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Beyond Blind Optimism and Unfounded Fears: Deep Brain Stimulation for Treatment Resistant Depression

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Abstract

The introduction of new medical treatments based on invasive technologies has often been surrounded by both hopes and fears. Hope, since a new intervention can create new opportunities either in terms of providing a cure for the disease or impairment at hand; or as alleviation of symptoms. Fear, since an invasive treatment involving implanting a medical device can result in unknown complications such as hardware failure and undesirable medical consequences. However, hopes and fears may also arise due to the cultural embeddedness of technology, where a therapy due to ethical, social, political and religious concerns could be perceived as either a blessing or a threat. While Deep Brain Stimulation (DBS) for treatment resistant depression (TRD) is still in its cradle, it is important to be proactive and try to scrutinize both surfacing hopes and fears. Patients will not benefit if a promising treatment is banned or avoided due to unfounded fears, nor will they benefit if DBS is used without scrutinizing the arguments which call for caution. Hence blind optimism is equally troublesome. We suggest that specificity, both in terms of a detailed account of relevant scientific concerns as well as ethical considerations, could be a way to analyse expressed concerns regarding DBS for TRD. This approach is particularly fruitful when applied to hopes and fears evoked by DBS for TRD, since it can reveal if our comprehension of DBS for TRD suffer from various biases which may remain unnoticed at first glance. We suggest that such biases exist, albeit a further analysis is needed to explore this issue in full.

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Notes

  1. The approval was a humanitarian device exemption.

  2. This is one of the clinical diagnoses of depression, sometimes referred to as recurrent depressive disorder, clinical depression, major depression, and unipolar depression. Whenever “depression” is mentioned in the paper, this refers to MDD unless something else is specified.

  3. The expression “treatment-refractory depression” refers to depressions where standard therapies have failed. However, there seems to be no agreement on how many treatment strategies that are necessary, neither regarding for instance the number of antidepressant drugs used, nor whether electroconvulsive therapy is mandatory, before the depression is considered to be treatment-refractory; an important constraint to keep in mind when the expression is employed. Further, though both unipolar and bipolar depressions can be treatment-refractory, it is the former that is presupposed throughout the text.

  4. General claims about depression require some caution: The etiology of depression is debated as is whether it is a disease, a disorder or, as has been claimed by for instance the anti-psychiatry movement, a social construct; neither is the neurobiological mechanisms fully understood, and there have been suggestions that depression may in fact be more than one disease considering variance in symptoms, response to therapy, comorbidities etc.; the diagnosis is based on assessment tests performed by the patient and physician, allowing for individual variances as well as for instance cultural differences; it has been estimated that a substantial share of those suffering from depression never get spotted since they refrain from seeking health care etc. The following section should be read with these limitations kept in mind.

  5. Though these results are ambiguous; it is still not clear whether it is the depression that causes the brain damage or vice versa, alternatively there could be an unknown factor causing both the depression and the cell death. This ambiguity also applies to other examples of cell death throughout the text.

  6. Even in a country as Sweden, with a population of only nine million people, the economic burden of depression, including both direct and indirect costs, is high and keeps increasing. In 1997 the cost of depression was €1.7 billion, while in 2005 it had increased to €3.5 billion.

  7. The quote obtained from Stone 2001.

  8. Response was defined as a 50% reduction in the 17 item Hamilton Rating Scale for Depression (HRSD-17) score from the pre-treatment baseline, whereas remission was defined as a HDRS-17 score of 7 or less. Both measures were made after a 6 month follow-up period.

  9. From the 1950s onward experiments were conducted where rudimentary electrodes stimulated the brain to treat psychiatric disorders, such as the Tulane Electrical Brain Stimulation Program, conducted by Robert Heath, and the experiments conducted by José Delgado at Yale University. However, since these early experiments do not live up to the standard of todays rigorous research protocols, they are not listed in the main text.

  10. The six patients from Mayberg’s study were included in this study. Response and remission were defined as stated in the previously mentioned study.

  11. Response was defined as a 50% reduction in the Hamilton Depression Rating Scale (HDRS28) score from the pre-treatment baseline, whereas remission was defined as a HDRS28 score of less than 10.

  12. To make this comparison more comprehensive, some features are mentioned which strictly speaking are concerns of nonmaleficence.

  13. Vagus nerve stimulation got a Food and Drug Administration approval for TRD in 2005.

  14. The number of procedures are somewhat deceptive since the limbic leucotomy is nothing but a combination of the cingulotomy and the stereotactic subcaudate tractotomy.

  15. Though these enhancements, if real and not due to other explanations such an inadequate assessing tools, are side effect of the stimulation such anecdotal reports have opened up for the question if DBS in the future could, and will, be used not only for treatment but for augmenting the function of normally functioning brains.

  16. For instance, is the patient really treatment-refractor?

  17. A proposed hypothesis is that the electrical stimulation inhibits the effected structures neuronal activity, while another—more recent—suggestion is that the reduction of disease symptoms is due to a disruption of the transmission of pathologic bursting and oscillatory activity created by a change in the stimulated nucleus’s firing pattern. The nucleus firing pattern adapts to the DBS pulse train, thus creating a more regular bursting, which supposedly blocks the above mentioned pattern of abnormal neural activity.

  18. Such studies are now underway both in Europe and America, but we have yet to await the results.

  19. Such studies can be achieved without sham surgery even if all patients receive a neurostimulator as long as some implants are activated whilst others are not, where on and off periods is reversed during the duration of the study. With this design, neither the patient nor the evaluating physician knows which implant is activated [34]. However, it has been claimed that many patients can feel when their neurostimulators are on, hence making a double-blinded study impossible, which in turn would limit the scientific value of the results [40].

  20. This has also been pointed out by Bell et al.

  21. Safe should not be understood as that there are no risks of harm involved in ECT, there are. Temporary memory losses are common, and in rare cases these memory losses are permanent. However, ECT remains an underutilized therapy considering the vast empirical evidence supporting its employment.

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Acknowledgements

We want to thank prof. Dan Egonsson, Dr Maria Christensson and Dr Kristin Zeiler, and in addition participants of the research seminars in ethics and practical philosophy at Lund University for their helpful remarks on earlier drafts of this text. We also want to thank the two anonymous reviewers for valuable feedback. This research project was sponsored by a Linné grant, project number 60012701, from the Swedish Research Council and The Knut and Alice Wallenberg Foundation, project number: KAW 2004.0119.

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Authors and Affiliations

  1. Neuronano Research Center, Lund University, Lund, Sweden

    Veronica Johansson, Martin Garwicz, Martin Kanje, Jens Schouenborg & Ulf Görman

  2. Ethics Unit, Centre for Theology and Religious Studies, Lund University, Lund, Sweden

    Veronica Johansson, Helena Röcklinsberg & Ulf Görman

  3. Neurophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden

    Martin Garwicz & Jens Schouenborg

  4. Department of Cell and Organism Biology, Lund University, Lund, Sweden

    Martin Kanje

  5. Molecular Psychiatry Unit, Department of Clinical Sciences, Lund University, Lund, Sweden

    Anders Tingström

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Johansson, V., Garwicz, M., Kanje, M. et al. Beyond Blind Optimism and Unfounded Fears: Deep Brain Stimulation for Treatment Resistant Depression. Neuroethics 6, 457–471 (2013). https://doi.org/10.1007/s12152-011-9112-x

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