan decides to go ahead with a DBS treatment evaluation. At a medical center that performs DBS surgery for OCD, Ms. Jordan undergoes psychiatric evaluation and neuropsychological testing to determine whether she is experiencing undertreated anxiety or depression unrelated to OCD and to assess for neurocognitive deficits that would place Ms. Jordan at a higher risk for cognitive impairment postoperatively. Psychiatry, neuropsychology, and neurosurgery subsequently determine at a case conference that Ms. Jordan is a good candidate for the procedure. Her insurance agrees to cover the treatment, and the surgery is performed in two stages. Over the subsequent several months, settings are adjusted every few weeks. Six months after the DBS device has been implanted, Ms. Jordan’s OCD symptoms as measured by standard assessment have decreased by 50%. At first, she expresses satisfaction with the treatment outcome, begins to slowly engage with people outside of her family, and considers enrolling in classes at a nearby college. However, she subsequently expresses distress at the process of acclimating to a new identity as a person who is not chronically severely ill. She complains of feeling unprepared and lacking in the social skills necessary to live her life to the fullest because of lost time during her years of incapacity. Ms. Jordan’s psychiatrist has long believed that objective measures of symptom burden are foundational to the practice of psychiatry. Because Ms. Jordan is doing well on such assessments, her psychiatrist’s initial instinct is that Ms. Jordan’s complaints will be transient and do not require further intervention.

2.3 At this stage of treatment, which of the “four topics” of ethical decision making and associated questions are most pertinent to consider? (Choose all that apply.)

1. Medical indications—What are the goals of treatment?

2. Preferences of patient—Is the patient mentally capable and legally competent, or is there evidence of incapacity?

3. Patient quality-of-life considerations—Are there biases that might prejudice the provider’s evaluation of the patient’s quality of life?

4. Contextual features—Are there professional or business interests that might create conflicts of interest in the clinical treatment?

Case 2, Part 4

After further reflection, Ms. Jordan’s psychiatrist refers her back to the psychiatrist who had been part of the DBS multidisciplinary team for additional consultation. The DBS psychiatrist discusses with Ms. Jordan her difficulties and normalizes her experience by educating her on the fact that many patients who experience rapid improvement in symptoms after DBS can develop difficulties adapting to their new life. The majority of these reports come from patients who have undergone DBS for Parkinson’s disease (11). The DBS psychiatrist agrees to meet with Ms. Jordan on an intermittent basis to provide ongoing support and psychoeducation, while Ms. Jordan continues to see her primary psychiatrist on a regular basis. The DBS psychiatrist also recommends that Ms. Jordan undergo CBT with an emphasis on exposure and response prevention because of recent research that has indicated that this treatment can be helpful after successful DBS device implantation (12). Ms. Jordan elects to engage in CBT again, and over the following 12 months, her distress declines and her life satisfaction improves. She continues to express satisfaction with her DBS treatment.

Answers

1. The answer is A. Informed consent falls under the umbrella of the ethical principle of respect for autonomy. Although VNS was granted FDA approval, this approval was largely based on a long-term efficacy trial, not two double-blind placebo-controlled trials as is typically required for the approval of medications. The FDA approval for VNS was due in part to the fact that the treatment is a medical device, not a drug, and to the fact that the data suggest that benefits accrue over many months, making double-blind trials unethical and impractical (13).

2. The answer is C. The obligation to respect the patient’s wishes (respect for persons) to not adjust his VNS device must be weighed against what is most likely to help the patient (beneficence) as well as the obligation to “do no harm” (nonmaleficence) (14). In this situation, published data on appropriate pharmacotherapy for patients with implanted VNS devices as well as the effects of turning off a VNS device during a manic episode are limited. One case report described a patient who developed mania 6 months after VNS implantation; symptoms resolved with standard antimanic agents and without adjustments to the VNS device (15). A second case report described two patients who developed manic symptoms 8 and 9 months after implantation. In one case, mania resolved with the initiation of antimanic agents without adjustment of VNS parameters, whereas in the other, the VNS device was turned off in addition to medication changes (6). A third report described a patient who developed a manic episode 9 months after VNS stimulation and had the device turned off during hospitalization. The device was turned back on without inducing additional manic symptoms 1 month after the resolution of the manic episode (16). The largest registry studies published to date have not documented the rate of the emergence of mania during VNS treatment (17, 18). Given these data, we would argue that respecting the patient’s autonomy and the principle of beneficence—represented here by treating the patient’s mania with an antimanic agent—would outweigh the ethical principle of nonmaleficence as represented by only treating the patient if the VNS device can be turned off (A and B). D is incorrect, as all options do not have equal merit.

3. The answer is A. Respect for patient autonomy requires the physician to provide the patient with the information about DBS necessary to make a decision based on reasonable deliberation, whereas beneficence requires providing the patient with the opportunity to explore a treatment from which they may benefit. B is worthy of consideration, as one could argue that distributive justice and a fair distribution of scarce resources might argue against an expensive treatment such as DBS. However, distributive justice also calls for providing health care resources in proportion to need (19), and in this case, the need is great. Furthermore, recent studies have indicated that DBS for OCD is a cost-effective intervention compared with treatment as usual (20, 21). Finally, a psychiatrist without experience with DBS is unlikely to have enough knowledge of the treatment and its risks and benefits to rely on the principle of justice to justify declining to consult with more knowledgeable colleagues. For these reasons, B is incorrect. C is incorrect because the decision to refer the patient would not be supported by the principle of nonmaleficence. D is incorrect because the principle of beneficence would support a referral.

4. The answer is D. Contextual features fall under the ethical principles of justice and fairness and include a variety of factors that must be considered when attempting to make ethical clinical decisions. Examples of contextual features include: Are there financial conflicts of interest that touch on treatment decisions? Problems of allocation of resources? Legal issues? In the United States, resource allocation can be a major barrier to DBS treatment for OCD, as some private insurance companies have resisted approving this intervention in well-selected patients (22).

5. The answer is A and C. At this stage, the goal of treatment warrants reassessment as do possible biases of the evaluating psychiatrist. Although Ms. Jordan has demonstrated significant OCD improvement, she is now complaining of symptoms that are harder to quantify but are causing her clinically significant distress. A psychiatrist who is focused on more easily quantifiable symptoms risks failing to address what is most important to the patient. A phenomenon known as the “burden of normality” can arise when patients shift from chronic disability to improved function, as has occurred in this vignette. Although this phenomenon has been observed in at least one case of DBS treatment for OCD (23), it has been documented more extensively in patients treated with temporal lobectomy for refractory epilepsy and DBS for Parkinson’s disease. The “burden of normality” can include changes in self-perception, feelings of strangeness, a subjective sense of a loss of vitality, and challenges that lead to restructured family dynamics (24). Choice B is incorrect as there is no evidence of clinical incapacity. D is not especially pertinent in this case. There is no indication that the psychiatrist stands to gain financially from this treatment, as the psychiatrist is not responsible for administering it. The psychiatrist has no known relationships with DBS providers (see 2.1), but it is incorrect here, as these issues are not obviously implicated in this case.