Therapeutic Neuromodulation Weblog

Brainsway gets Israeli registration in Israel for deep-brain stimulation device to treat depression

2011-10-05T04:48:00.000-07:00

Brainsway Ltd. wins Israeli Ministry of Health approval for its non-invasive deep-brain stimulation device, which uses transcranial magnetic stimulation to treat depression, bipolar disorder and schizophrenia.

Brainsway Ltd.'s transcranial magnetic stimulation device won Israeli Ministry of Health approval to treat major depression, bipolar disorder and negative impairment in schizophrenia patients.

The approval clears Jerusalem-based Brainsway to sell the non-invasive TMS device, which delivers brief magnetic pulses to the brain, to four medical centers specializing in mental disorders.

"We are very pleased to receive this vote of confidence in the Deep TMS technology from our homeland's regulatory authority. We are now working to update indications with the Israeli Ministry of Health to bring them more in line with the approvals that we've already received in Europe," CEO Uzi Sofer said in prepared remarks.

BROADEN Study on DBS for Depression by St. Jude to be expanded

2011-07-13T01:53:00.000-07:00

The FDA has allowed St. Jude to expand its BROADEN study to up to 20 study centers across the US with a total of 125 patients, the company has announced that they later request approval to further expand the study to a total of 231 patients. You nan read the press release of the company here.

10 Mental Health Conditions that Commonly Plague College Students

2011-07-11T11:57:00.001-07:00

Not that we would propose DBS for all these conditions....

Really interesting data on the prevalence of mental disorders in college kids.

Portrayal of Psychiatric DBS in the popular press

2011-07-05T00:29:00.000-07:00

An interesting piece titled Brain surgery saved my husband from the torment of depression on DBS for major depression in a patient in Oxford; read it here. This is an example of a rather carefully written article, not selling DBS as a miracle cure. The case has been published 2 years ago in J Neurosurg (PMID: 19284230).

Worthwhile reading.

Doctors push for brain surgery to treat depression

2011-03-03T00:05:00.000-08:00

An interesting development from down under:

"Deep brain stimulation has been used to treat patients with Parkinson's disease for decades, but more recently it has been trialled on patients with severe depression and some brain surgeons want the procedure to be made more widely available."

Read it here.

Synaptic potentiation onto habenula neurons in the learned helplessness model of depression

2011-02-27T23:56:00.000-08:00

This paper demonstrates that presynaptic action on neurons of the lateral habenula contribute to the learned helplessness model of depression in rodents, read it here.

Deep brain stimulation: Experts raise alarms about aggressive marketing

2011-02-16T01:17:00.000-08:00

An article in the Harvard Health Blog discussing the Health Affairs paper and its write up in the New York Times. Read it here.

Wariness on Surgery of the Mind

2011-02-15T00:39:00.000-08:00

A very balanced and thoughtful article written by Benedict Carey in the NYTimes on a paper which appeared in the February issue of Health Affairs. This paper makes some ethical arguments regarding the use of the Humanitarian Device Exemption for DBS in Obsessive-Compulsive Disorder.

Brain implants have long-lasting effect on depression

2011-02-11T01:07:00.000-08:00

Allison Abbott writes in naturenews on long-term outcomes of cg25 DBS for Major Depression, read it here.

Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans

2011-02-11T01:05:00.000-08:00

A paper which appeared in Neuroscience & Biobehavioral Reviews reports data showing that all currently researched DBS targets for depression - which all lead to comparable response rates in patient populations with comparable treatment refractoriness - actually stimulate in close proximity to the medial forebrain bundle (MFB) pointing to the possibility that this structure might be involved in mediating antidepressant effects. Full reference below.

Volker A. Coenen, Thomas E. Schlaepfer, Burkhard Maedler, Jaak Panksepp. Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans. Neuroscience & Biobehavioral Reviews, 2010; DOI: 10.1016/j.neubiorev.2010.12.009

Brain Pacemakers: A Long-Lasting Solution in the Fight Against Depression?

2011-02-11T00:53:00.000-08:00

A report on a putative new DBS target - the medial forebrain bundle - for depression, read it here. It refers to a recent paper in Neuroscience & Biobehavioral Reviews titled Cross-species affective functions of the medial forebrain bundle—Implications for the treatment of affective pain and depression in humans.

Deep brain stimulation surgery 'first' for depression

2011-01-26T02:04:00.000-08:00

This is a press release on a program which was broadcasted by the BBC January 24, 2011. They (the journalists) claim that this is the 'first' use of DBS for depression (I hope that the investigators don't). Read the release and watch the video here.

Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond

2010-12-01T01:35:00.000-08:00

PMID: 21103178

AUTHORS: John P O'Reardon, Pilar Cristancho, Andrew D Peshek

REFERENCE: Psychiatry (Edgmont) 2006 May 3(5):54-63

Neuromodulation appears to be emerging gradually as a new therapeutic
field in psychiatric treatment. It encompasses neuropsychiatric medical
devices, such as vagus nerve stimulation (VNS), transcranial magnetic
stimulation (TMS), deep brain stimulation (DBS), and electroconvulsive
therapy (ECT). As a therapeutic approach to affective disorders,
neuromodulation shifts the focus from the monoamine synapse to neural
circuitry of the brain, which is dysregulated in depression. This neural
circuitry has been elaborated on over the course of 15 years of
neuroimaging research in mood disorders and is now believed to encompass
disturbances in a frontolimbic network. These include reduced
metabolism and blood flow in the prefrontal cortex and anterior
cingulate and pathologically increased activity in the subgenual
cingulate and amygdala.VNS is an implanted device that has established
efficacy in pharmaco-resistant epilepsy. It was approved by the FDA for
the treatment of severe, recurrent unipolar and bipolar depression in
July of 2005. VNS adopts a bottom-up approach to modulating the neural
circuitry of depression by stimulating vagal afferent fibers in the neck
, which carry impulses to the brain stem to target there the locus
ceruleus and dorsal raphe nucleus. Now that VNS has moved beyond the
experimental phase and into the clinic, psychiatrists are faced with
deciding who is an appropriate patient for this surgical implant and how
to integrate VNS into existing treatment in order to optimize both
efficacy and safety.This review of VNS will assess the efficacy and
safety data that led to the FDA approval. We will also review for the
busy clinician how VNS is likely to translate into clinical practice as
a treatment option for patients in need who are suffering from severe
depression.

Modeling of electromagnetic stimulation of the human brain

2010-12-01T01:32:00.000-08:00

PMID: 21095888

AUTHORS: Dmitry Lazutkin, Peter Husar

AFFILIATION: Division of Biological Signal Processing, Department of Biomedical Engineering and Medical Informatics, Ilmenau University of Technology, PO Box 100565, 98684, Germany.

REFERENCE: Conf Proc IEEE Eng Med Biol Soc 2010 1():581-4

The World Health Organization estimates depression as a serious threat
to the health of millions of people worldwide. The purpose of this paper
is to introduce the ongoing research devoted to the investigation of a
possibility to use low-field electromagnetic stimulation of the human
brain in the treatment of depressive disorder. In the course of the work
the 3D models of transcranial magnetic stimulation and low-field
magnetic stimulation based upon the use of a layered sphere head model
have been developed. An initial approach towards the realistic human
head reconstruction has been made. The revealed order of the stimulating
electromagnetic field suitable for operation makes it possible to draft
a technical specification for the stimulation device.

Optogenetics: Controlling the Brain with Light

2010-12-01T00:29:00.000-08:00

A wonderfully written, easy to understand paper on Optogenetics, written by the expert, Karl Deisseroth Access the article here.

50 Famous & Successful People With OCD

2010-10-08T00:25:00.000-07:00

And now for something completely different .... While we think about neuromodulatory approaches to obsessive-compulsive disorder, we could forget about our patients symptoms easily. The www.nursingschools.net has compiled a referenced list of 50 famous people with OCD; something which really contributes to the destigmatization of the disorder. They write:

Here are 50 famous sufferers of OCD who've managed to control their condition and find success in Hollywood, science, music, and other fields.

Access the page here.

Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial

2010-05-19T09:27:00.000-07:00

PMID: 20439832

AUTHORS: Mark S George, Sarah H Lisanby, David Avery, William M McDonald, Valerie Durkalski, Martina Pavlicova, Berry Anderson, Ziad Nahas, Peter Bulow, Paul Zarkowski, Paul E Holtzheimer, Theresa Schwartz, Harold A Sackeim

AFFILIATION: Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA. georgem@musc.edu

REFERENCE: Arch Gen Psychiatry 2010 May 67(5):507-16

CONTEXT: Daily left prefrontal repetitive transcranial magnetic
stimulation (rTMS) has been studied as a potential treatment for
depression, but previous work had mixed outcomes and did not adequately
mask sham conditions. OBJECTIVE: To test whether daily left prefrontal
rTMS safely and effectively treats major depressive disorder. DESIGN:
Prospective, multisite, randomized, active sham-controlled (1:1
randomization), duration-adaptive design with 3 weeks of daily weekday
treatment (fixed-dose phase) followed by continued blinded treatment for
up to another 3 weeks in improvers. SETTING: Four US university
hospital clinics. PATIENTS: Approximately 860 outpatients were screened
, yielding 199 antidepressant drug-free patients with unipolar
nonpsychotic major depressive disorder. INTERVENTION: We delivered rTMS
to the left prefrontal cortex at 120% motor threshold (10 Hz, 4-second
train duration, and 26-second intertrain interval) for 37.5 minutes (
3000 pulses per session) using a figure-eight solid-core coil. Sham rTMS
used a similar coil with a metal insert blocking the magnetic field and
scalp electrodes that delivered matched somatosensory sensations. MAIN
OUTCOME MEASURE: In the intention-to-treat sample (n = 190), remission
rates were compared for the 2 treatment arms using logistic regression
and controlling for site, treatment resistance, age, and duration of the
current depressive episode. RESULTS: Patients, treaters, and raters
were effectively masked. Minimal adverse effects did not differ by
treatment arm, with an 88% retention rate (90% sham and 86% active).
Primary efficacy analysis revealed a significant effect of treatment on
the proportion of remitters (14.1% active rTMS and 5.1% sham) (P = .02
). The odds of attaining remission were 4.2 times greater with active
rTMS than with sham (95% confidence interval, 1.32-13.24). The number
needed to treat was 12. Most remitters had low antidepressant treatment
resistance. Almost 30% of patients remitted in the open-label follow-up
(30.2% originally active and 29.6% sham). CONCLUSION: Daily left
prefrontal rTMS as monotherapy produced statistically significant and
clinically meaningful antidepressant therapeutic effects greater than
sham. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00149838.

Update of the Avery-George-Holtzheimer Database of rTMS Depression Studies

2010-05-19T09:03:00.000-07:00

UPDATED as of 05/19/2010; Please direct any feedback to Paul Holtzheimer.

This database has been compiled by David Avery, M.D., Mark George, M.D. and Paul E. Holtzheimer, MD

Download the file"rTMS depression database updated 2010.xls" here.

Disruption of the right temporoparietal junction with transcranial magnetic stimulation reduces the role of beliefs in moral judgments

2010-04-16T00:53:00.000-07:00

A great article in PNAS:

When we judge an action as morally right or wrong, we rely on our capacity to infer the actor's mental states (e.g., beliefs, intentions). Here, we test the hypothesis that the right temporoparietal junction (RTPJ), an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation (TMS) to disrupt neural activity in the RTPJ transiently before moral judgment (experiment 1, offline stimulation) and during moral judgment (experiment 2, online stimulation). In both experiments, TMS to the RTPJ led participants to rely less on the actor's mental states. A particularly striking effect occurred for attempted harms (e.g., actors who intended but failed to do harm): Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms.

Electrical engineering fixes brain's circuit board

2010-04-09T02:54:00.000-07:00

An article in the NewScientist reviewing results from studies of DBS for Depression.

Editorial: Deep brain electrodes are real hope for mental illness

Deep Brain Stimulation Mechanisms in Depression

2010-04-09T02:45:00.000-07:00

An interesting analysis by way of the AL FIN Blog:

DBS involves continually delivering high-frequency pulses of weak current to a particular region via stimulators that are surgically inserted into the brain. Although invasive, it works so well for Parkinson's disease and other movement disorders that it is now mainstream, with tens of thousands of patients implanted.

In the last decade, researchers have tested DBS on a variety of other conditions. It has proved effective at reducing some symptoms of bipolar disorder and Tourette's syndrome (see table). It was recently approved by the US Food and Drug Administration to treat obsessive compulsive disorder. _NS

The effect of deep brain stimulation (DBS) on a depressed brain is turning out to be more complex than at first thought. DBS is not merely affecting the part of the brain near the electrode. DBS appears to be affecting entire circuits of brain interaction -- performing a type of fine-tuning or calibration of the circuitry.
The researchers implanted the stimulators into the subgenual area, which is involved in emotion, in six severely depressed patients for whom all other treatments had failed, including several types of antidepressant drugs and electroconvulsive therapy. Four reported vast improvements (Neuron, vol 45, p 651).

The region was selected because brain imaging studies had shown it to be hyperactive in many people with depression. Most researchers thought that DBS worked by silencing activity in that area. This would explain why so many patients responded as soon as their stimulators were switched on: many said the operating room looked brighter than when they had gone in, for example, a sign of a changed outlook on life. It was as if "something painful had suddenly stopped", Mayberg said at a recent lecture on her work at the Massachusetts Institute of Technology.

That wasn't the whole story, however. PET scans revealed that while DBS damped down activity in the subgenual area as expected, other regions appeared affected too, particularly parts of the nearby prefrontal cortex, which is involved in decision-making and evaluating emotions. "We got lucky," says Mayberg. "It worked, but probably not for the reason we thought."

...His [Thomas Schlaepfer] team used DBS on the nucleus accumbens, an area involved in assessing pleasurable stimuli that is known to behave abnormally in depression (Biological Psychiatry, DOI: 10.1016/j.biopsych.2009.09.013).

PET scans of seven of the patients revealed that the implant didn't seem to affect activity in the nucleus accumbens itself, but instead suppressed the subgenual area - also called Brodmann's area 25 - just as with Mayberg's team (see diagram). It also had reverberations in parts of the prefrontal cortex.

"There are clear connections between area 25 and the nucleus accumbens," Schlaepfer says. He suspects that the three areas are part of a brain network that his and Mayberg's teams both tapped into.

The experiments also raise the question of why DBS doesn't work in everyone. While all of Schlaepfer's patients felt their lives had improved a year after having the stimulator implanted - be it returning to work, taking up a hobby or making new friends - some fared much better than others.

...That's where Mayberg's most recent results, which she presented at the MIT lecture, come in. To see if there were any pre-existing differences in the brains of DBS responders and non-responders, which might predict who should go to the trouble of getting a DBS implant, Mayberg's team turned to functional MRI, which allows you to see which regions light up at the same time - indicating that they are "connected".

In depressed patients who went on to respond to DBS, a part of their prefrontal cortex tended to light up in conjunction with the subgenual area. This did not happen in non-responders. In these patients, the amygdala, which is involved in fear and other emotions, tended to be connected to the subgenual area - not the case in responders. _NS
One of the aims of psycho-neurologists at the Al Fin Institutes of Psycho-Neurology, is to place the diagnoses of mental disorders on a sound scientific foundation. The demonstration of physical changes in brain circuits as a result of successful treatment would go a long way toward making the treatment of mental disorders more respectable within medicine and society.

St. Jude Medical Awarded U.S. Patent For Neurostimulation Therapy For Depression

2010-02-08T02:08:00.000-08:00

St. Jude Medical, Inc. (NYSE:STJ) announced it has been awarded a patent from the U.S. Patent and Trademark Office conducive to treating depression using neurostimulation psychotherapy in an arena of the intellectual known as Brodmann Area 25.

Brodmann Close 25 is a organization within the subcollosal gyrus region of the brain. It is the focus of the St. Jude Medical BROADEN(TM) (BROdmann Neighbourhood 25 DEep brain Neuromodulation) muse about, which is evaluating whether deep sense stimulation (DBS) cure can workers people who suffer from major depressive disorder, a dire form of impression. This study is being conducted under a U.S. Scoff and Dose Administration (FDA) Investigational Device Exemption (IDE), which was announced in February 2008.

“This patent is a cornerstone in developing our passage to lost brain stimulation fitted depression, which is the leading belief of disability in the U.S. come up to b become illnesses,” said Chris Chavez, president of St. Jude Medical’s ANS Division. “The BROADEN study provides hope respecting a sober new psychotherapy to the millions of patients still seeking treatment for their critical concavity.”

On April 4, St. Jude Medical enrolled the first unfailing, a woman from Chicago, in the BROADEN study. The patient will be implanted with the Libra(R) Deep Thought Stimulation Methodology, an investigational device, at Alexian Brothers Behavioral Condition Sanatorium in Chicago.

“There is a tremendous need for inquire into in the area of major depressive disorder, distinctively among those who have weak other treatment options,” said Anthony D’Agostino, M.D., medical director of Alexian Brothers Behavioral Health Hospital and the prima donna investigator at the writing-room site. “We hope that our participation in the study inclination combine to the centre of research previously conducted for patients hardship from dent and, if possible, shed some clarification on what type of patient is most likely to benefit.”

Co-investigators at Alexian Brothers Behavioral Health Infirmary are psychiatrists Greg Teas, M.D., Slash Lerman, M.D. and neurosurgeon Konstantin Slavin, M.D.

The BROADEN inspect is a controlled, multi-install, blinded, clinical enquiry of deeply brain stimulation in the U.S. It will build upon the pioneering depression work conducted at the University of Toronto by a research team led by neurologist Helen S. Mayberg, M.D. (now with Emory University School of Medicine) and neurosurgeon Andres Lozano, M.D.

The Libra Deep Brain Stimulation System, which is being evaluated in this sanctum sanctorum, is designed to deliver mild pulses of common from a device implanted next-door the collarbone and connected to small electrical leads placed at specific targets in the brain.

In the U.S., more than 21 million adults suffer from some kind of depressive disorder, according to the National Alliance of Mental Health. Since barely approximately 80 percent can be effectively treated with currently available therapies, approaching 4 million matured Americans spend with despair that does not respond to medications, psychotherapy or electroconvulsive therapy. The World Health Organization estimates that depression affects thither 121 million people worldwide.

For more news apropos this study, call toll-free 866-787-4332 or visit http://www.BROADENstudy.com.

St. Jude Medical

Treating Depression by Stimulating the Pleasure Center

2010-02-04T00:47:00.000-08:00

Philadelphia, PA, 26 January 2010 - Even with the best of available treatments, over a third of patients with depression may not achieve a satisfactory antidepressant response. Deep brain stimulation (DBS), a form of targeted electrical stimulation in the brain via implanted electrodes, is now undergoing careful testing to determine whether it could play a role in the treatment of patients who have not sufficiently improved during more traditional forms of treatment.

A major challenge of this work is determining the best region of the brain to stimulate. Some researchers stimulate the subgenual prefrontal cortex, a brain region implicated in depressed mood states, while others stimulate a region called the “anterior limb of the internal capsule”, a nerve pathway that passes through the basal ganglia, a lower brain region. Physicians publishing a new report in Biological Psychiatry now describe findings related to the stimulation of the nucleus accumbens, a brain region the size of a hazelnut associated with reward and motivation that is implicated in processing pleasurable stimuli, sometimes referred to as the “pleasure center” of the brain. The inability to experience pleasure is a key symptom of depression and previous studies have shown that functioning of the nucleus accumbens is impaired in depressed individuals.

Bewernick and colleagues administered DBS treatment in ten patients with severe long-term depression who had not responded to multiple other antidepressant treatments, including psychotherapy, drug treatments and electroconvulsive treatment. After one year of DBS, all patients showed some improvement, and half of them experienced significant improvement in their symptoms of depression, astonishing considering they had not responded to any prior antidepressant treatment. In addition, the patients showed reduced ratings of anxiety and had only minor side effects. Importantly, none of their overall brain functioning was impaired by the DBS treatment.

“The nucleus accumbens is a brain region that animals will seek to stimulate even if they do not appear depressed and this is one reason that it is sometimes referred to as a reward center. It is interesting to note that the patients in this study did not simply feel stimulated or euphoric; instead, there appeared to be reductions in depressed mood that paralleled an increase in the capacity for pleasure,” commented Dr. John Krystal, Editor of Biological Psychiatry. “This finding will stimulate further study on the role of the nucleus accumbens in depression and its treatment.”

The authors caution that because they studied only a small number of people, further research is necessary before DBS could be considered a clinically useful treatment for treatment-resistant depression. There are also important ethical considerations, since DBS treatment first requires potentially risky brain surgery. However, these preliminary findings are promising that DBS may provide relief to individuals with severe treatment-resistant depression.

# # #

Notes to Editors:
The article is “Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression” by Bettina H. Bewernick, René Hurlemann, Andreas Matusch, Sarah Kayser, Christiane Grubert, Barbara Hadrysiewicz, Nikolai Axmacher, Matthias Lemke, Deirdre Cooper-Mahkorn, Michael X. Cohen, Holger Brockmann, Doris Lenartz, Volker Sturm, and Thomas E. Schlaepfer. At the University Hospital in Bonn, Germany, authors Bewernick, Hurlemann, Matusch, Kayser, Grubert, Hadrysiewicz, Axmacher, Cooper-Mahkorn, and Schlaepfer are affiliated with the Department of Psychiatry and Psychotherapy, with Axmacher also with the Department of Epileptology, while Brockmann is with the Department of Nuclear Medicine. Schlaepfer is also with the Departments of Psychiatry and Mental Health, Johns Hopkins University, Baltimore, Maryland. Lenartz and Sturm are affiliated with the Department of Functional Neurosurgery, University Hospital, Cologne, Germany. Cohen is from the Department of Psychology, University of California, Davis, California. Lemke is with the Department of Psychiatry, Hospital Alsterdorf, Hamburg, Germany.

The article appears in Biological Psychiatry, Volume 67, Issue 2 (January 15, 2010), published by Elsevier.

The authors’ disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at

http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological_Psychiatry_Editorial_Disclosures_08_01_09.pdf.

Full text of the article mentioned above is available upon request. Contact Maureen Hunter at m.hunter@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

Biological Psychiatry is ranked 4th out of the 101 Psychiatry titles and 14th out of 219 Neurosciences titles on the 2008 ISI Journal Citations Reports® published by Thomson Scientific.

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Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression

2010-02-04T00:40:00.000-08:00

Biological Psychiatry
Volume 67, Issue 2, 15 January 2010, Pages 110-116

Stimulating Research on the Treatment of Depression: Electroconvulsive Therapy, Transcranial Magnetic Stimulation, and Deep Brain Stimulation
doi:10.1016/j.biopsych.2009.09.013 | How to Cite or Link Using DOI
Copyright © 2010 Society of Biological Psychiatry Published by Elsevier Inc.
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Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression
Bettina H. Bewernick^a, René Hurlemann^a, Andreas Matusch^a, Sarah Kayser^a, Christiane Grubert^a, Barbara Hadrysiewicz^a, Nikolai Axmacher^a^,^d, Matthias Lemke^g, Deirdre Cooper-Mahkorn^a, Michael X. Cohen^e, Holger Brockmann^f, Doris Lenartz^c, Volker Sturm^c and Thomas E. Schlaepfer^a^,^b^,

a Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
b Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, Maryland
c Department of Functional Neurosurgery, University Hospital, Cologne, Germany
d Department of Epileptology, University Hospital, Bonn, Germany
e Department of Psychology, University of California, Davis, California
f Department of Nuclear Medicine, University Hospital, Bonn, Germany
g Department of Psychiatry, Hospital Alsterdorf, Hamburg, Germany

Received 9 July 2009; revised 3 September 2009; accepted 11 September 2009. Available online 14 November 2009.

Background
While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising.
Methods
Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (±SD) length of the current episode was 10.8 (±7.5) years; the number of past treatment courses was 20.8 (±8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (±5.3).
Results
Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [±2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala.
Conclusions
We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Key Words: Deep brain stimulation; functional neuroimaging; major depression; neuromodulation; nucleus accumbens; treatment resistance

Transcranial direct current stimulation for the treatment of depression

2010-02-04T00:31:00.000-08:00

Int J Neuropsychopharmacol. 2010;13(1):61-9.

A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression

Loo CK, Sachdev P, Martin D, Pigot M, Alonzo A, Malhi GS, Lagopoulos J, Mitchell P.

School of Psychiatry, University of New South Wales, Sydney, Australia. colleen.loo@unsw.edu.au

Two recent sham-controlled studies found that transcranial direct current stimulation (tDCS) was an effective treatment for depression. As tDCS is painless, relatively safe and inexpensive, its efficacy in treating depression warrants further investigation. This double-blind, randomized study tested tDCS at the same stimulation parameters as a previous positive study (1 mA current strength, five treatment sessions, active or sham, given on alternate days) in 40 depressed participants. Anodal stimulation was centred over the left dorsolateral prefrontal cortex, with the cathode placed on the lateral aspect of the contralateral orbit. tDCS was continued up to a total of ten active sessions per participant. Mood outcomes were measured by psychiatrist raters blind to treatment condition using the Montgomery-Asberg and other depression rating scales. Psychomotor speed was assessed immediately before and after a single tDCS session and attention, frontal executive function, working memory and verbal learning were assessed after each group of five sessions. Overall depression scores improved significantly over ten tDCS treatments, but there was no between-group difference in the five-session, sham-controlled phase. tDCS was found to be safe, with no adverse effects on neuropsychological function, and only minor side-effects. It is recommended that the efficacy of tDCS in depression be further evaluated over a longer treatment period, using enhanced stimulation parameters.

PMID: 19671217 [PubMed - in process]

Deep Brain Stimulation: Beyond Movement Disorders

2010-02-01T00:17:00.000-08:00

Deep Brain Stimulation: Beyond Movement Disorders

The 2010 Progress Report on Brain Research

By Brenda Patoine

Excellent review on DBS for psychiatric indications. Read it here.

NIMH Center to Study DBS in OCD created at the University of Rochester Medical Center

2009-10-16T01:58:00.000-07:00

Rochester will serve as the hub of a five-year collaborative effort that includes six institutions around the nation and in Puerto Rico. The Silvio O. Conte Center will link more than 50 researchers who will focus on how deep brain stimulation affects people with obsessive-compulsive disorder. Read more about it here.

Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controll

2009-10-07T02:34:00.000-07:00

PMID: 18447962
TITLE: Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis.
AUTHORS: D J L G Schutter
AFFILIATION: Experimental Psychology, Utrecht University, Utrecht, The Netherlands. d.schutter@uu.nl
REFERENCE: Psychol Med 2009 Jan 39(1):65-75
BACKGROUND: For more than a decade high-frequency repetitive
transcranial magnetic stimulation (rTMS) has been applied to the left
dorsolateral prefrontal cortex (DLPFC) in search of an alternative
treatment for depression. The aim of this study was to provide an update
on its clinical efficacy by performing a meta-analysis involving double
-blind sham-controlled studies. METHOD: A literature search was
conducted in the databases PubMed and Web of Science in the period
between January 1980 and November 2007 with the search terms 'depression
' and 'transcranial magnetic stimulation'. Thirty double-blind sham-
controlled parallel studies with 1164 patients comparing the percentage
change in depression scores from baseline to endpoint of active versus
sham treatment were included. A random effects meta-analysis was
performed to investigate the clinical efficacy of fast-frequency rTMS
over the left DLPFC in depression. RESULTS: The test for heterogeneity
was not significant (QT=30.46, p=0.39). A significant overall weighted
mean effect size, d=0.39 [95% confidence interval (CI) 0.25-0.54], for
active treatment was observed (z=6.52, p<0.0001). Medication
resistance and intensity of rTMS did not play a role in the effect size
CONCLUSIONS: These findings show that high-frequency rTMS over the
left DLPFC is superior to sham in the treatment of depression. The
effect size is robust and comparable to at least a subset of
commercially available antidepressant drug agents. Current limitations
and future prospects are discussed.

US Study Of Deep Brain Stimulation For Obsessive-Compulsive Disorder?

2009-10-07T00:44:00.000-07:00

Butler Hospital in Providence, R.I., is leading a clinical study evaluating the effectiveness and safety of deep brain stimulation (DBS) for severe obsessive-compulsive disorder (OCD). Benjamin D. Greenberg, MD, PhD, associate professor of psychiatry at Butler Hospital and the Alpert Medical School of Brown University, is the lead investigator. He noted, "In the most severe cases, OCD causes profound impairment in work and social life, as well as tremendous suffering. Our work, plus that of colleagues in Europe, shows that DBS is a promising treatment for patients with OCD who remain very ill and debilitated despite the best available standard treatments, which are cognitive behavioral therapy and medications."

In DBS, thin wires are implanted in brain circuits that are involved in OCD. The wires are connected under the skin to a battery-powered stimulating device, which is implanted in the patient's chest. These are the same kinds of devices that have become an FDA-approved standard of care for people with Parkinson's disease and other movement disorders. Pilot studies at Butler's OCD Research Clinic, Massachusetts General Hospital, and the other centers that are part of this trial have found that stimulation in this area reduced OCD symptoms.

According to the World Health Organization, OCD is one of the most disabling medical conditions. DBS offers people who have not been helped by specific behavior therapy for OCD and medications another potential treatment option.

The U.S. Food and Drug Administration has approved DBS for humanitarian use for patients with OCD. The study is working closely with other scientists and physicians who were just awarded funding by the National Institute of Mental Health to establish the Silvio O. Conte Center to carry out research to understand more about DBS in OCD. Suzanne Haber, PhD, heads this center at the University of Rochester Medical Center, and Dr. Greenberg at Butler Hospital and Brown University is its co-director.

Dr. Greenberg says that there is also a companion study of brain functioning in OCD that does not involve surgery.

Source: Butler Hospital

Pico-Tesla Starts Phase III Clinical Trial of Its Proprietary Magnetic (Magneceutical) Therapy for Parkinson`s Disease

2009-10-06T04:38:00.000-07:00

This sounds interesting, I at least never heard of this "Pico-Tesla" technology. Read the Press Release here, and a blurb about the method:

Magneceutical Therapy involves the use of an extremely low-level electromagnetic field (EMF) applied by a specially designed device-the Resonator, invented by Dr. Jerry I. Jacobson, along with proprietary therapeutic protocols-intended to improve a number of the signs and symptoms of Parkinson`s and other neurological-based diseases.

Using Deep Brain Stimulation on the Mind: Handle with Care

2009-10-01T05:42:00.000-07:00

A great article by Mahlon R. DeLong on DBS in the DANA Foundation Magazine.

The abstract:

Deep brain stimulation has worked for many patients with Parkinson’s disease and other movement disorders that have not responded to other treatments. However, its use as a therapy for psychiatric disorders, while promising, is not yet proven. Mahlon DeLong, a pioneer in the use of deep brain stimulation, explains the technique and why its use for depression, obsessive-compulsive disorder and other psychiatric problems requires extra caution.

Deep Brain Stimulation for Severe Alcoholism

2009-09-10T02:00:00.000-07:00

The Neurocritic Blog writes somewhat critically about data recently published on the use of DBS for the treatment of Alcoholism He cites a recent paper on ethical issues of dbs in psychiatry. Very interesting, read it here.

Deep Transcranial Magnetic Stimulation Gets European Regulatory Approval for Treatment of Depression

2009-09-09T00:50:00.000-07:00

Brainsway, a firm building transcranial magnetic stimulation systems (TMS) out of Jerusalem, Israel, just received European approval to market its devices for the treatment of depression. The TMS treatment is likely to be used initially for cases of severe drug resistant depression. But we can envision a day when this technology becomes a mainstream therapeutic option for bipolar disorder and some other psychiatric diseases.

About the technology from Brainsway:

Transcranial magnetic stimulation (TMS) is a noninvasive technique used to apply brief magnetic pulses to the brain. The pulses are administered by passing high currents through an electromagnetic coil placed adjacent to a patient's scalp. The pulses induce an electric field in the underlying brain tissue. When the induced field is above a certain threshold, and is directed in an appropriate orientation relative the brain's neuronal pathways, localized axonal depolarizations are produced, thus activating the neurons in the relevant brain structure.
Standard TMS coils are limited to activation of only cortical brain regions, up to a depth of about 1.5 cm. Hence when treating depression with a standard TMS system, the limbic system, which is related to mood regulation and is generally deeper than 1.5 cm, is only indirectly affected, through secondary processes involving cortical structures, which are directly activated by TMS and then affect the deeper limbic system structures.

A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly

2009-09-08T09:24:00.000-07:00

PMID: 19589195
TITLE: Top cited papers in international psychogeriatrics: 5. A controlled study of repetitive transcranial magnetic stimulation as a treatment of depression in the elderly.
AUTHORS: Ricardo E Jorge, Robert G Robinson
AFFILIATION: Department of Psychiatry, Roy J and Lucille A. Carver College of Medicine, University of Iowa, U.S.A. Email: Ricardo-jorge@uiowa.edu.
REFERENCE: Int Psychogeriatr 2009 Oct 21(5):855-60

Emerging targets for antidepressant therapies

2009-07-27T03:14:00.000-07:00

PMID: 19501541

TITLE: Emerging targets for antidepressant therapies.

AUTHORS: Jeffrey J Rakofsky, Paul E Holtzheimer, Charles B Nemeroff

AFFILIATION: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 2004 Ridgewood Dr, Suite 218, Atlanta, GA 30322, United States.

REFERENCE: Curr Opin Chem Biol 2009 Jun 13(3):291-302

Despite adequate antidepressant monotherapy, the majority of depressed
patients do not achieve remission. Even optimal and aggressive therapy
leads to a substantial number of patients who show minimal and often
only transient improvement. In order to address this substantial problem
of treatment-resistant antidepressant therapy have emerged as a consequence of major advances
in the neurobiology of depression. Three major approaches to uncover
novel therapeutic interventions are: first, optimizing the modulation of
monoaminergic neurotransmission; second, developing medications that
act upon neurotransmitter systems other than monoaminergic circuits; and
third, using focal brain stimulation to directly modulate neuronal
activity. We review the most recent data on novel therapeutic compounds
and their antidepressant potential. These include triple monoamine
reuptake inhibitors, atypical antipsychotic augmentation, and dopamine
receptor agonists. Compounds affecting extra-monoamine neurotransmitter
systems include CRF(1) receptor antagonists, glucocorticoid receptor
antagonists, substance P receptor antagonists, NMDA receptor antagonists
, nemifitide, omega-3 fatty acids, and melatonin receptor agonists.
Focal brain stimulation therapies include vagus nerve stimulation (VNS
), transcranial magnetic stimulation (TMS), magnetic seizure therapy (
MST), transcranial direct current stimulation (tDCS), and deep brain
stimulation (DBS).

Brain Stimulation in Depression Blog

2009-06-16T00:33:00.000-07:00

There is an interesting weblog of Douglas Mental Health University Institute @ McGill which is certainly interesting for the readers of this Blog. Here is the description:

Marcelo T. Berlim, MD, MSc, a researcher and clinical psychiatrist at the Douglas, presents the latest scientific information regarding the use of brain stimulation techniques in major depression, such as repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), transcranial direct current stimulation (tDCS), and vagus nerve stimulation (VNS).
This blog is a resource for mental health professionals, including researchers and is not intended to provide medical consultation/referral and/or personal clinical advices.

You can connect here or in the linklist to the left.

With deep brain stimulation, experts want to tread carefully

2009-06-02T09:32:00.001-07:00

read the article here.

Electrical Brain Stimulation Prompts Big Hopes—and a Dash of Concern

2009-06-02T09:29:00.000-07:00

read the article here.

Implanting Electrodes in the Brain Could Help Treat Severe Depression

2009-06-02T09:28:00.000-07:00

read the article here

Laser-Controlled Humans Closer to Reality

2009-04-30T00:39:00.000-07:00

An interesting take of WIRED magazine on the following article in Neuron:

Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain,” by Xue Han, Xiaofeng Qian, Jacob G. Bernstein, Hui-hui Zhou, Giovanni Talei Franzesi, Patrick Stern, Roderick T. Bronson, Ann M. Graybiel, Robert Desimone and Edward S. Boyden. Neuron 62, 191–198, April 30, 2009.

Read the news article here and link to the original paper here.

Rewiring Faulty Circuits in the Brain

2009-03-30T01:18:00.000-07:00

A wide range of neuropsychiatric disorders seems to respond to deep brain stimulation--but how does it work, and where will it lead?
A very informative article from SCIENCE on the current state of the art of DBS for neuropsychiatric applications. Read it here; download the PDF here; download or hear the podcast here.

A randomized trial of the anti-depressant effects of low- and high-frequency transcranial magnetic stimulation in treatment-resistant depression

2009-03-19T02:38:00.000-07:00

PMID: 19105212
TITLE: A randomized trial of the anti-depressant effects of low- and high-frequency transcranial magnetic stimulation in treatment-resistant depression.
AUTHORS: Paul B Fitzgerald, Kate Hoy, Zafiris J Daskalakis, Jayashri Kulkarni
AFFILIATION: Department of Psychological Medicine, Alfred Psychiatry Research Centre, The Alfred and Monash University, Commercial Rd Melbourne, Vic., Australia.
REFERENCE: Depress Anxiety 2009 26(3):229-34
BACKGROUND: The majority of studies investigating the effectiveness of
repetitive transcranial magnetic stimulation (rTMS) as a treatment for
major depression have focused on high-frequency rTMS to the left
prefrontal cortex (HFL-rTMS). In addition, low-frequency right
prefrontal rTMS (LFR-rTMS) has also been shown to have antidepressant
properties. To date only a small number of studies have directly
compared the efficacy of these two approaches. METHODS: The aim of this
study, therefore, was to investigate further whether LFR-rTMS is as
effective as HFL-rTMS in the treatment of major depression. Twenty-seven
patients were randomized to one of two treatment arms (HFL-rTMS or LFR-
rTMS) for 3 weeks with a possible 1-week extension. Non-responders were
offered the opportunity of crossing over to the other treatment type.
Stimulation parameters for HFL-rTMS were 30 stimulation trains of 5 s
duration at 100% of the resting motor threshold (RMT); for LFR-rTMS,
stimulation was applied in four trains of 180 s duration (30 s inter-
train interval) at 110% of the RMT. Stimulation was provided 5-week days
per week. RESULTS: There were significant improvements seen from
baseline to end point irrespective of group and on all clinical outcome
measures. In addition, there was no deterioration in any of the measures
used to assess cognitive change, and significant improvements were seen
on measures of immediate verbal memory and verbal fluency. CONCLUSIONS
: HFL-rTMS and LFR-rTMS appear to be equally efficacious in treating
major depression. This study adds to the growing literature supporting
LFR-rTMS as an additional viable method of rTMS delivery in the
treatment of depression.

A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression

2009-03-19T02:32:00.000-07:00

PMID: 19145228
TITLE: A randomized trial of rTMS targeted with MRI based neuro-navigation in treatment-resistant depression.
AUTHORS: Paul B Fitzgerald, Kate Hoy, Susan McQueen, Jerome J Maller, Sally Herring, Rebecca Segrave, Michael Bailey, Greg Been, Jayashri Kulkarni, Zafiris J Daskalakis
AFFILIATION: Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd Melbourne, Victoria, Australia. paul.fitzgerald@med.monash.edu.au
REFERENCE: Neuropsychopharmacology 2009 Apr 34(5):1255-62
The aim of this study is to investigate whether repetitive transcranial
magnetic stimulation (rTMS) targeted to a specific site in the
dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method
based on structural MRI, would be more effective than rTMS applied
using the standard localization technique. Fifty-one patients with
treatment-resistant depression were randomized to receive a 3-week
course (with a potential 1-week extension) of high-frequency (10 Hz)
left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days
per week at 100% of the resting motor threshold. Treatment was targeted
with either the standard 5 cm technique (n=27) or using a neuro-
navigational approach (n=24). This involved localizing the scalp
location that corresponds to a specific site at the junction of Brodmann
areas 46 and 9 in the DLPFC based on each individual subject's MRI scan
There was an overall significant reduction in the Montgomery-Asberg
Depression Rating Scale scores over the course of the trial, and a
better outcome in the targeted group compared with the standard
localization group at 4 weeks (p=0.02). Significant differences were
also found on secondary outcome variables. The use of neuro-navigational
methods to target a specific DLPFC site appears to enhance response to
rTMS treatment in depression. Further research is required to confirm
this in larger samples, or to establish whether an alternate method
based on surface anatomy, including measurement from motor cortex, can
be substituted for the standard 5 cm method.

'A Frontier of Medicine': Brain Surgery for Weight Loss

2009-03-12T04:00:00.000-07:00

More on yesterdays story about DBS for obesity here.

Obese woman has brain surgery for weight loss

2009-03-10T14:02:00.000-07:00

Press report on the second patient to get DBS for obesity in the US, read it here. Personally, I am more than a little bit wary about this development ....

A quote from the article:

Poe was awake during the three-hour surgery, in which wires carrying an electrical impulse were inserted into her brain in the region where the stomach is controlled, and linked to two pacemaker devices implanted in her chest. (emphasis added)

The neurosurgeon is quoted as saying:

"This is a frontier of medicine...to be able to generate tiny pulses of electricity in these deep nuclei of the brain, and to see what effect they may have on behavior, including in this case the behavior of eating and the issue of uncontrolled appetite," he said

OpenStim: The Open Noninvasive Brain Stimulator

2009-03-03T00:15:00.000-08:00

An open source rTMS machine ? Read more on this interesting project on the WIKI here.

Smaller, cheaper and more hackable versions of TMS machines are being built. They've put together an open source TMS project that might allow anyone to start an at-home DIY brain hacking lab.

Dial H for Happiness: How Neuroengineering May Change Your Brain

2009-03-03T00:09:00.000-08:00

An interesting article on the work of Dr. Bret Schneider at Stanford Medical School and Dr. Ed Boyden at MIT. Read it here.

Call for Papers for a Special Issue: Transcranial Magnetic Stimulation

2009-03-02T01:26:00.000-08:00

Get more information here.

rTMS Center in California

2009-02-24T04:05:00.000-08:00

M. Bret Schneider, MD

Diplomate, American Board of Psychiatry and Neurology

828 Portola Road

Portola Valley, CA 94028

Telephone (650) 906-8371

Fax (650) 851-3544

Email: MBSchneiderMD@gmail.com

Web: http://mbschneidermd.googlepages.com

Medtronic’s Brain Stimulator Gets FDA Approval for OCD Patients

2009-02-23T07:38:00.000-08:00

Medtronic has just been granted a Humanitarian Device Exemption (HDE) from the FDA for DBS in OCD; read more here.

After Long Wait, Medtronic Starts Big Depression Study

2009-02-22T08:30:00.000-08:00

After a delay, Medtronic has started the the pivotal trial of DBS for major depression, read some more here.
On the protocol:

Medtronic's study will start with enrollment of 30 people at five sites, but there are plans to enroll up to 200 patients from 20 sites. Patients in the study will have a device implanted, but for some patients, the device won't be turned on for the first 16 weeks - this way the trial can be randomized between patients who are receiving treatment and not receiving treatment.

Conference on Neuroprosthetic Devices

2009-02-10T00:54:00.000-08:00

First International Conference on Neuroprosthetic Devices will take place at National Chiao Tung University, Hsinchu, Taiwan on March 19th and 20th, 2009. The mission of this newly founded conference is to foster West-East interaction and collaboration in the rapidly advancing clinical use of neuroprosthetics. The specific aim of the first conference is to expose unique technological and neurological research opportunities in Taiwan. National Chaio Tung University is one of the best universities in Taiwan and is located right next to the world-famous HsinChu Science Park hosting hundreds of biotechnology, semiconductor, and electronics companies. The conference sessions will cover several key areas in the neuroprosthetic development, such as deep brain stimulation for treatment of Parkinson’s disease and epilepsy, devices for restoring hearing and overcoming muscle paralysis, microelectrode biocompatibility, and novel microelectrode technologies. For detailed conference program and registration information, please visit http://www.bsrc.nctu.edu.tw/ICND/.

A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression

2009-02-02T01:27:00.000-08:00

Abstract:
The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subject's MRI scan. There was an overall significant reduction in the Montgomery-Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.Neuropsychopharmacology advance online publication, 14 January 2009; doi:10.1038/npp.2008.233.

Deep Brain Stimulation for Depression

2009-01-26T00:43:00.000-08:00

Summary of the Lozano et al article in Biological Psychiatry. read it here.

The study was in two parts. Six patients were treated with deep brain stimulation in 2005; the new results followed up another 14 people for a year. Researchers found that after getting deep brain stimulation, patients were calmer, had improved moods, and were more interested and motivated in life.

Sparking Recovery with Brain "Pacemakers"

2008-12-29T04:37:00.000-08:00

An excellent article on the state of the art of DBS by Morten L. Kringelbach and Tipu Z. Aziz. Read it here.

Stimulus intensity dependence of cerebral blood volume changes in left frontal lobe by low-frequency rTMS to right frontal lobe: A near-infrared spec

2008-12-29T04:14:00.001-08:00

PMID: 18992287
AUTHORS: Yoshiyuki Aoyama, Naoki Hanaoka, Masaki Kameyama, Masashi Suda, Toshimasa Sato, Mingqiao Song, Masato Fukuda, Masahiko Mikuni
AFFILIATION: Department of Psychiatry and Human Behavior, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Gunma, Japan.
REFERENCE: Neurosci Res 2009 Jan 63(1):47-51
Repetitive transcranial magnetic stimulation (rTMS) has recently been widely employed for the investigation of brain function and treatment of psychiatric and neurological disorders. Although high and low stimulation frequencies are assumed to activate and deactivate brain function, respectively, the optimal parameters of rTMS for treatment of depression have been determined only on the basis of their clinical efficacy. In this study, we administered a 60-s low-frequency rTMS of three grades low intensities over the right dorsolateral prefrontal cortex (DLPFC) in 10 healthy volunteers, and monitored functional changes of the contralateral DLPFC by near-infrared spectroscopy (NIRS) during and immediately after rTMS. Obtained results demonstrated significant [oxy-Hb] decreases during rTMS, and significant differences in the time courses of [oxy-Hb] changes among three stimulus intensities , that is, [oxy-Hb] decreases were most prominent during the latter half of the stimulation and the first 30s of poststimulation only at 15mm condition (58% intensity). These results suggest that monitoring of brain functional changes due to rTMS using NIRS is useful for elucidating the brain mechanisms underlying the clinical effects of rTMS , and the effects of rTMS over contralateral DLPFC are obtained if the stimulus intensities are more than one-half of the motor thresholds.

Daily left prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled clinical trial

2008-12-29T04:12:00.000-08:00

PMID: 18704101
AUTHORS: Sarah H Lisanby, Mustafa M Husain, Peter B Rosenquist, Daniel Maixner, Rosben Gutierrez, Andrew Krystal, William Gilmer, Lauren B Marangell, Scott Aaronson, Zafiris J Daskalakis, Randolph Canterbury, Elliott Richelson, Harold A Sackeim, Mark S George
AFFILIATION: 1Division of Brain Stimulation and Therapeutic Modulation, Department of Psychiatry, Columbia University/New York State Psychiatric Institute, New York, NY, USA.
REFERENCE: Neuropsychopharmacology 2009 Jan 34(2):522-34
Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham- controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery- Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.Neuropsychopharmacology (2009) 34, 522- 534; doi:10.1038/npp.2008.118; published online 13 August 2008.

Repetitive TMS combined with exposure therapy for PTSD: A preliminary study

2008-12-29T04:08:00.000-08:00

PMID: 18455908
AUTHORS: Elizabeth A Osuch, Brenda E Benson, David A Luckenbaugh, Marilla Geraci, Robert M Post, Una McCann
AFFILIATION: Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MA, United States.
REFERENCE: J Anxiety Disord 2009 Jan 23(1):54-9
Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment- refractory PTSD were studied in a placebo-controlled, crossover design of imaginal exposure therapy with rTMS (1Hz) versus sham. PTSD symptoms , serum and 24h urine were obtained and analyzed. Effect sizes for PTSD symptoms were determined using Cohen's d. Active rTMS showed a larger effect size of improvement for hyperarousal symptoms compared to sham; 24-h urinary norepinephrine and serum T4 increased; serum prolactin decreased. Active rTMS with exposure may have symptomatic and physiological effects. Larger studies are needed to confirm these preliminary findings and verify whether rTMS plus exposure therapy has a role in the treatment of PTSD.

Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-control

2008-12-29T04:06:00.000-08:00

PMID: 18447962
AUTHORS: D J L G Schutter
AFFILIATION: Experimental Psychology, Utrecht University, Utrecht, The Netherlands.
REFERENCE: Psychol Med 2009 Jan 39(1):65-75
BACKGROUND: For more than a decade high-frequency repetitive transcranial magnetic stimulation (rTMS) has been applied to the left dorsolateral prefrontal cortex (DLPFC) in search of an alternative treatment for depression. The aim of this study was to provide an update on its clinical efficacy by performing a meta-analysis involving double -blind sham-controlled studies.MethodA literature search was conducted in the databases PubMed and Web of Science in the period between January 1980 and November 2007 with the search terms 'depression' and ' transcranial magnetic stimulation'. Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included. A random effects meta-analysis was performed to investigate the clinical efficacy of fast-frequency rTMS over the left DLPFC in depression. RESULTS: The test for heterogeneity was not significant (QT=30.46, p=0.39). A significant overall weighted mean effect size, d=0.39 [95% confidence interval (CI) 0.25-0.54], for active treatment was observed (z=6.52, p<0.0001). Medication resistance and intensity of rTMS did not play a role in the effect size. CONCLUSIONS: These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents. Current limitations and future prospects are discussed.

Vagus Nerve Stimulation, Does it Work?

2008-11-24T01:24:00.000-08:00

Daban and coauthors recently reviewed data on efficacy of VNS in theJournal of Affective Disorders:

Objective: The main objective of this review of the literature was to evaluate the safety and efficacy of Vagus Nerve Stimulation (VNS) in treatment-resistant depression (TRD) by means of systematic review and meta-analysis.
Methods: A systematic review of the literature was made using the major databases (Medline, Psychological Abstracts, Current Contents), beginning in January 2000 and ending in September 2007. Ninety-eight references were found, but only 18 add-on studies met the required quality criteria and were included in this review. Only one double-blind, randomized study was available and therefore a meta-analysis was not feasible.
Results: In a majority of the preliminary open studies selected for this review, VNS was associated with a significant reduction of the depressive symptoms (primary outcome: Hamilton Depression Rating Scale, HDRS) in the short and long term. Unfortunately, the only double-blind study gave rather inconclusive results. Generally, VNS is reported to be a safe and feasible procedure, despite its invasive nature.
Conclusions: VNS seems to be an interesting new approach to treating TRD. However, despite the promising results reported mainly in open studies, further clinical trials are needed to confirm its efficacy in major depression. Moreover, studies on its mechanism of action and cost-effectiveness are also required to better understand and develop VNS therapy for affective disorder.

Address update for Mindcare in Canada

2008-11-12T05:43:00.000-08:00

Deanna Bertoia

Manager of Clinic Development

Ottawa/Toronto MindCare Centre

Local Ottawa: 613.569.7867

Local Toronto: 647.344.7867

Toll-free: 1.888.726.7867

Fax: 613.715.5833

Deanna{at}mindcarecentres.com

www.mindcarecentres.com

Remote Excitation of Neuronal Circuits Using Low-Intensity, Low-Frequency Ultrasound

2008-11-05T01:58:00.000-08:00

A group of neuroscientists at Arizona State University has developed pulsed ultrasound techniques that can remotely stimulate brain circuit activity. Read the open source article here.

A new implantable Neurostimulator ?

2008-11-05T01:28:00.000-08:00

Texcel Introduces Innovative Programmable, Implantable Stimulation System for R&D of Specialty Stimulation Therapies

Last update: 3:15 p.m. EDT Oct. 29, 2008

EAST LONGMEADOW, Mass., Oct 29, 2008 /PRNewswire via COMTEX/ -- Texcel, a leading provider of custom medical device development and manufacturing solutions, has introduced its innovative new StimX programmable, implantable stimulation system.
Designed for use in the research and development of specialty stimulation therapies, the StimX system is the industry's first-truly programmable, implantable customizable platform.
The StimX system's programmable stimulation parameters "will directly benefit medical researchers and medical device developers by dramatically reducing the time, cost, and risk involved in creating devices for use in testing stimulation therapies in a variety of applications," said Keith Checca, Texcel Director of Business Development.
"With the StimX implantable system, we are freeing researchers from the hours and dollars that they'd otherwise invest in designing and developing their own devices -- and to literally re-allocate their resources back into their research," said Checca.
Neural stimulation therapies, including direct nerve and brain stimulation, are used to treat people who suffer from epilepsy, Parkinson's disease, clinical depression and other diseases. Targeted stimulation areas range widely from direct brain surface, deep brain stimulation, to the spinal cord and peripheral nerves.
Texcel's new StimX platform includes an implantable stimulator, laptop and output customization program, proven wireless communication and charging modules.
The need for the system was realized as a result of Texcel's years of innovation in the field of custom medical device manufacturing and it was made possible by Texcel's partnerships with medical electronics development resources.
For more information, visit the Texcel website at: http://www.texcelmedical.com/stimx; or call the company at (413) 525-5700.

FDA Clears TMS Therapy for the Treatment of Depression

2008-10-09T09:47:00.000-07:00

Finally, 3 years after the first presentation of the trial data at the 2005 ACT meeting and one year after the publication of the results in Biological Psychiatry by Jonny O'Reardon the manufacturer Neuronetics got the treatment approved by the FDA for

for the treatment of Major Depressive Disorder in adult patients who have failed to achieve satisfactory improvement from one prior antidepressant medication at or above the minimal effective dose and duration in the current episode.

If you want to read the PDF of the full press release click here (beware, language geared to potential investors...).

In order to convince the manufacturer had to do an additional trial. If you want some more information on the development history read the excellent summary from the blog Brain Stimulant.

Cyberonics Hasn't Found Depression-Business Partner

2008-10-03T12:48:00.000-07:00

Normally I do not read business pages - but this is interesting for our scientific field. CNNMoney.com writes on the business outlook of Cyberonics for the depression indication. Overall the future does not seem too bright right now:

The need for a trial, plus the need to convince insurers, suggests it could take years before the depression business has a chance to speed up, said analyst Brozak, who has a sell rating on Cyberonics. In today's financial markets, that is a long and uncertain investment horizon for potential partners, he said.

6 Different Locations for Deep Brain Stimulation in Depression

2008-09-22T10:34:00.000-07:00

The Dutch Psychiatrist Walter van den Broek runs under the pseudonym Dr. Shock MD, PhD an excellent weblog on peer reviewed data on neurostimulation.

We would like to point out 2 great post on putative neuromodulation targets for depression:

Coating Improves Electrical Stimulation Therapy Used For Parkinson's, Depression, Chronic Pain

2008-09-18T08:13:00.000-07:00

ScienceDaily (Sep. 18, 2008) — Researchers at UT Southwestern Medical Center have designed a way to improve electrical stimulation of nerves by outfitting electrodes with the latest in chemically engineered fashion: a coating of basic black, formed from carbon nanotubes.

The nanotube sheathing improves the signals received and transmitted by electrodes, which researchers say is a potentially critical step for advancing electrical nerve stimulation therapy. This type of therapy increasingly shows promise for diseases ranging from epilepsy to depression to chronic leg and back pain.
By implanting electronic nerve stimulators, doctors elsewhere have provided a quadriplegic patient with the ability to move a computer cursor at will, and monkeys have been able to move objects in a virtual world with mere mind power. For individuals who lose an arm or leg and rely on prosthetics, implanted stimulators offer promise in restoring feelings of sensation.

"The key to success for these types of brain-machine interfaces is where the electrode meets the nerve tissue," said Dr. Edward Keefer, instructor of plastic surgery at UT Southwestern and lead author of the study appearing in a recent issue of Nature Nanotechnology. "When we coat the electrodes with carbon nanotubes, it improves the stimulation of the nerve and the feedback from the sensors."

Depending on the way the nanotubes are fashioned, researchers were able to bolster either the stimulation or receptive capabilities to improve performance. In some tests, the nanotube coating improved performance by fortyfold, while in others it improved by a factor of as much as 1,600.

Nanotubes look like lattices rolled into a tube on a microscopic scale. Although they are 1/50,000 the width of a human hair, nanotubes are nonetheless among the stiffest and strongest fibers known, as well as excellent conductors of electricity.

Those properties proved to be just the attributes needed to help electrophysiologists conquer some of the hurdles facing them – issues such as battery power and chemical stability.

The carbon nanotube coating improves conductivity, which means less energy is needed to power the nerve stimulator. That can help reduce routine maintenance, such as the need to change batteries in implanted stimulation devices, as well as reduce tissue damage caused by the electrical charge.
"Our process is like taking a Ford Pinto, pouring on this chemical coating, and turning it into a Ferrari," Dr. Keefer said.

Researchers have tried several types of electrochemical coatings to see if they could improve conductivity, but the coatings often break down quickly or fail to stay affixed to the electrodes. The carbon nanotube coating shows far more promise, although further research is still needed, Dr. Keefer said.

"The development of new technologies by Dr. Keefer to potentially restore function in wounded tissues and future transplantations is exciting," said Dr. Spencer Brown, assistant professor of plastic surgery who heads research in the Nancy Lee and Perry R. Bass Advanced Plastic Surgery and Wound Healing Laboratory at UT Southwestern.

Other UT Southwestern researchers involved with the study include Dr. Barry Botterman, associate professor of cell biology, and Dr. Mario Romero-Ortega, assistant professor of plastic surgery. Researchers from Texas Scottish Rite Hospital for Children, Vanderbilt University and the University of North Texas also participated. The research was supported in part by Dallas-based Plexon, Inc

Adapted from materials provided by UT Southwestern Medical Center.

Functional Neurosurgery in the Treatment of severe Obsessive Compulsive Disorder and Major Depression

2008-09-17T04:03:00.000-07:00

Functional Neurosurgery in the Treatment of severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician

An excellent review article by Dhwani B. Shah, MD; Angeliki Pesiridou, MD; Gordon H. Baltuch, MD, PhD; Donald A. Malone, MD; and John P. O’Reardon, MD which you can access here.

Psychiatry (Edgemont) 2008;5(9):24–33

Brain pacemakers give jolt to hard-to-treat illnesses

2008-09-08T07:22:00.000-07:00

Another DBS article in the Chicago Tribune.

Read it here.

Many illnesses may be in for a shock

2008-09-08T07:19:00.000-07:00

An interesting article appeared today in the Chicago Tribune.

Read it here.

Transcranial Stimulation Improves Memory in Alzheimer's Disease

2008-09-04T02:49:00.000-07:00

By Will Boggs, MD

NEW YORK (Reuters Health) Aug 22 - Transcranial direct current stimulation (tDCS) improves recognition in patients with Alzheimer disease, according to a report in the August 12th issue of Neurology.

"Our preliminary data on Alzheimer's disease patients are promising as we observed beneficial effects after a single tDCS session, suggesting that chronic daily application might induce even greater improvement," Dr. Alberto Priori from the University of Milan told Reuters Health. "Our studies encourage broader research programs using different stimulation protocols and longer clinical follow-up to clarify the impact therapy might have on patients' daily functional activities."

Dr. Priori and colleagues investigated whether anodal tDCS (which generally increases the function of the underlying areas of the cerebral cortex) applied over the temporoparietal cortex could improve recognition memory in 10 patients with Alzheimer's disease.

Anodal tDCS significantly improved word recognition memory accuracy, the authors report, whereas cathodal tDCS (which generally suppresses the function of the underlying cerebral cortex) significantly worsened it. Sham tDCS had no impact on memory.

The results were similar after correcting memory performance for guessing, the report indicates.

Neither anodal tDCS nor cathodal tDCS induced specific changes in the attention task, compared with sham tDCS, the researchers note.

"Interestingly," the investigators say, "the tDCS-induced improvement in the word recognition test we observed in patients with Alzheimer's disease is comparable to the 16% improvement induced by long-term pharmacologic treatment with cholinesterase inhibitors."

"We are assessing possible long-lasting effects of tDCS in Alzheimer's disease patients using repeated session protocols in a larger sample with longer clinical follow-up," Dr. Priori said.

"We believe that the best results, especially in Alzheimer's disease patients, could be obtained by combining tDCS with cognitive rehabilitation," Dr. Priori added.

Neurology 2008;71:493-498.

Acupuncture for Psychiatric Illness: A Literature Review

2008-09-01T06:26:00.000-07:00

I guess this is brain stimulation also ...

Cortical stimulation for Depression

2008-09-01T05:53:00.000-07:00

A rather interesting transcript of a conference call for investors of Northstar Neuroscience, Inc. (NSTR). A quotation from this transcript:

There's a great deal of attention and focus on devices with the potential to treat severe depression. And this area is widely considered to be one of the biggest future opportunities in medical technology. In particular, there is considerable scientific evidence to support neurostimulation as an effective treatment for this population. Electroconvulsive shock treatment is administered to over 100,000 patients annually, even though its effects can be transient and patients can experience significant side effects such as memory loss.

and another, (which I certainly do not agree with...)

Cortical stimulation is much less invasive than deep brain stimulation treatments currently being studied.

Read here.

Jolting the brain fights deep depression

2008-08-22T09:00:00.001-07:00

This is a how CNN explains Deep Brain Stimulation for Depression.

Link to the article here.

Vagus nerve stimulation a treatment option, but not for everyone

2008-08-15T03:22:00.000-07:00

MayoClinic.com published a short summary on the current state of Vagus Nerve Stimulation (VNS) intended for patient information. Other interesting links on Neurostimulation from their site are:

Deep Brain Stimulation Studied for Depression

2008-08-15T03:06:00.000-07:00

Jun Yan writes in Psychiatric News about Dr. Helen Maybergs lecture at the APA in May 2008 in which she presented the data of her cg25 DBS depression study.

Psychiatric News June 20, 2008

Medtronic: Tapping the Brain for Profit

2008-08-11T00:51:00.000-07:00

Very interesting article in US News & World Report on how neuromodulation is going to be crucial for the economic development of device manufacturers.

'moving from heart to head'.....

Brain electrodes tackle severe depression

2008-08-07T02:28:00.000-07:00

This is another excellent writeup of the Lozano/Mayberg study in the Nature News section.

Trial shows success for ‘deep brain stimulation’ technique.
Abbott Alison
Severely depressed patients who do not respond to conventional therapy may be helped by deep brain stimulation (DBS), according to the most-extensive study to date of the experimental procedure.
In a clinical trial in Toronto, Canada, 12 out of 20 patients who had stimulating electrodes placed in a brain area called the subcallosal cingulated gyrus showed significant improvement in their depression, with seven of them going into full remission.
The benefits lasted at least a year, according to the results published this week in the journal Biological Psychiatry1. Patients in the study had failed to respond to cognitive therapy, antidepressant drugs and electroconvulsant therapy.

Lasting effect
The research team published results of DBS on their first six patients in 20052. Four of those patients responded well, and were still showing significant improvement after the trial finished six months later. The new research represents the largest trial on DBS for depression to follow patients for a full year.
“It is a remarkable that so many patients got well and stayed well,” says Helen Mayberg, now at Emory University, Atlanta, Georgia, who helped to develop the therapy.

“Brain surgery is not like getting your nails done, so it is important to try to find out who will benefit.”
Helen Mayberg

“Some patients had to face personal traumas during this period, such as deaths and bankruptcy, but handled them normally — they had a normal dynamic range of feeling,” says neurosurgeon Andres Lozano, of the University of Toronto, who led the study.

Advanced Neuromodulation Systems, a company based in Piano, Texas, that makes DBS electrodes, is now sponsoring a double-blind, controlled phase III trial on up to 200 patients at three centres in the United States.
Participants in the study, called BROADEN (Brodmann Area 25 Deep Brain Neuromodulation), will have DBS devices implanted, targeting the same part of the brain as the Canadian study. Half of the devices will be switched on immediately after surgery, while the other half will wait for six months before being stimulated. Neither the patients nor the scientists and clinicians will know who is switched on at any particular time. The study is expected to take several years to complete.

More than a manicure
“In the meantime we need to know why some of the patients don’t respond at all,” says Mayberg. “Are we missing the target, or are there different subtypes of the disease?” Her team is now trying to find out how to identify those who will respond to DBS, and those who won’t. “Brain surgery is not like getting your nails done, so it is important to try to find out who will benefit.”
Other centres in Germany, Belgium and the Cleveland Clinic in Ohio are also doing DBS trials in depression, but they use slightly different targets in the brain. Neurologists think that the therapy works by activating or damping down particular brain circuits. At the moment, no-one knows which of the targets within these circuits will eventually prove to be the most optimal. “It’s important to have different approaches during these early days of the therapy,” says Mayberg.
The German study, for example, uses the nucleus accumbens. Psychiatrist Thomas Schlaepfer of the University of Bonn says that most of the ten patients studied by the team so far are responding well. “Our patients have been selected from the worst of the worst — people who have been continually depressed for twenty years or more,” he says. “For a psychiatrist it is amazing to see that many of the patients have no symptoms at all any more — although two showed no response at all.”
All Schlaepfer's responders have become very motivated to take up activities instead of lying in bed, he says. The centres are also investigating the value of DBS in other psychiatric disturbances, such as obsessive compulsive disorder and addiction.
References

Lozano, A. M. et al. Biol. Psychiatry doi: 10.1016/jbiopsych.2008.05.034 (2008).

Mayberg, H. S. et al. Neuron 45, 651–660 (2005).

Mending a broken mind

2008-08-06T04:36:00.000-07:00

Another press article by Globe and Mail (Canada) on the Lozano/Mayberg study.

A cure for depression?

2008-08-06T04:26:00.000-07:00

A nice write-up on the DBS depression study published recently in Biological Psychiatry by Andres Lozanno, Helen Mayberg et al. Find the article here and the link to the original article here.

Cost-effectiveness of transcranial magnetic stimulation vs. electroconvulsive therapy for severe depression: A multi-centre randomised controlled tria

2008-07-17T06:40:00.000-07:00

PMID: 18262655
AUTHORS: Martin Knapp, Renee Romeo, Andrew Mogg, Savitha Eranti, Graham Pluck, Rick Purvis, Richard G Brown, Robert Howard, Michael Philpot, John Rothwell, Denzil Edwards, Declan M McLoughlin
AFFILIATION: Centre for the Economics of Mental Health, King's College London, Institute of Psychiatry, United Kingdom; Personal Social Services Research Unit, London School of Economics, United Kingdom.
REFERENCE: J Affect Disord 2008 Aug 109(3):273-85
BACKGROUND: Electroconvulsive therapy (ECT) has a long history of use in treating depression. Repetitive transcranial magnetic stimulation (rTMS ) has been introduced more recently to the treatment spectrum. Its cost- effectiveness has not been explored. METHOD: Forty-six right-handed people with severe depressive episodes referred for ECT were randomised to receive either ECT twice weekly or rTMS on consecutive weekdays. Health and other service use were recorded for retrospective periods of 3 months prior to initiation of treatment and during the 6 months following the end of allocated treatment. Costs were calculated for the treatment period and the subsequent 6 months, and comparisons made between groups after adjustment for any baseline differences. Cost- effectiveness analysis was conducted with incremental change on the 17- item Hamilton Rating Scale for Depression (HRSD) as the primary outcome measure, and quality-adjusted life years (based on SF6D-generated utility scores with societal weights) as secondary outcome, cost- effectiveness acceptability curves plotted.
RESULTS: Based on the HRSD scores and other outcome measures, rTMS was not as effective as ECT. The cost of a single session of rTMS was lower than the cost of a session of ECT, but overall there were no treatment cost differences. In the treatment and 6-month follow-up periods combined, health and other service costs were not significantly different between the two groups. Informal care costs were higher for the rTMS group. Total treatment, service and informal care costs were also higher for the rTMS group. The cost-effectiveness acceptability curves indicated a very small probability that decision-makers would view rTMS as more cost-effective than ECT.
LIMITATIONS: Small sample size, some sample attrition and a relatively short follow-up period of 6 months for a chronic illness. Productivity losses could not be calculated.
CONCLUSIONS: ECT is more cost-effective than rTMS in the treatment of severe depression.

Electromagnetic Treatments for Depression Seek to Improve on ECT

2008-07-10T05:03:00.000-07:00

medpage TODAY publised a nice summary of neuromodulatory approaches for depression. The following topics are discussed:

Vagus nerve stimulation
Magnetic seizure therapy
Repetitive transcranial magnetic stimulation
Deep brain stimulation
Transcranial direct current stimulation
Implantable cortical stimulation

The new(er) kid on the block is obviously Implantable cortical stimulation, the author writes about this technique:

Another early-stage investigational technology takes vagus nerve stimulation a step farther. Instead of delivering electrical pulses to a nerve, it sends them to the surface of the brain. Seattle-based Northstar Neurosciences is testing a system that, like vagus nerve stimulation, inserts a pulse generator in the patient's chest. An electrical lead is passed into the skull through a surgically drilled hole, terminating on the dural membrane over the cortex.

DBS for body dysmorphic disorder

2008-07-10T04:59:00.000-07:00

An interesting case report:

Body dysmorphic disorder is excessive preoccupation with minor or imagined flaws in appearance. Dr. Anderson’s patient was a 20-year-old man who obsessed on perceived flaws with his nose and other facial features. He had attempted suicide once, and described his life as a “living hell.” Eight months after DBS surgery, the patient reported mild depression and obsessive compulsive disorder, but no symptoms of body dysmorphic disorder.

The full article can be found on Psych Central.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience

2008-07-02T04:45:00.000-07:00

Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB, Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ.

[1] 1Department of Psychiatry and Human Behavior, Division of Neurosurgery, Butler Hospital, Brown Medical School, Providence, RI, USA [2] 2Department of Clinical Neurosciences, Division of Neurosurgery, Butler Hospital, Brown Medical School, Providence, RI, USA.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Molecular Psychiatry advance online publication, 20 May 2008; doi:10.1038/mp.2008.55.

PMID: 18490925 [PubMed - as supplied by publisher]

Magnetic Pulses Zap Migraine Pain

2008-06-30T03:02:00.000-07:00

BOSTON, June 27 -- For patients who get migraine with aura, a hand-held magnetic device about the size and shape of a hairdryer can zap the pain before it starts, a researcher said here.

Used at the aura stage, the transcranial magnetic stimulation device was nearly twice as likely as a sham treatment to reduce the incidence of a full migraine headache, according to Yousef Mohammad, M.D., of Ohio State University Medical Center in Columbus.

The industry-sponsored phase III randomized double-blind trial follows earlier research that showed the magnetic stimulation process was effective when used in a hospital setting, Dr. Mohammad told attendees at the American Headache Society meeting.

Dr. Mohammad said the device -- which sends two one-Tesla magnetic pulses into the back of the head -- is also safe, with no serious adverse events attributed to it.

"It feels like a slight pressure at the back of the head and that's it," he said.

The theory is that the magnetic pulses interrupt a process called cortical spreading depression, now thought to be the underlying mechanism for migraine with aura, he said.

A similar technique is being tested in patients with depression.

For this study, patients were randomized to a device that emitted the magnetic pulses or to a sham machine. They were told to use the device when the migraine aura began and to record their pain intensity and symptoms at time of treatment and again 30 minutes, one hour, two hours, 24 hours, and 48 hours later.

The intent-to-treat population of 164 patients had a mean age of 39 and 79% were women. Most patients treated themselves while still pain-free or with mild pain (31% and 40%, respectively) but 23% had moderate pain and 6% said their pain was already severe before they used the machine.

The primary endpoint of the study was absence of pain at the two-hour mark, Dr. Mohammad said, where 39% of the active treatment group had no pain, compared with 20% of those using the sham machine.

The difference was significant at P<0.018, he said.

Rates of symptoms such as nausea, photophobia, and phonophobia in the active treatment group were equal to or lower than those seen in the group using the sham machine, according to Dr. Mohammad.

Because of the lack of adverse events and the previously established safety of the transcranial magnetic stimulation device, he said, "this is a promising treatment for migraines with aura."

He added that it also sets the stage for research in migraines without aura.

The device is not yet approved by the FDA, Dr. Mohammad said, but the okay could come within the next six months, based on the current trial.

He added that medical treatments for migraine with aura work in only about half of all patients and some of those can't tolerate the drugs. "There is a definite need for alternatives," Dr. Mohammad said.

The study was supported by NeuraLieve Inc., of Sunnyvale, Ca., manufacturer of the device. Dr. Mohammad serves on the company's medical advisory board

Primary source: AHS Meeting

Secondary Source: medpageTODAY®
Source reference:
Lipton RB, et al “Transcranial Magnetic Stimulation (TMS) using a portable device is effective for the acute treatment of migraine with aura: Results of a double-blind, sham controlled, randomized study” AHS Meeting 2008; LB abstract 450026.

St. Jude gets depression study under way

2008-06-27T08:01:00.000-07:00

CHICAGO, June 26 (Reuters) - St. Jude Medical Inc (STJ.N: Quote, Profile, Research) said on Thursday that the first two patients had received its pacemaker-like implant as part of a clinical study to determine whether deep-brain stimulation will help people with severe depression.

A 59-year-old woman and a 42-year-old man were implanted with the St. Jude Medical Libra Deep Brain Stimulation System, an investigational device, at Alexian Brothers Behavioral Health Hospital in Chicago, the company said.

The stopwatch-sized device is implanted in the chest, with leads that send electrical impulses to specific parts of the brain thought to be involved in depression.

St. Jude's study is researching a specific area in the brain called Brodmann Area 25 that is thought to play a role in depression. Brain imaging studies indicate that Brodmann Area 25 appears to be overactive in severely depressed people.

Medtronic Inc (MDT.N: Quote, Profile, Research) is also investigating whether its device, commonly known as a "brain pacemaker," can help severely depressed patients.

The National Institute of Mental Health estimates that more than 21 million U.S. adults suffer from some kind of depressive disorder. Current therapies are effective for about 80 percent of this patient population, according to the National Advisory Mental Health Council, leaving about 4 million adults who do not respond to medication, psychotherapy or electroconvulsive therapy.

Shares of St. Jude, which also makes cardiac pacemakers and implantable cardioverter defibrillators, were down 83 cents, or 2 percent, at $40.42 at midday amid a weaker broad market. (Reporting by Debra Sherman; Editing by Maureen Bavdek)

TMS Treatment Program at UPenn

2008-06-13T10:03:00.000-07:00

John P.O'Reardon and colleagues describe their TMS Treatment program on this site.

You can contact them here.

Job Offer - Ph.D Scholarship in Neuroscience - Neuroplasticity and TMS

2008-06-11T00:44:00.000-07:00

Ph.D Scholarship in Neuroscience - Neuroplasticity and TMS

School of Psychiatry, University of New South Wales, Sydney, Australia

The School of Psychiatry at UNSW invites applications for a Ph.D. Scholarship investigating mechanisms of Neuroplasticity, to commence in the 2nd half of 2008. Each scholarship is for $27,500 p.a. for a maximum of 3 years,

The Scholarship will focus on the use of transcranial magnetic stimulation (TMS) and other techniques to investigate mechanisms of neuroplasticity in health, ageing and psychiatric disorders. This scholarship is offered as part of the Brain and Ageing Program, UNSW, a high profile research program funded by the NH&MRC, which aims to evaluate the determinants of age-related cognitive disorders. The successful doctoral student will be working with Professors Colleen Loo and Perminder Sachdev, researchers with a track record in brain stimulation techniques, in conjunction with neurophysiology collaborators, based in Randwick, Sydney.

Applicants are encouraged from students/researchers from a variety of backgrounds, including but not limited to medicine, psychology, neurophysiology and neurology.

For further details, please contact Assoc. Prof Colleen Loo (by phone +61-2-9113 2039, or email.

Brainsway reports interim results for bi-polar treatment

2008-06-06T03:14:00.000-07:00

Participants in the study had not responded to previous drug treatments.
Globes correspondent 5 Jun 08 16:39
Medical device company Brainsway Ltd. (TASE:BRIN) has reported the interim results of the trial of its Deep Transcranial Magnetic Stimulation (TMS) device in the treatment of bio-polar disorder (manic depressive) patients at the Shalvata psychiatric hospital who did not respond to other treatments.
The results showed a satisfactory response among patients who had previously been treated with antidepressants, and who did not report any side effects during the trial. 80% of the patients responded to treatment, with more than 50% reporting a significant improvement, using the various depression measurement scales.

Our fellow weblog Brain Stimulant has an interesting comment on these results.

Neural Stimulation Successfully Treats Depression in Patients With Prior Ablative Cingulotomy

2008-06-03T05:36:00.000-07:00

A clinical case conference in the American Journal of Psychiatry by Nejmat et al.

From the abstract:

In this article, we describe the case of a patient who, under the direction of a multidisciplinary case committee, underwent both an ablative cingulotomy and subsequent bilateral deep brain stimulation placement in the Cg25 area. Review of this case provides a means of comparing the two techniques and of illustrating what we feel are some important advantages to using stimulation in the treatment of major depression. This report also provides potential insight into common and unique mechanisms mediating the two procedures.

Lifting the Veil of Depression

2008-05-30T07:12:00.000-07:00

Experimental Electrical Pulse Therapy Can Shift Moods, Possibly Cure Depression

The take of ABC News (Health Section) on DBS Depression date from the Cleveland Clinic, read it here.

TMS Study Center in Stanford

2008-05-28T06:13:00.000-07:00

M. Bret Schneider, MD
Consulting Assistant Professor of Psychiatry and Neurosurgery
Stanford University School of Medicine
Private Practice Psychiatry
701 Welch Road, Suite 211
Palo Alto, CA 94304
Telephone (650) 906-8371
Fax (650) 851-3544
Email: MBSchneiderMD{@}gmail.com
Web: http://mbschneidermd.googlepages.com/home

Scientists test brain pacemakers for depression

2008-05-26T14:44:00.000-07:00

An article on Helen Maybergs work recently communicated at the APA meeting in Washington communicated by the

Treatment-resistant depression: Explore options when depression won’t go away

2008-05-25T07:05:00.000-07:00

A summary on TRD from www.depression-anxiety.org/.

A Gentler Way to Jump-Start the Brain

2008-05-25T06:56:00.000-07:00

Deeply affected: Patients with severe depression may find relief with the help of a wired helmet (above). A magnetic field generated by the helmet harmlessly induces electric currents deep in the brain, giving underactive neurons a much-needed jump start.

Credit: Brainsway

Scientists in Israel are testing a noninvasive method to electrically stimulate neurons deep in the brain.

An article in Technology Review on Deep Transcranial Magnetic Stimulation.

Deep Brain Stimulation Helps Severely Depressed

2008-05-07T23:24:00.000-07:00

The Washington Post write up of the data presented at the ANS meeting.

Treatment-Resistant Depression Responds to Deep-Brain Stimulation: Presented at AANS

2008-05-06T04:30:00.000-07:00

This is an interesting time for Deep Brain Stimulation in Depression!

Dr. Ali Rezai presented data of DBS to the ventral internal capsule/ventral striatum in 17 patients and reported that 47.1% of patients responded to DBS at 6 months based on MADRS criteria, with an increase of up to 50% of the patients responding at 1 year.

Results of Brodmann Area 25 Deep Brain Stimulation Pilot Study Offer Hope for Patients with Severe Depression

2008-05-06T04:24:00.000-07:00

Dr. Helen Mayberg presented further results of DBS to cg25 at the APA Meeting in Washington. She found that 6 months after the procedure, 56 percent of the patients experienced at least a 40 percent decrease in depressive symptoms.

Deep Transcranial Magnetic Stimulation - Putative Uses

2008-05-06T04:20:00.000-07:00

An interesting discussion of possible uses of this new stimulation technique in Alzheimer's disease, depression and schizophrenia. read it here.

St. Jude wins patent on depression treatment

2008-04-28T01:21:00.000-07:00

St. Jude has been awarded a patent for DBS to cg25 for Major Depression, read the newsbrief here and here (FDANews).