Written by Sarah Low

Edited by Oh Sher Li

On the 10th of February 2017, we held our first Seminar Session, in the style of a friendly debate and discussion, on the topic of Deep Brain Stimulation, namely:

Should Deep Brain Stimulation (DBS) be used as the main treatment option for neurological diseases?

Deep Brain Stimulation, also known as DBS, is a surgical procedure during which a neurostimulator is implanted (also known as a ‘pacemaker for the brain’) into the area just under the collarbone. Electrodes extending from the neurostimulator are then placed at specific areas of the brain (known as DBS targets). When stimulated, the electrodes affect the corresponding nerve signals directly, and so may reverse the symptoms of the patient. The intensity of the electrical pulse is adjustable, and as such, any stimulation-induced side effects are reversible. While DBS is invasive in that surgery is required, DBS does not damage the brain tissue in any way.

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Source: NorthJersey.com

DBS is currently used to treat movement disorders, such as Parkinson’s Disease, Dystonia (uncontrollable muscle spasms), and Essential Tremor (uncontrollable shaking), however, there is ongoing research on its applicability to psychiatric disorders, particularly Depression (usually Major Depressive Disorder (MDD)), and Obsessive-Compulsive Disorder (OCD), among others. Generally, DBS is used to treat patients who have not responded well to pre-existing treatment for their disorder (ie: refractory), and are fit to undergo surgery – simply put, DBS is currently used as a last resort, often kept within the safety-net of a clinical trial – especially for psychiatric disorders, for which DBS use is still largely experimental.

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Source: Vancouver Sun

Thus, we decided to discuss if DBS should, in fact, be the last resort – or perhaps a treatment option introduced to the patient at the outset.

In brief, both sides (those for DBS as the main treatment option, and those against) agreed on the potential of DBS as a transformative treatment. Advocates for DBS as the main treatment option focused on how DBS could save the lives of patients left with no viable alternative (particularly, refractory patients with extreme symptoms). On the other hand, those against DBS as the main treatment option stood their ground on how the uncertainty of the extent of risks to the patient and dubious success rates for different disorders would run counter to the core tenet of non-maleficence to the patient in medical practice.

It was an intriguing and thought-provoking 2 hours of spontaneity!

We’re certainly looking forward to seeing our members again in the upcoming session on mirror neurons!

Argument Summaries:

For Deep Brain Stimulation as a main treatment option for neurological disorders:

Position:

  • We believe that Deep Brain Stimulation should be considered as the main treatment option for neurological disorders, specifically for patients who are both eligible for and have been evaluated to benefit from DBS.
  • We define the main treatment option as one that should be introduced and explained to the patient when treatment options are first being discussed, and while the risks should be highlighted, DBS should not be framed as a last resort, regardless of the patient’s final decision.
S/N Argument Evidence Source
1 DBS is especially critical as a main treatment option (and not a last resort) for patients with no viable alternatives “Medication is commonly effective, but 20–30 % of patients are refractory to medical therapy.” This indicates there is a significant proportion of patients for whom DBS would be a potentially viable mode of treatment. Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484
2 DBS is able to treat certain symptoms that other medications cannot alleviate, and in so doing can cater to patients’ specific needs “Among neuromodulation therapies, DBS offers the attractive potential to modulate directly the specific malfunctioning brain circuitry responsible for the manifestation of neuropsychiatric illness, as it has done with proven success in the treatment of medication-refractory movement disorders.” Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484
3 Side effects are reversible and changes in treatment to counter the side effects can be administered within a short period of time because the side effects can be observed almost immediately; on the other hand this is not necessarily true for side effects of medication and/or therapy “Stimulation-induced side effects such as mood changes are temporary and adjustable.” Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484
“Adverse effects arising directly from stimulation itself are common and strongly linked to the neuroanatomical site of stimulation… Stimulation-induced side effects are frequently transient and rapidly reversible with adjustment or cessation of stimulation.” Fitzgerald, P. & Segrave, R. (2015). Deep brain stimulation in mental health: Review of evidence for clinical efficacy. Australian & New Zealand Journal of Psychiatry. 49 (11) : 979 – 993.
4 Localised nature of the DBS treatment may be more effective for some patients, as compared to the general nature of medication
5 While the actual mechanism of DBS is unknown, the success rates demonstrated in clinical studies suggest good prospects for DBS to be integrated into clinical practice beyond that of treatment of movement disorders “Overall, the published response rate to DBS therapy, defined as the percentage of patients with > 50 % improvement on the Hamilton Depression Rating Scale, is reported to be 40–70 %, and outcomes were comparable across studies.” Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484
Implantation of “the DBS electrodes bilaterally in lateral habenulae … resulted in a remission of depression symptoms after 60 weeks of stimulation”.
“An overlapping series of clinical trials has been conducted evaluating the efficacy of DBS applied to the SAC (Subgenual anterior cingulate) … 20 patients [were] followed for 12 months (Lozano et al., 2008) or greater than 3 years (Kennedy et al., 2011). Remission rates of 33% at 12 months and 43% at 3 years or last follow-up (up to 6 years) were reported. The most recent report … also documented improvements in physical health and social functioning and found that work participation rates had increased from 10% of patient’s pre-DBS to 65% at 6 years post-implantation (Kennedy et al., 2011).” Fitzgerald, P. & Segrave, R. (2015). Deep brain stimulation in mental health: Review of evidence for clinical efficacy. Australian & New Zealand Journal of Psychiatry. 49 (11) : 979 – 993.
“Data from a number of these studies were combined in a report in 2010 which describe the outcomes of a total of 26 patients … and followed for between 3 and 36months (Greenberg et al., 2010). The overall response rate was 62%. In addition to a reduction in OCD severity, there was a substantial global reduction in severity of depression and generalised anxiety.”
6 Cost of DBS (a one-time surgery, along with trips to the hospital every few years for monitoring and changing of batteries) far outweighs the costs of lifelong medication (notwithstanding the progression of the disease, which would require additional medication)
7 The risks of DBS should not be ignored, however, instead of letting the risks overshadow the potential of DBS, treatment and ethics guidelines can be put in place to ensure non-maleficence to the patient. Certain risks of DBS (such as death by suicide, particularly in patients suffering from major depressive disorder) are due to the nature of the illness (MDD), rather than the DBS treatment itself. It remains imperative that measures be put in place to address the risks as best as possible, however, it is not possible for any treatment to have zero risk entirely.
“Completed suicide and suicide attempts were the most significant adverse events following DBS surgery and happened both with and without stimulation. Several studies excluded patients with suicidal ideation in the hope of avoiding this adverse event, but given the high incidence of suicide in patients with refractory depression, it is unlikely that this complication could be completely avoided even with such exclusion criteria. All patients included in these studies had severe, treatment-refractory depression and were at higher risk of suicide owing to the nature and severity of their illness.” Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484

Against Deep Brain Stimulation as a main treatment option for neurological diseases:

Position:

  • We believe that Deep Brain Stimulation should not be considered a main treatment option for neurological disorders at the present, however, it remains an exciting future prospect.
S/N Argument Evidence Source
1 DBS is still in an experimental stage and its efficacy is still not well-understood; there have been no studies that compare psychotherapy and DBS in the long-term, and thus their efficacy and remission rates have not been compared – insufficient clinical evidence for DBS to be used beyond the realm of clinical trials “No class I evidence exists in the literature supporting the efficacy of DBS for major depressive disorder (MDD), and the optimal DBS target for treatment-resistant depression remains unclear. DBS for MDD should, therefore, be considered experimental at present.” Morishita, T. et al. (2014). Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes. Neurotherapeutics. 11 : 475 – 484
“Dr. Darin Dougherty and his colleagues report the results of the first large-scale, randomised, sham- controlled trial of deep brain stimulation treatment for treatment-resistant symptoms of depression. Thirty patients received active DBS or sham ‘placebo’ stimulation for 16 weeks… A two-year open-label continuation phase followed. This study, conducted at five medical centers across the U.S. that collaborated on the project, failed to find that DBS reduced depression symptoms better than sham stimulation.” Krystal, J. (15 August 2015). National Study of Deep Brain Stimulation for Depression Fails to Demonstrate Efficacy. Biological Psychiatry (Elsevier Press Release)
“Successful targeting of 6 brain sites for depression has been reported, but little is known regarding the biomarkers that predict better outcomes for each patient.” Mi K. (2016) Use of deep brain stimulation for major affective disorders (Review). Experimental and Therapeutic Medicine. 12 : 2371 – 2376.
2 Variability between probability of success between patients
3 Side effects are not well-documented (unlike current medication and therapy) and remain uncharacterisable and thus unpredictable, so the potential for negative risk factors is high (as compared to medication and other mainstream measures) Trial-and-error’ style of treatment implies that the patient could be at risk of complications due to a lack of understanding of the mechanism of DBS. “Adverse effects arising directly from stimulation itself are common and strongly linked to the neuroanatomical site of stimulation. They most often occur at contacts and stimulation parameters that are not optimal for therapeutic benefit and are elicited during the ‘trial-and-error’ style search for optimal stimulation settings.” Fitzgerald, P. & Segrave, R. (2015). Deep brain stimulation in mental health: Review of evidence for clinical efficacy. Australian & New Zealand Journal of Psychiatry. 49 (11) : 979 – 993.
4 Side effects of DBS can adversely affect the patient’s quality of life Surgical risks of DBS include: Bleeding of the brain that can lead to permanent deficit (8%), Stroke or other permanent neurological deficits (8%), Infection (15%), Haemorrhage (5%), Seizure (2%), and Death (1.1%). Other risks include, “the potential for air to enter the brain, and leakage of cerebrospinal fluid or brain fluid”, and “‘Hardware-related’ complications are also possible (including breakage or migration of the implant’s wires or electrodes), all of which could necessitate additional brain or chest surgeries, including device wire fractures that make it impossible for the pacemaker to deliver electricity to the contacts in the brain”. Egan, D. (September 2015). Adverse Effects: The Perils of Deep Brain Stimulation for Depression. Mad in America.
“different target sites in the brain do require different DBS implantation trajectories and it is possible that higher rates of haemorrhage could result from implantation sites in less accessible brain regions, for example, where there are a greater number of blood vessels in the immediate region.” Fitzgerald, P. & Segrave, R. (2015). Deep brain stimulation in mental health: Review of evidence for clinical efficacy. Australian & New Zealand Journal of Psychiatry. 49 (11) : 979 – 993.
5 High maintenance of the neurostimulator (regular check-ups required to monitor the condition and change batteries) “Higher stimulation voltages showed a correlation with a better clinical outcome (26), and are associated with higher battery use, leading to more frequent replacement of batteries and possible surgical complications. “ Mi K. (2016) Use of deep brain stimulation for major affective disorders (Review). Experimental and Therapeutic Medicine. 12 : 2371 – 2376.
6 DBS is not suitable for everyone, particularly the children and elderly
7 DBS may affect the long-term brain development of young patients (especially children)
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