OCD patients with comorbidities respond well to deep brain stimulation

by CU Anschutz Medical Campus

Repetitive hand-washing is a common OCD symptom. Credit: Lars Klintwall Malmqvist/public domain

A new study published in Frontiers in Psychiatry finds that patients with Obsessive Compulsive Disorder (OCD) as well as other psychiatric comorbidities, such as autism spectrum or tic disorders, may respond well to Deep Brain Stimulation (DBS).

07 april 2021--DBS is a minimally invasive neurosurgical procedure that uses coordinates to target certain areas of the brain, implanting electrodes that can help regulate abnormal brain activity. DBS procedures are rare for OCD in the United States; only a couple hundred patients have received this treatment for OCD management since its FDA approval in 2009 via a Humanitarian Device Exemption. The effectiveness of DBS for OCD has been well-documented in literature, but the interplay with comorbid disorders has not been as thoroughly explored.

"This study helps us understand more about real-world use of DBS for OCD," says Rachel Davis, MD, associate professor in the CU Department of Psychiatry and study principal investigator. "Most patients seeking treatment don't only have OCD, comorbidities are more the rule than the exception. So it's important to understand how this life-changing procedure can benefit our more typical patients."

Davis and clinicians at the University of Colorado Anschutz Medical Campus retrospectively examined five patients seeking DBS for OCD between 2015 and 2019. Patients exhibited comorbidities including substance use disorder, eating disorder, autism spectrum disorder, major depression, ADHD, and tic disorder. Three patients were awake during DBS surgery, allowing clinicians to check for response to stimulation (improved mood, increased energy, and reduction in anxiety), an additional way to confirm correct electrode placement. After surgery, Davis assessed response and determined the correct settings by asking patients about changes in mood, energy, and anxiety. Improvement in these areas tend to be associated with reduction in OCD symptoms later on. Change over time was monitored with a variety of IRB-approved questionnaires, gauging changes in mood, anxiety, depression and other quality of life elements affected by OCD.

Overall, these patients experienced significant improvement in OCD and mood symptoms. A standard scale for assessing symptom severity and treatment response in OCD, the Yale-Brown Obsessive-Compulsive Scale (YBOCS), measures degree of distress and impairment caused by obsessions and compulsions. A good clinical response is considered to be greater than a 35% reduction. In this study, patients averaged a 44% reduction on this scale; four out of five experienced full response with the fifth having a partial response, with approximately 25% reduction in OCD symptoms. Patients also reported an average of 53% reduction in depression symptoms.

"For these treatment-refractory OCD patients, our Psychiatric DBS program, led by Dr. Davis, is finally providing relief," says John Thompson, Ph.D., associate professor of neurosurgery at the University of Colorado School of Medicine and one of the co-authors on this manuscript. "While DBS for OCD is rare, this study is a glimpse at its potential. There is much yet to be learned about the complex interplay between circuit modulation and co-morbid symptom management in OCD patients treated with DBS."

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More information: Lora Kahn et al, Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval, Frontiers in Psychiatry (2021). DOI: 10.3389/fpsyt.2021.568932

Provided by CU Anschutz Medical Campus

Effects of deep brain stimulation in patients with Parkinson's disease

The implantation of DBS electrodes enables researchers to gain insights into the functional roles of both the basal ganglia and their associated nerve tracts (structures and nerve tracts inside the orange circle). Basal ganglia are areas of the brain that are involved in movement and motor control. Credit: Neumann/Charit

Researchers at Universitätsmedizin Berlin have studied motor and cognitive effects of deep brain stimulation in patients with Parkinson's disease. Their results show that the adverse cognitive effects of deep brain stimulation are linked to a different neural pathway than that responsible for the treatment's desired motor effects. This finding will help optimize treatments for patients with Parkinson's disease. Results from this research have been published in Brain.

04 sept 2018--Deep brain stimulation (DBS) is an effective treatment alternative for Parkinson's disease patients with an inadequate response to drug treatments. DBS targets the subthalamic nucleus, which forms part of the diencephalon, a division of the forebrain. The subthalamic nucleus integrates information from different neurons and is primarily responsible for motor processes, but also plays an important role in cognitive processes, such as decision-making and response modulation.
Researchers from Charité's Department of Neurology on Campus Charité Mitte have studied the effect of DBS on both cognitive and motor pathways. By combining behavioral experiments with brain mapping and computational modeling, the researchers were able to show that effects on motor function—such as improvements in motor control—are mediated by different neural pathways to those responsible for unwanted cognitive effects, such as premature actions in situations involving a decision-making process.
These findings enhance our understanding of the neuronal networks affected by Parkinson's disease, deliver insights into the pathophysiology of Parkinson's disease, and enable us to draw conclusions regarding the mechanism of action of DBS. "Only an improved understanding of the treatment's mechanism of action will allow us to make deep brain stimulation more effective, thus enabling us to improve the quality of life of patients with Parkinson's disease through a reduction in the side effects of treatment," explains the study's first author, Dr. Wolf-Julian Neumann, a researcher at the Department of Neurology.
As a next step, the researchers from the Movement Disorders Working Group are hoping to use measurements of neural activity to differentiate between disease-specific patterns of neural activity and patterns found in healthy individuals. "This will allow us to adapt brain stimulation treatments according to the needs of the individual patient and in real time. "It is an important step on the way to developing an intelligent, personalized and demand-adapted treatment," says Working Group Leader Prof. Dr. Andrea A. Kühn of the Department of Neurology.

More information: Wolf-Julian Neumann et al, Functional segregation of basal ganglia pathways in Parkinson's disease, Brain (2018). DOI: 10.1093/brain/awy206


Provided by Charité - Universitätsmedizin Berlin

DBS treatment may slow the progression of Parkinson's tremor in early-stage patients

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

Deep brain stimulation (DBS) may slow the progression of tremor for early-stage Parkinson's disease patients, according to a Vanderbilt University Medical Center study released in the June 29 online issue of Neurology, the medical journal of the American Academy of Neurology.

11 july 2018--The study is the first evidence of a treatment that slows the progression of one of the cardinal features of Parkinson's, but a larger-scale clinical trial across multiple investigational centers is needed to confirm the finding.
"The finding concerning tremor progression is truly exceptional," said senior author David Charles, MD, professor and vice-chairman of Neurology. "It suggests that DBS applied in early-stage Parkinson's disease may slow the progression of tremor, which is remarkable because there are no treatments for Parkinson's that have been proven to slow the progression of any element of the disease."
Patients in the Vanderbilt study were randomized to receive DBS plus drug therapy or drug therapy alone; the drug therapy alone group was seven times more likely to develop new rest tremor after two years in comparison to the DBS plus drug therapy group.
The trial, which began in 2006, was controversial because it recruited patients with early-stage Parkinson's disease for DBS brain surgery. At that time, DBS was approved for only advanced-stage Parkinson's disease when symptoms were no longer adequately controlled by medication.
"Since this was the first early DBS trial, it was unknown whether there were individual motor symptoms very early in Parkinson's disease that may be more potently improved by DBS," said lead author Mallory Hacker, Ph.D., research assistant professor of Neurology.
The post hoc analysis showed that 86 percent of the drug therapy patients developed rest tremor in previously unaffected limbs over the course of the two-year period, while that occurred in only 46 percent of patients who had received DBS therapy in addition to drug therapy. Four of the DBS patients had rest tremor improvement and rest tremor completely disappeared from all affected limbs for one DBS patient.
The FDA has approved Vanderbilt to lead a large-scale, Phase III multicenter study that will enroll 280 people with very early-stage Parkinson's disease, beginning in 2019, and 17 other U.S. medical centers have joined the DBS in Early Stage Parkinson's Disease Study Group to participate.
"The field of DBS therapy for Parkinson's disease is moving toward earlier stages of treatment, therefore, we must conduct the pivotal trial to ensure patient safety and provide the Parkinson's community with the best possible medical evidence to guide treatment," Charles said.


Provided by Vanderbilt University Medical Center

Deep brain stimulation showing promise for patients with mild Alzheimer's disease over 65

Dr. Andres Lozano of Krembil Neuroscience Centre at Toronto Western says 'we are encouraged by these findings.' Credit: The Globe and Mail

An age group analysis of data from the ADvance trial has shown that participants over the age of 65 continue to derive the most benefit from Deep Brain Stimulation of the fornix (DBS-f), as observed in the data from the phase 2 findings (12—24 months) of the Phase II trial.

22 jun 2018--The findings, published today in the Journal of Alzheimer's Disease, by a team of researchers led by Dr. Andres Lozano at Toronto Western Hospital's (TW) Krembil Neuroscience Centre (KNC), are the potential beginnings of a patient profile for DBS-f treatment for Alzheimer's disease. The neurology and psychology aspects of the trial in Toronto were led by TW neurologist Dr. Peter Tang-wai and neuropsychologist Dr. Mary-Pat McAndrews respectively.
To further explore the benefits for this demographic, the research team is soon launching a Phase III, multi-centre international trial that will study the effects of DBS-f in 140 patients over age 65.
"We are encouraged by these findings as they continue to help us identify who will benefit most from DBS to treat Alzheimer's disease and learn more about this illness," says Dr. Andres Lozano, neurosurgeon and the principal investigator of the study. "With so few treatments available and the incidence of Alzheimer's only expected to increase, we really need to fully explore all treatments that seem to be of benefit to patients."
These latest results were captured from the second year of data of the ADvance trial whose first-year data was published in 2016. In that trial, forty-two patients with mild Alzheimer's disease were enrolled in a randomized, double-blind multicentre phase II clinical trial and implanted with DBS electrodes directed at the fornix—a bundle of nerve fibres in the brain that carry signals from the hippocampus—and followed for a total of two years.
In the first 12 months of the trial, to better measure the impact of electrical stimulation in the brain, patients were randomly assigned to either the "on" or "off" stimulation group after their procedure and monitored. Once this phase of follow up was complete, all patients then had their electrodes turned on, and were followed for another 12 months.
In the second 12-month phase, researchers noted similar observations they had seen in the first phase: that, although there were no differences overall in cognitive outcomes between study participants who had their device turned on right after surgery and those who had it turned on after 12 months, those 65 years of age and older appeared to experience a slower progression of Alzheimer's than those under that age, regardless of when their device was turned on.
"The next phase of our research will help determine whether this observed benefit is something we continue to see in this age group," says Lozano who is also University Professor and Chairman, Department of Neurosurgery, University of Toronto. "If it does, this could potentially give us a treatment for mild, late-onset Alzheimer's disease."


Provided by University Health Network

Deep brain stimulation effects may last for 10 years in patients with Parkinson's disease

One decade after receiving implants that stimulate areas of their brains, patients with Parkinson's disease (PD) appear to sustain improvement in motor function, although part of the initial benefit wore off mainly because of progressive loss of benefit in other functions, according to a report published Online First by Archives of Neurology, one of the JAMA/Archives journals.

10 aug 2011--According to background information in the article, several previous clinical studies have shown deep brain stimulation of the subthalamic nucleus (STN-DBS) for PD to be effective and safe. Studies have shown that the technique, which stimulates a part of the brain involved in motor function, may have advantages compared with other medical treatments in terms of controlling motor complications and improving quality of life. "The motor improvement induced by STN stimulation has been reported to be sustained for up to five to eight years after surgery, although part of the initial benefit progressively deteriorates, mainly because of worsening axial signs," write the authors. "To date, studies with postoperative follow-up for longer than eight years are lacking."

Anna Castrioto, M.D., from the Università degli Studi di Perugia, Perugia, Italy, and colleagues conducted a study of 18 patients with advanced PD who had received DBS implants for PD between 1996 and 2000. Motor assessments were conducted before implantation and at one, five and 10 years. All motor assessments were videotaped. Patients were assessed without medication, without stimulation, without either, and with both. At each assessment, the researchers recorded every patient's medications and dosages.

At 10 years, the combination of medication and STN-DBS was associated with significantly better motor, resting and action tremor, bradykinesia (slowed movement) and rigidity scores. Compared with baseline, reductions were also seen in the scores in the medication and no medication conditions, the dyskinesia (difficulty controlling movement) and motor fluctuation scores and the levadopa-equivalent daily dose. However, axial signs (such as posture, gait and balance) showed the most progressive decline in stimulation and medication response.

"Our findings further support the long-term response to STN stimulation in patients with advanced PD, showing a prolonged motor improvement up to 10 years," conclude the authors.

More information: Arch Neurol. August 8, 2011. doi:10.1001/archneurol.2011.18

Provided by JAMA and Archives Journals

Consensus reached on use of Parkinson's treatment

Since the late 1990s, deep brain stimulation (DBS) has proven to be a lifeline for some patients suffering from Parkinson's disease, a cruel neurological disorder that can cause lack of control over movement, poor balance and coordination, and rigidity, among other symptoms.

14 oct 2010--The procedure is used only for patients whose symptoms cannot be adequately controlled with medications. A neurosurgeon uses magnetic resonance imaging or computed tomography to identify the exact target within the brain where abnormal electrical nerve signals generate the disease's tremors and other symptoms, and a neurostimulator is then surgically implanted to deliver electrical stimulation to that area to block the signals.

The goal, ultimately, is to improve the patient's quality of life.

Yet despite its effectiveness, there has been no consensus on several aspects of the use DBS, including which patients make the best candidates, where the optimal location for the placement of electrodes is, and the role that still exists for surgical removal of the damaged areas of the brain.

To address these concerns, a more than 50 DBS experts — including world-renowned neurologists, clinicians and surgeons — pooled their experience with the procedure and reached a consensus. The goal of this "meeting of the minds" was to better inform Parkinson's patients and their families about the potential of DBS treatment and to better inform the medical community in suggesting the procedure.

The results of their April 2009 meeting are presented in the current online edition of the journal Archives of Neurology.

"We know that very little accessible information is out there to help a Parkinson's patient make an informed decision as to whether he or she would be a good candidate for deep brain stimulation," said Jeff Bronstein, a UCLA professor of neurology and lead author of the report.

Surgical trials take a long time, he said, and what information is available on DBS appears in academic journals, is focused and limited, and is usually written by one group reflecting their biases.

Bronstein, who directs the UCLA Movement Disorder Program and is a member of the UCLA Brain Research Institute, said the results of the group's meeting will help clarify some of the issues about DBS treatment. Among their findings:

• The best candidates for DBS are those who can't tolerate the side effects of medications, who don't suffer from significant active cognitive or psychiatric problems, and who do suffer from tremors and/or motor fluctuations.


• DBS surgery is best performed by an experienced team and neurosurgeon with expertise in stereotactic neurosurgery — microsurgery deep within the brain that is based on a three-dimensional coordinate system using advanced neuroimaging.


• DBS, when used in the two most commonly treated areas of the brain — the subthalamic nuclei and the globus pallidus pars interna — is effective in addressing the motor symptoms of Parkinson's, but treatment in the subthalamic nuclei may cause increased depression and other symptoms in some patients.


• Surgical removal of the area of the brain causing Parkinson's disease is still an effective alternative and should be considered in patients.


• Surgical complication rates vary widely, with infection being the most commonly reported complication of DBS.

Multiple authors were involved in the report; Bronstein, the lead author, reports no conflict of interest.

Deep Brain Stimulation Shows Promise for Patients With Alzheimer's

08 aug 2010— In a world first, Dr. Andres M. Lozano and his team at Toronto Western Hospital has shown using Deep Brain Stimulation (DBS) on patients with early signs of Alzheimer's disease is safe and may help improve memory.

The phase one safety trial of six Ontario patients took place from 2005 to 2008. All patients left hospital within 2 to 3 days of surgery, and continue to participate in regular follow-up cognitive assessments.

Throughout these assessments, Dr. Lozano says half the patients continue to perform better than predicted -- that is -- their memory capacity has improved, or deteriorated less than expected.

"While the study was not looking for efficacy, the results suggest that of the six patients, three may have done better than if the Alzheimer's disease was allowed to run its course," commented Lozano. "We showed that not only is this a safe procedure, but that the evidence is there to warrant a bigger trial. Any amount of time that extends quality of life and quality years to someone with Alzheimer's may be a benefit."

Dr. Lozano first discovered the potential for DBS to treat Alzheimer's disease while treating a patient for obesity using DBS back in 2003. While signaling areas of the brain, Dr. Lozano and his team triggered memories in the patient. In follow-up testing the patient's memory improved and Dr. Lozano set in motion the first ever DBS trial of patients with early signs of Alzheimer's disease.

"We've demonstrated this is safe, and that the evidence warrants more study. We're now planning a phase two, multi-centred trial -- we're just waiting on the funding," says Dr. Lozano.

Results of Dr. Lozano's trial are published in the August 4 issue of Annals of Neurology.

Deep Brain Stimulation Helps Those With Advanced Parkinson's

By Amanda Gardner
08 jan 2009 -- The largest study of its kind finds that deep brain stimulation improves both physical function and quality of life after six months in patients with Parkinson's disease.

Deep brain stimulation (DBS) performed better than currently available drug treatments, but it did carry some risks, including one death, according to a study in the Jan. 7 issue of the Journal of the American Medical Association.

"This basically corroborates what has largely emerged over the last decade from literature and clinical experience showing pretty dramatically the potential benefit of DBS for Parkinson's," said Dr. Fred Marshall, medical director of the deep brain stimulation program at the University of Rochester Medical Center, in New York.

Despite abundant clinical experience, there have been few controlled trials on the topic, added colleague Dr. Irene Richard, an associate professor of neurology and psychiatry at the University of Rochester Medical Center. "This is corroborative, that surgery is helpful, but it is associated with more risk."

Deep brain stimulation, approved for Parkinson's by the U.S. Food and Drug Administration in 2002, is relatively widely used in patients with advanced Parkinson's who are no longer being helped by drugs.

"First-line medication works quite well for some window of time, occasionally one's whole life, but typically, a patient takes more and more medications more often. Their life is ruled by medication to maintain a decent function," said study co-author Dr. William J. Marks Jr., an associate professor of neurology at the University of California, San Francisco, and director of the San Francisco VA Parkinson's Disease Research, Education & Clinical Center.

Marks has served as a consultant to Medtronic, the manufacturer of the DBS device, as have other members of the study team. The trial was funded by the VA, the U.S. National Institute of Neurological Disorders and Stroke, and Medtronic.

As Parkinson's advances, motor symptoms are often accompanied by anxiety, depression and other non-motor symptoms.

Generally, DBS, a procedure which involves placing a thin wire that can carry electrical currents deep within the brain, is performed after patients are already failing on their medications.

For this study, 255 Parkinson's patients were randomized to receive either DBS or "best medical therapy." One-quarter of the participants were 70 or older, a population underrepresented in previous trials.

DBS was targeted either to the subthalamic nucleus (same as current practice) or to the globus pallidus; results of that comparison are forthcoming.

After six months, participants in the DBS arm gained about 4.6 hours per day of "on time," meaning time without troubling movement problems, compared with no gain for patients on best medical therapy.

Seventy-one percent of DBS patients, and only 32 percent of patients in the control group, experienced "clinically meaningful motor function improvements." Those receiving DBS also reported improvements in quality of life.

However, at least one serious adverse event occurred in 49 of the DBS patients vs. 15 in the other group.

Those receiving DBS also experienced small problems with cognitive functioning similar to patterns seen in previous studies and had more falls resulting in fractures and other injuries.

Although both younger and older patients gleaned similar benefits from DBS, older patients were more prone to adverse effects.

This "landmark" study, said Marks, "proved superior for such patients, rather than a tweak-and-adjustment [of medications] approach."

Hopefully, he added, the findings will encourage more neurologists to consider DBS for appropriate patients.

"I think this is going to spur those people who have still been on the fence about DBS to feel comfortable with it," Marshall said.

"This study, to me, confirms the tremendous usefulness of the procedure in spite of the warning, of course, that there were certain adverse effects," said Dr. Carlos Singer, director of the Parkinson's Disease Center and a professor of neurology at the University of Miami Miller School of Medicine. "It means that we have to continue refining our selection of patients. You don't want to be overzealous in picking up patients . . . take into account that the surgery was not effective for everybody."

More information

Visit the U.S. National Institute of Neurological Disorders and Stroke for more on Parkinson's disease.

Promising results in deep brain stimulation for patients with treatment-resistant depression

22 july 2008--New data from a study of patients with treatment-resistant depression who underwent deep brain stimulation (DBS) in the subcallosal cingulate region (SCG or Cg25) of the brain shows that this intervention is generally safe and provides significant improvement in patients as early as one month after treatment. The patients also experienced continued and sustained improvement over time.
The data are reported in the online issue of Biological Psychiatry by scientists from the University of Toronto and Emory University School of Medicine.
The study began at the University of Toronto in 2002, led by Helen S. Mayberg, MD, and collaborators Andres Lozano, MD, PhD, neurosurgeon, and psychiatrist Sidney Kennedy, MD.
Mayberg is now a professor in the Department of Psychiatry and Behavioral Sciences and the Department of Neurology at Emory University School of Medicine. This clinical trial is the culmination of Mayberg's 20 years of research using brain imaging technology that has worked to characterize functional brain abnormalities in major depression and to identify the mechanisms of various antidepressant treatments.
A report on the first six patients in the study was published in the Journal Neuron in 2005. The new paper reports on an expanded sample of patients and an extended period of clinical follow-up.
DBS uses high-frequency electrical stimulation targeted to the specific areas of the brain involved in neuropsychiatric disease. Twenty patients received SCG DBS for 12 months. Twelve of 20 patients experienced a significant decrease in depressive symptoms (defined by a 50 percent decrease in the Hamilton Depression rating scale) by six months, with seven patients essentially well with few remaining symptoms (remission, defined as a Hamilton Depression Rating Scale score <8). Benefits were largely maintained at 12 months with continued stimulation. No long-term side effects were reported.
Each study patient was implanted with two thin wire electrodes (one on each side of the brain) in the white matter adjacent to SCG. The other end of each wire was connected under the skin of the neck to a pulse generator implanted in the chest – similar to a pacemaker – that directs the electrical current. The researchers regulated the intensity of the current according to the response of the patient. Only patients who were unable to get better with most other types of antidepressant treatment – including medication, psychotherapy and electroconvulsive therapy – were included in the study.
"In previous studies using brain imaging, we found the subcallosal cingulate region was a key region in an emerging emotion regulation circuit implicated in major depression," explains Mayberg.
"We postulated that if stimulation worked for the treatment of other neurological disorders where abnormal function of specific circuits was well established, such as Parkinson's disease, then stimulation of the Cg25 region within this apparent depression circuit might provide significant benefit for patients with treatment-resistant depression."
The researchers were able to track the clinical response of the patients over a 12-month period using standard depression rating scales as well as various quantitative measures of behavior and general functioning, neuropsychological testing and scanning of both regional brain blood flow and glucose metabolism using positron emission tomography (PET).
PET imaging of these patients demonstrated that metabolic activity changed locally at the site of stimulation but also throughout the previously identified depression network, providing evidence that modulating the circuit and not just a single region was likely responsible for the antidepressant effects.
"We see depression as a complex disturbance of the specific circuits in the brain responsible for regulating mood and emotions," Mayberg says. "We hypothesized that if DBS could locally modulate a critical central location within this mood circuit, such modulation would result in clinical improvement – and it appears it does."
Mayberg initiated an expanded version of her Toronto study at Emory in 2007 with psychiatrist Paul Holtzheimer, MD, and neurosurgeon Robert Gross, MD, PhD, and with grant support from the Woodruff Fund, The Stanley Medical Research Institute and the Dana Foundation.
The new Emory clinical trial is tackling a number of unanswered issues including the testing of patients with bipolar II depression and refinement of the targeting and selection of the electrodes using new imaging techniques. The Emory study will enroll 20 patients and will be conducted over a period of at least three years.
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The Toronto study was funded in part by a Distinguished Investigator Award from National Alliance for Research in Schizophrenia and Depression (HSM).
Reference: Biological Psychiatry published online July 2008 DOI: 10.1016/jbiopsych.2008.05.034
Dr. Mayberg is an inventor on patents covering the technology discussed in this article. Dr. Mayberg is also a paid consultant for ANS, which has licensed the technologies. Dr. Holzheimer is also a paid consultant for ANS. These relationships have been reviewed and approved by Emory University in compliance with its policies on conflicts of interest.

APA: Deep Brain Stimulation Lifts Depression in Multicenter Trial

By Michael Smith
WASHINGTON, 06 may 2008-- Deep brain stimulation relieved depression in 56% of patients treated in a multicenter Canadian trial.
Six months after the treatment, nine of 16 patients had at least a 40% improvement on the Hamilton Rating Scale for Depression, according to Sidney Kennedy, M.D., of the University Health Network in Toronto.
The "findings are robust," Dr. Kennedy said at the annual meeting of the American Psychiatric Association, adding that they should be followed up with a double-blind randomized trial.
The study follows the technique used in a pilot study three years ago, led by Helen Mayberg, M.D., of Emory University, but uses a different device, Dr. Kennedy said.
That earlier study sparked an outburst of interest in the idea of stimulating brain areas as a possible therapy for major depression. Dr. Mayberg discussed the technique with MedPage Today in an exclusive interview. Dr. Mayberg and colleagues have since expanded their initial study to 20 patients and a paper detailing their results is in press, she said, but she was reluctant to give details until the paper is published.
The 20-patient study reported by Dr. Kennedy was intended to show that the results obtained by the Toronto group could be reproduced by doctors elsewhere. (Dr. Mayberg was consulted on its design but was not otherwise involved, she said.)
"We wanted to show it wasn't just a Toronto effect," Dr. Kennedy said.
The method involves inserting electrodes into the subgenual cingulate cortex Brodmann Area 25, which is part of a brain circuit thought to be disregulated in depressed patients.
Because the treatment has only been used a few dozen times -- one estimate says about 50 cases worldwide -- the patients selected are usually highly refractory to treatment, Dr. Kennedy said.
In his study, volunteers had to have documented resistance to at least four types of treatment, including cognitive behavioral therapy. They also had to be in a depressive episode at least two years long and have a score on the Hamilton scale of 20 or higher.
The researchers treated five cases in Vancouver, six in Montreal, and nine in Toronto, but several patients had not yet reached the six-month landmark when the poster was prepared, Dr. Kennedy said.
When the researchers considered the latest follow-up, rather than the six-month mark, 15 of 19 (or 79%) had at least a 40% improvement on the Hamilton scale, he said. (The 20th patient was not included because the implant was too recent.)
The results are "exciting," said Thomas Insel, M.D., director of the National Institute of Mental Health, and the whole approach "could be tremendously informative" about which brain circuits are involved in depression.
"What you really want to know," Dr. Insel said, "is how these interventions affect the circuitry."
"I think we're going to get closer to that with (deep brain stimulation) than with pharmacotherapy," he added.
One of the next steps is to combine the intervention with neuroimaging to pin down exactly which brain regions are involved in depression and how they interact to cause the disease.
"I think that's where this will have to go," Dr. Insel said.