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Revising the Ethical Framework for Deep Brain Stimulation for Treatment-Resistant Depression

By Somnath Das


Somnath Das recently graduated from Emory University where he majored in Neuroscience and Chemistry. He will be attending medical school at Thomas Jefferson University starting in the Fall of 2017. Studying Neuroethics has allowed him to combine his love for neuroscience, his interest in medicine, and his wish to help others into a multidisciplinary, rewarding practice of scholarship which to this day enriches how he views both developing neurotechnologies and the world around him. 


Despite the prevalence of therapeutics for treating depression, approximately 20% of patients fail to respond to multiple treatments such as antidepressants, cognitive-behavioral therapy, and electroconvulsive therapy (Fava, 2003). Zeroing on an effective treatment of “Treatment-Resistant Depression” (TRD) has been the focus of physicians and scientists. Dr. Helen Mayberg’s groundbreaking paper on Deep Brain Stimulation (DBS) demonstrates that electrical modulation an area of the brain called subgenual cingulate resulted in a “sustained remission of depression in four of six (TRD) patients” These patients experienced feelings that were described as “lifting a void,” or “a sudden calmness.” (Mayberg et al. 2005). The importance of this treatment lies in the fact participants who received DBS for TRD (DBS-TRD) often have no other treatment avenues, and thus Mayberg’s findings paved the way for DBS to have great treatment potential for severely disabling depression. 



Image courtesy of Wikimedia Commons
Because DBS involves the implantation of electrodes into the brain, Dr. Mayberg and other DBS researchers faced intense scrutiny following publication of their initial findings regarding the ethics of using what to some seems like a dramatic intervention for TRD. A number of ethical concerns surrounding DBS for depression rely on the principles of beneficence, nonmaleficence, and respect for patient autonomy (Schermer, 2011). Beneficence and nonmaleficence focus on, respectively, how much benefit and how much harm do these therapies confer to the patient (Farah, 2015). In the context of depression, these parameters can often discuss, for example, perceived threats to identity weight against benefits of mood changes. An additional issue is the hype surrounding the treatment could give patients false expectations for therapeutic outcomes (Schermer, 2011). Empirical studies have found therapeutic misconception, or the conflation of research and therapeutic intents by participants of clinical trials, to be critical area of further investigation for DBS-TRD researchers (Fisher et al. 2012). 


While these ethical criteria are important for evaluating a biomedical treatment outcome, the analysis is a strong framework for patients suffering from a strictly biological disease with a strictly biological treatment, and a poor framework for patients suffering from a disability experience. Despite the fact that the multiple correlative biomedical agents of depression do include factors such as genes, cortisol levels, and hippocampal volume, there is a critical need to assess how illness narratives reflect patient assessments of their disease, values on identity, and therapy prognosis. By adopting a social model medicine that places emphasis on the experience of illness through personal stories, “Narrative Medicine” confers increased dignity and autonomy to patients with few therapeutic choices by addressing the social consequences of disability such as stigmatization and lack of accommodation (Garden, 2010). Additionally, this framework allows for the reframing of beneficence and maleficence, focusing instead on qualitative improvements or changes over time as opposed to quantitative evaluative measures. 

People can experience depression differently even with

the same biological factors.

Image courtesy of Wikimedia Commons.

Previous literature has demonstrated, at least partly, the need to rigorously evaluate narrative beliefs of depressed patients prior to a therapeutic decision being made. Depression narratives can also give insight as to how a patient’s cognitive interpretation of their disorder effects their treatment-related behavior (Brown et al. 2001). A study by Karasz, Sacajiu, & Garcia in 2003 found that patient beliefs about the cause of their depression could be grouped into biosocial, psychosocial, psychological, situational, and somatic narratives, and subsequent studies found that the type of illness narratives a patient ascribes to predicts preferred treatment options (Khalsa et al. 2011). Other studies were conducted to assess how patient illness conception and treatment preference affects therapeutic outcome. While some studies document no relation (Dunlop et al. 2012), others document a significant interactive effect (Kocsis et al. 2009). Taking previous literature into account, DBS-TRD patient narratives and shared perspectives captured through qualitative interviews could hold critical sources of evaluative data that can help researchers determine whether the treatment is effective for TRD from a holistic perspective. 


Qualitative and narrative studies can also help researchers understand the beneficial impact of DBS on patient livelihoods. A recent study by Lipsman, Zener, & Bernstein (2013) found that when considering identity changes due to removal of brain tumors, patients often considered the ability to carry out their own livelihoods as more important than the possibility of permanent personality changes. A qualitative 2016 study by Hariz, Limousin, and Hamberg found that for patients receiving DBS to treat Parkinson’s Disease, the perceived benefit of having less invasive, more predictable tremor conferred tolerance to adverse events. The importance of the participants personal accounts was that it allowed researchers to understand the social and relational side effects, both positive and adverse, that was conferred to patient livelihoods due to implantation. For example, the study’s participants described having less dependence on family members, and others described not wishing to return to careers post-implantation due to the fear that stress may cause relapse of tremors. 


Experts believe narrative accounts, not just objective measures,

are necessary in ethical interventions.

Image courtesy of Wikimedia Commons.

That being said, the perspective of implanted patients with mood disorders remains poorly characterized. To address this issue, Klein et al. (2016) interviewed patients who underwent implantation for OCD and MDD to analyze a hypothetical situation concerning “closed-loop” DBS devices. These devices allow for the patient to exhibit an increased locus of control on their DBS therapy. Their study found four common themes that patients either strongly agreed or disagreed upon: control over device function, authentic self, relationship effects, and meaningful consent. Patients especially disagreed on how control over the device would impact their livelihoods. Klein et al. therefore demonstrates the complexity by which DBS impacts the lives of the mentally disabled, and how these patients process their disability post-implantation. While clinical data remains important in evaluating how DBS affects the clinical presentation of TRD, qualitative data demonstrates how neurotechnologies fundamentally alter the social and relational aspects of disability. 


A Neuroethics framework with further emphasis on qualitative data can provide DBS-TRD researchers a distinct perspective for analyzing developing neurotechnology that takes into account both the interests of clinical medicine and the social factors modulating a person’s treatment experience. In the context of DBS for TRD, it is important to longitudinally assess disability shifts via patient narratives such that researchers can holistically understand both the benefits and side effects of life-changing neurosurgery on patient disability experiences. Thus, qualitative data consisting of personal accounts of disease and intervention can be used to further explore how neurotechnologies impact patients with a richer analysis of patient experience more holistically than quantitative scales. 



References



Brown, C., Dunbar-Jacob, J., Palenchar, D. R., Kelleher, K. J., Bruehlman, R. D., Sereika, S., & Thase, M. E. (2001). Primary care patients’ personal illness models for depression: a preliminary investigation. Fam Pract, 18(3), 314-320.



Dunlop, B. W., Kelley, M. E., Mletzko, T. C., Velasquez, C. M., Craighead, W. E., & Mayberg, H. S. (2012). Depression Beliefs, Treatment Preference, and Outcomes in a Randomized Trial for Major Depressive Disorder. Journal of Psychiatric Research, 46(3), 375-381. doi:10.1016/j.jpsychires.2011.11.003



El-Hai, J. (2011). Narratives of DBS. AJOB Neuroscience, 2(1), 1-2. doi:10.1080/21507740.2011.547421



Farah, M. J. (2015). An ethics toolbox for neurotechnology. Neuron, 86(1), 34-37. doi:10.1016/j.neuron.2015.03.038



Fava, M. (2003). Diagnosis and definition of treatment-resistant depression. Biol. Psychiatry 53, 649-659



Fisher, C. E., Dunn, L. B., Christopher, P. P., Holtzheimer, P. E., Leykin, Y., Mayberg, H. S., . . . Appelbaum, P. S. (2012). The ethics of research on deep brain stimulation for depression: decisional capacity and therapeutic misconception. Ann N Y Acad Sci, 1265, 69-79. doi:10.1111/j.1749-6632.2012.06596.x



Garden, R. (2010). Disability and narrative: new directions for medicine and the medical humanities. Medical Humanities.



Hariz, G. M., Limousin, P., & Hamberg, K. “DBS means everything – for some time”. Patients’ Perspectives on Daily Life with Deep Brain Stimulation for Parkinson’s Disease. J Parkinsons Dis, 6(2), 335-347. doi:10.3233/jpd-160799



Karasz, A., Sacajiu, G., & Garcia, N. (2003). Conceptual Models of Psychological Distress Among Low-income Patients in an Inner-city Primary Care Clinic. J Gen Intern Med, 18(6), 475-477. doi:10.1046/j.1525-1497.2003.20636.x



Khalsa, S. R., McCarthy, K. S., Sharpless, B. A., Barrett, M. S., & Barber, J. P. (2011). Beliefs about the causes of depression and treatment preferences. J Clin Psychol, 67(6), 539-549. doi:10.1002/jclp.20785



Klein, E., Goering, S., Gagne, J., Shea, C. V., Franklin, R., Zorowitz, S., . . . Widge, A. S. (2016). Brain-computer interface-based control of closed-loop brain stimulation: attitudes and ethical considerations. Brain-Computer Interfaces, 3(3), 140-148. doi:10.1080/2326263X.2016.1207497



Kocsis, J. H., Leon, A. C., Markowitz, J. C., Manber, R., Arnow, B., Klein, D. N., & Thase, M. E. (2009). Patient preference as a moderator of outcome for chronic forms of major depressive disorder treated with nefazodone, cognitive behavioral analysis system of psychotherapy, or their combination. J Clin Psychiatry, 70(3), 354-361.



Lipsman, N., Zener, R., & Bernstein, M. (2009). Personal identity, enhancement and neurosurgery: a qualitative study in applied neuroethics. Bioethics, 23(6), 375-383. doi:10.1111/j.1467-8519.2009.01729.x



Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., . . . Kennedy, S. H. (2005). Deep brain stimulation for treatment-resistant depression. Neuron, 45(5), 651-660. doi:10.1016/j.neuron.2005.02.014



Schermer, M. (2011). Ethical Issues in Deep Brain Stimulation. Front Integr Neurosci, 5. doi:10.3389/fnint.2011.00017


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Das, S. (2017). Revising the Ethical Framework for Deep Brain Stimulation for Treatment-Resistant Depression. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2017/07/revising-ethical-framework-for-deep.html


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  1. Unknown August 24, 2017 at 6:58 PM

    The author is commended for highlighting the value of more holistic evaluations and the need for rigorous evaluation of ethical concerns when treating patients with severely refractory major depressive disorder. Such patients may have difficulty providing informed consent in light of MDD's impacts on their ability to evaluate potential harms.

    While the author recognizes the promising research and results reported by Dr. Mayberg's team, the article neglects to mention some significant facts — such as the small patient populations, the open-label nature of the research, and unresolved issues of increased suicidality and unanticipated adverse effects from the DBS.

    More importantly is the failure to mention that subsequent industry-sponsored, large-scale, randomized, double-blind clinical trials have been unable to produce similar results and in fact, were prematurely terminated in light of their inability to survive the FDA futility analysis.

    In order to prevent patients from harboring therapeutic misconception, great effort must be made to fully and objectively disclose risks and potential benefits, clearly and in plain English. Not buried in some large block of mind-numbing, carefully worded boilerplate that downplays the significance and duration of the risks.

    The author's desire to promote and ensure proper application of ethical criteria are a welcome voice in this area of research. I wish him great success.

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