Saturday, January 18, 2014

BROADEN Trial of DBS for Treatment-Resistant Depression Halted by the FDA

Webpage for the BROADEN™ study formerly run by St. Jude Medical

It's become mainstream these days to say that psychiatric disorders are neural circuit disorders. You can even read all about it in the New York Times! Cognitive training and neuromodulation (“electroceuticals”) are in, and pharmaceuticals are out, as explained by NIMH Director Dr. Tom Insel in a blog post about the Ten Best of 2013:
...if mental disorders are brain circuit disorders, then successful treatments need to tune circuits with precision. Chemicals may be less precise than electrical or cognitive interventions that target specific circuits.

One of the first to champion this position was Dr. Helen Mayberg and her colleagues, who conducted a small trial using deep brain stimulation (DBS) as a treatment for intractable depression (Mayberg et al., 2005). The technique has been heralded as a potential breakthrough in psychiatry, with $70 million in BRAIN Initiative funding going to DBS development. So a recent tweet announcing the failure of a major clinical trial garnered a lot of attention.

The December 13, 2013 issue of the Neurotech Business Report had the scoop:
The news that St. Jude Medical failed a futility analysis of its BROADEN trial of DBS for treatment of depression cast a pall over an otherwise upbeat attendance at the 2013 NANS meeting. Once again, the industry is left to pick up the pieces as a promising new technology gets set back by what could be many years.

It’s too early to assess blame for this failure. It’s tempting to wonder if St. Jude management was too eager to commence this trial, since that has been a culprit in other trial failures. But there’s clearly more involved here, not least the complexity of specifying the precise brain circuits involved with major depression. Indeed, Helen Mayberg’s own thinking on DBS targeting has evolved over the years since the seminal paper she and colleague Andres Lozano published in Neuron in 2005, which implicated Cg25 as a lucrative target for depression. Mayberg now believes that neuronal tracts emanating from Cg25 toward medial frontal areas may be more relevant. Research that she, Cameron McIntyre, and others are conducting on probabilistic tractography to identify the patient-specific brain regions most relevant to the particular form of depression the patient is suffering from will likely prove to be very fruitful in the years ahead.

But it was hard to find any other information about the failed trial. I can't be sure, but I think this is the study in A Clinical Evaluation of Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression. The sponsor is St. Jude Medical. The record hasn't been updated since March 2013.

BROADEN is a tortured acronym for BROdmann Area 25 DEep brain Neuromodulation.

The July 30, 2013 version of the BROADEN website is preserved at

The BROADEN (BROdmann Area 25 DEep brain Neuromodulation) study is a study to evaluate the safety and effectiveness of deep brain stimulation in patients with a severe form of depression known as Major Depressive Disorder (MDD) who have not responded to multiple treatments. Stimulation to the brain is provided by a surgically implanted medical device called a deep brain stimulation (DBS) system. The system provides stimulation directly to an area of the brain known as Brodmann Area 25 (sometimes referred to as BA25). The study will build upon the depression work of a research team from the University of Toronto, led by neurologist Helen S. Mayberg, M.D. and neurosurgeon Andres Lozano, M.D., PhD, FRCSC.

On January 10, 2014 an Anonymous commenter at DBS Trial1 said:
Regarding the Broaden Study, I'm not writing it off entirely but things aren't looking good. The FDA has put the brakes on the study so it will not enroll any new participants.
While the study is over a year old, the results so far are not encouraging and the device manufacturer is scaling back on monitoring and programming.
It appears that a possible major misstep was made, by not including fMRI mapping prior to implanting the electrodes. 

As Neurotech Business Report (NBR) mentioned, more precise mapping of the white matter connections of the subgenual cingulate (Brodmann area 25) may be essential (e.g., Johansen-Berg et al., 2008). To determine the anatomical connectivity of the subgenual cingulate region, those authors performed tractography (using diffusion-weighted magnetic resonance imaging) to trace the pathways mediating treatment response with DBS. They compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow).

Fig. 3 (Johansen-Berg et al., 2008). Connectivity-based parcellation of anterior cingulate cortex (ACC) and location of electrode contacts. Effective electrode locations are mainly localized within the sACC subregion.

A July 11, 2011 News Release from St. Jude Medical announced that the FDA had approved an expansion of the BROADEN Trial so that up to 20 different sites could enroll a total of 125 patients. There were only three sites originally Chicago, New York City and Dallas. Perhaps the trial resources were getting stretched too thin.

Another possibility raised by James Cavuoto
, Editor and Publisher of NBR, is that the FDA is too darn stringent in what it considers a treatment response:
Unfortunately, much of the progress in our understanding of DBS mechanisms in depression is potentially wasted without a vibrant installed base of patients and clinicians using and perfecting DBS therapies. ... In our view, the FDA needs to understand the vital importance of getting first-generation devices into the field and move away from arbitrary standards like improving symptoms by 50 percent in 50 percent of the population. The notion that if we can’t help everybody we shouldn’t help anybody has no place in medical science, particularly when you consider that neuromodulation therapies are working with the hardest-case patients who have not responded to other therapies.

Finally, there is the unfortunate possibility that DBS treatment in this patient group doesn't work as well as initially thought...

If anyone has additional information, please leave a comment.


1 This blog [EDIT:  i.e., the DBS Trial blog] is written by an individual who for the past four years has had an implanted device for the treatment of intractible depression.


Johansen-Berg H, Gutman DA, Behrens TE, Matthews PM, Rushworth MF, Katz E, Lozano AM, Mayberg HS. (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex. 18:1374-83.

Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45:651-60.

Further Reading:

A Depression Switch?

The Sad Cingulate

Sad Cingulate on 60 Minutes and in Rats

...But My Subgenual Cingulate Is Sad

Deep Brain Stimulation for Bipolar Depression

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At January 19, 2014 7:48 AM, Anonymous Anonymous said...

Disappointing. I watched Dallas Buyers Club recently about the early stages of the HIV crisis and the development of HIV drugs (from the point of view of the patient, mostly). I'm wondering if something similar will happen in the DBS field, with some people starting to hack their own DBS systems to try things out by themselves, and in the process make faster progress.

At January 20, 2014 4:41 PM, Anonymous Anonymous said...

Psychiatrists can't even agree on what "major depression" is (and isn't. So this is not surprising.

At January 23, 2014 2:28 AM, Anonymous Anonymous said...

Neurocritic, after reading Footnote 1 I was wondering if, anecdotally, the DBS treatment seems to be working for you. Anything you would like to share? Any side effects? Any changes in effectiveness over the 4 years? Thanks.

At January 23, 2014 9:23 AM, Blogger The Neurocritic said...

Oh, I was referring to the DBS Trial blog... The writer there says, "I have been implanted with an EXPERIMENTAL electronic stimulation device - in my BRAIN - to reduce my depression. I've crossed the four year mark."

At February 05, 2014 6:55 AM, Anonymous Anonymous said...

As part of the Broaden Study, I can state that the side effects caused by the device were, at times, worse than the depression itself.

Those that conducted this study and anyone else who has jumped on the DBS bandwagon would do well to take a good hard look at those left in the wake of this failed study.

At March 14, 2014 1:44 AM, Anonymous Anonymous said...

I'm so curious to know more about this study and anything to do with the brain and its relation to all forms of mental illness. I was always skeptical about narrowing down something as complex as a mental illness to one "hotspot" in the brain but I recall the Lozano presentation on DBS for depression and the research indicated several areas had noticeably decreased activity while cg25 had high activity, so I followed along. I also recall a statement made by Mayberg herself, a couple actually; "for all we knew, we could turn on the contacts and make things worse" which pertains to your comment a great degree. She also noted that for those it doesn't work for, that, "they perhaps aren't the right patient" and that "we would have to understand the biology better". Which again is why I say I'm ever skeptical of narrowing it down to one thing, or place in the brain or structure. But I can't help but pervay upon the empirical facts we do have and think that perhaps we need do need to change how we rate and consider treatments as is stated in the Red lettered text. I should also state that I'm not so much a neuroskeptic rather, I'm near entirely neurocentric. I didn't come here to change minds or to upset but as the nature of good debate goes, to better approximate the truth. As my opinion stands I believe wonderful answers can be found within the brain but we must know more understand better. In the journey of 100 miles we've went about three inches and even those three inches have come from horrible mistakes. I assume most people here have heard of a patient by the name of H.M. who had his entire Hippocampus removed and could no longer translate recent events and information into lasting memory but his motor function memory was intact. Or consider Alzheimer's disease, a disease where one not only forgets but cannot comprehend the very nature of food, the concept of eating, where they are in time and space and we know that that is without a doubt do to neural malfunction and degeneration. Alzheimer's patients often suffer from depression and personality changes, aggression and isolation. So I believe the answers are primarily between our ears and that we shouldn't give up on the most complex thing in the entire universe.

At April 18, 2014 5:05 PM, Blogger anonymous said...


At April 20, 2014 1:59 PM, Blogger The Neurocritic said...

Anonymous of April 18, 2014 - I'm sorry that you and the earlier Anonymous of February 05, 2014 had such a terrible time. Your experience in particular sounds like medical malpractice.

At April 28, 2014 11:10 AM, Blogger anonymous said...

I agree with you in thinking this may be medical malpractice. I had to go home with my sister and she took care of me for 17 days because I couldn't function. When she found a good rehab facility, they wouldn't let me go. So I had no Rehab. I couldn't walk or talk right. I couldn't use my debit card or cell phone and I was still hallucinating. I am thinking of having a free consultation with an attorney.

At April 28, 2014 11:13 AM, Blogger anonymous said...

I have been thinking that this may be medical malpractice for a while. I had to go home with my sister and she took care of me for 17 days. I couldn't walk or talk right. I couldn't use my cell phone or debit card, and i was still hallucinating.
They said they would help with rehab, but when my sister found a facility for me to go to, they denied it. I am thinking of getting a free consultation with an attorney.

At May 01, 2014 11:09 AM, Anonymous Anonymous said...

I can't believe they didn't MRI the patients prior to surgery. (Is that accurate?)
I have had DBS for OCD and they used an MRI to place the electrodes accurately. This is absolutely standard in DBS treatment.

At May 01, 2014 11:33 AM, Blogger The Neurocritic said...

This press release, Precise brain mapping can improve response to deep brain stimulation in depression, describes a new paper from Emory, Case Western, and Dartmouth:

Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression, published in Biological Psychiatry.

"Results: Whole brain activation volume tractography (AVT) demonstrated that all DBS responders at six months (n=6) and 2 years (n=12) shared bilateral pathways from their activation volumes to (1) medial frontal cortex via forceps minor and uncinate fasciculus, (2) rostral and dorsal cingulate cortex via the cingulum bundle, and (3) subcortical nuclei. Non-responders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from non-responders."

At May 01, 2014 11:37 AM, Blogger The Neurocritic said...

Anonymous of May 01, 2014 11:09 AM - I believe that is the case, or at least this sort of probabilistic tractography was not done.

At July 20, 2014 6:34 PM, Anonymous mcan said...

I am part of the study. It DID work for me and MRI mapping was done prior and following my DBS surgery. The abject misery of severe, treatment resistant depression necessitates the need for vigorous, ongoing research in this area. Depression is a DEADLY disease and should be treated just as seriously as any other "physical" malady. Yes, there area always risks associated with groundbreaking medical treatments, but the rewards for those of us who suffer (as well as our loved ones) are immeasurable. Would we have the same objections to those who pioneer experimental treatments for cancer?

At July 20, 2014 6:50 PM, Blogger The Neurocritic said...

mcan - I'm happy to hear that the treatment worked for you. Thanks for letting us know. I wish you continued good health.

At August 12, 2014 3:40 PM, Anonymous Anonymous said...

Clearly the accuracy of electrode placement is key and the way in which this is achieved for Parkinson's disease is to do the electrode implantation by real-time MRI. With an MRI-compatible neuro-navigation device, the accuracy of placement is within 1 mm. I would never do an electrode placement any other way, and perhaps the variability in outcome is more attributable to outmoded placement technology than anything else.

At September 08, 2014 8:24 AM, Anonymous Anonymous said...

My wife is a participant of the Emory-Mayberg trial, implanted in 2011 (fMRI for analysis, MRI used for placement). For us, this has been a life changing event. After many years of frequent medicine changes, ECT, phsychotherapy, etc., all of which worked only briefly, my wife was at a point where her brain was non-functional: Speech was difficult, driving was impossible, relationships were unimportant, my wife was just a shell of the incredible person she once was. Then the implantation and the slow but steady return to life. After three years with DBS, the improvements continue, getting better with each passing month. I am not sure whether the connections in the brain continue to improve or whether my wife is able to work on the physchological issues now that the biological issues are greatly improved. Either way, my wife has her life back and she is immeasurably grateful for this technology and the trial at Emory.

Side Effects: None

Wishes: A rechargeable IPG. Currently, batteries last about 11 months and require (minor) surgery to replace.

A side note: I have always found it amazing that the public assumes that the brain is the only perfect organ. Other organs can be defective, but not the brain. Everyone agrees that Diabetes and Cystic Fibrosis have a biological cause, but it is controversial to say "mental illness" has a biological cause. The Emory DBS trial proves to me that there is indeed a significant biological component to depression.

At September 09, 2014 1:38 PM, Blogger The Neurocritic said...

Thanks for reporting on your wife's condition. I'm glad to hear that DBS has been so successful for her. I wish her continued good health.

At October 26, 2014 12:36 PM, Anonymous Anonymous said...

I am part of the Broaden Study and am in the 4 year follow up phase. I go in for a 6 month check in a few weeks. I'm definitely going to try to get more information about the study and what happens if they abandon this part or when it is over. The paperwork said they would turn it off or take it out at the end of the 4 year study. But in my opinion it has helped me. Yes, I have been hospitalized several times after the procedure but I am functioning much better than I was prior to the study. The objective measures may not show it but I know it has helped even just the slightest. I'll take that.
But I'm worried about the "what next." Have you heard of any updates since earlier this year?

At January 28, 2015 1:06 PM, Anonymous Anonymous said...

I was one of the first people to have this treatment in Chicago maybe 6 or 7 years ago. Here's the scoop. We think that only people with depression does it help. Nothing else. No personality disorders, no eating disorders, no bipolar, no medical conditions or drugs which cause depression. Further, the other sites did not require bilateral ECT as a requirement. This site did. The people who had that would have already been pre-screened to have had severe depression. In the other sites, we think the candidates were so desperate they answered questions to get into the study. So bipolar would become straight depression. Seasonal affective, straight depression. You get the idea. So this treatment only works with one type of depression and one type alone.

For side effects, I have had none. It has continued to work for me. The quality of neurosurgeon determines this one IMO. A few millimeters off and you have misery with no benefits.

At January 28, 2015 1:12 PM, Anonymous Anonymous said...

PS. I am out of the 4 year windows in 2011 and they will keep it going for as long as you wish. Don't worry about that. You just don't have to go in for testing.

At January 28, 2015 3:14 PM, Blogger The Neurocritic said...

Thanks for sharing your positive experience with DBS. I'm so glad it worked for you. It's also good to know about the more restrictive inclusion criteria that may not have been enforced elsewhere.

At January 29, 2015 1:01 PM, Anonymous Anonymous said...

my wife had this surgery as part of the St Judes trial and it was the worst decision out. No follow up, lack of understanding and in my mind, incompetence. She now has major cognitive issues and memory loss which has been proven to be a result of excessive stimulation. Any adjustments to the device stimulation settings need to be carried out strictly in a controlled environment where someone can be monitored over a period of a day or two to guage any conflict, not in a half hour session with a clinical nurse who doesnt have the experience specific to depression. Other problems are that because it was a clinical trial, any ability to get open communication from the study are cloaked in darkness. Companies need to remember they are dealing with real people with families. Your experimental brain surgery needs to be radically slowed down rather then rushing in to try to capitalise in on a multi billion dollar industry.

At January 29, 2015 8:43 PM, Blogger The Neurocritic said...

I'm sorry your wife had such a negative experience. Seems there's such a huge degree of variability at the different sites, and of course in how individual people respond to treatment.

At January 29, 2015 10:58 PM, Anonymous Anonymous said...

I think I lucked out with the surgeon. He does his surgery differently than everyone else. Uses sound of neurons in the brain to navigate. No other surgeon does that. Different regions of the brain make different characteristic sounds.
As for keeping it after the study has been cancelled, I'd say that is slim to none. I misspoke earlier. From everything I understand, according to US law, a patient CANNOT continue receiving treatment for a non-approved therapy. This happened with Vagal Nerve Stimulators. Patients had theirs removed. So all people in the study would have the units partially or wholly removed and go back to previous treatments. It is still property of ANS. You can apply for Compassionate Care and slim chance keep it going but then would need to fund the surgery and equipment out of pocket. I doubt anyone would have the spare 120k lying around each year for that. As for the future, I question that any company will spend the 70 million again on already failed FDA treatment.

At January 30, 2015 11:01 AM, Anonymous Anonymous said...

Ugh. There is so much misinformation floating around, if I had a nickel for each...
First off, patients were told you could get better, worse, stay the same, or you could die. It's brain surgery. It's not a treatment, it's an experiment. Nobody should have signed up without expecting possible severe side effects. This is a last ditch treatment for patients who have failed ECT, failed drugs, failed everything and were likely to stop eating, starve, or attempt suicide. ECT causes severe memory loss and cognitive side effects by the way.

Second, the information that it failed FDA approval or halted by the FDA is prima facie a blatant lie and demonstratively false. St Jude, the company, withdrew the trial. They are working to identify better patient criteria selection to ensure people who go through this treatment are likely to reap benefits. This is not a one size fits all treatment. Post partum depression, bipolar, even one manic episode, and you would want to wait and enroll in a study that fits your diagnosis. There will be deep brain studies for bipolar patients and others. It's like there are different strains of the flu.

Third, any current study participant will continue to get treatment even after they are finished with the study. St jude will continue to donate the Libra devices for battery replacement.

Forth, regarding adverse effects. People with high blood pressure, smokers, drug users, anatomical or structural abnormalities should think carefully and weigh their options before rushing in to this treatment. It is major surgery and you are statistically likely to encounter more problems. You might be a poor candidate for such an invasive procedure.

Last, understand this is a temporary mechanical stop gap to relieve symptoms, a salvage operation to rescue treatment resistant, endogenous unipolar depression patients otherwise doomed to a life of misery, until something better comes along, such as gene therapy.

At February 01, 2015 6:00 PM, Blogger The Neurocritic said...

Anonymous of January 30, 2015 11:01 AM - The reason there may be so much "misinformation" floating around is that the sponsors of the trial haven't released any information to the public. And even some of the patients might not be fully informed. This raises all sorts of ethical issues.

I have not found any info anywhere that explains why the BROADEN trial was halted, other than in the Neurotech Business Report, which said the news was delivered at the 2013 NANS meeting. Only experts and professionals in the field of neuromodulation would attend that meeting.

The original BROADEN trial website has vanished into thin air. But you can still find remnants at For example, this page lists three centers and the participating psychiatrists in Chicago, Dallas, and New York. Here we have the clinical study overview, FAQ and brief version of the inclusion criteria.

But SMJ has only this to say about the BROADEN trial: "This study has been closed and is no longer enrolling participants." And I couldn't find anything on either.

So if you know of a source of public information, please let us know.

At February 01, 2015 6:06 PM, Blogger The Neurocritic said...

Here is the correct archive link for the BROADEN clinical study centers (and participating psychiatrists) in Chicago, Dallas, and New York.

At February 03, 2015 10:43 AM, Anonymous Jim Ingham said...

Hi, has anyone tried "cranial electrical stimulation"? It is easier to administer, can be done at home, and is noninvasive. Lot of information on the Internet about it so Google it.

At February 05, 2015 6:08 AM, Blogger 278-005 said...

I haven't taken the time to update my personal blog, partially due to the changes in the study and other personal reasons. But I will soon.

From what I have inferred about the "failure" is that some specific sites (like the original 3) would pass the FDA criteria but as it was rolled out, the successes diminished. My personal opinion, with no data to back it up, is there was a combination of things that occurred, many of them already mentioned. The 'perfect' candidates for the study may not have been screened as effectively at the new sites. The placement of the nodes may not have been as precise. And the biological fact that my brain is not your brain because no 2 brains are identical, played a large role.

What 'they' have learned is enormous. I truly have empathy for those in the study who had adverse side effects. Possibly more could have been done to avoid those. One person with whom I have some contact with, that had severe problems, agrees that the technology has promise and doesn't want the research to cease, but wants more evidence based controls in place.

From reading/listening/studying Dr. Mayberg and others' research, it is very apparent the technological advancement DURING the study was exponential. Fine tuning the ability to actually "map" an individual's depression is right around the corner. Without the successes and failures of the studies, this would not have been possible.

Are there ethical concerns? Yes. And there were when the first HIV medicines came out... and first heart transplants... and and and.

Again my guess, not fact, is that the research will divide the disease 'depression' into a number of similar diseases, each with it's separate "best" treatment options.

As for the future of those in the St. Jude study, the paperwork has already been approved (through FDA humanitarian exemption) for some of us who wish to keep the units and will be replaced with the smaller, rechargeable Brio device. (I say some, not all, because I can only speak for myself and the few I have contact with). (There is a closed FB page some of us gather on).

I do believe some of the protocols should have been more stringent to avoid further hurting those with bad side effects. But I also believe 'they' continue to gather data on those not out of the four year study and the results will change depression treatments and deep brain stimulation, for the good.

To answer Anonymous from Jan 23 of 2014, I have intentionally not spelled out my results so that I not taint anyone's decision to have the procedure or to cause placebo side effects by talking about my side effects. But yes to both questions. It is working for me, including the new rechargeable but also yes, I do have some side effects. In my case, luckily, the side effects are manageable.

**I have to laugh - in order to post this comment, one must do something to keep spammers out and also, in their words "prove you're not a robot". Nope, not one yet, anyway.

At February 11, 2015 9:20 PM, Anonymous Anonymous said...

I had the St.Jude implant 1/7/2013. I seem to be improving VERY slowly month by month.I hope to actually try working a little soon.
I Recently had the 1st. battery replaced.
No side effects, except for the "tether" wire from new battery being a little too short and causing some mild discomfort in my neck at times.
I continue to have memory problems- perhaps due to bipolar ECT? and often experience "mental paralysis" when I try to do office work or think of calling people. I'm SLOWLY getting better at that - this comment is a positive step.

Thanks to all of the great people that have taken the time to put out the info!!

I have read the blogs from time to time and it has helped me.I felt bad that I couldn't contribute.
I hope that they continue to perfect this treatment.

At March 07, 2015 9:22 PM, Anonymous Anonymous said...

I had my surgery in Chicago on March 12, 2009. I went through a rigorous screening process, had an amazing surgeon, very thorough follow up appointments, and to call the results a miracle for me would not be an exaggeration. I tried just about every medication out there, countless hours of therapy, hospitalizations, and many series of shock treatments which did little more than erase years of memories. I have had no real side effects and feel incredibly blessed to have a life now. I feel really bad reading of the people who have had such different experiences than I have. I am so sorry. I feel like I have a second chance at life and am very very grateful to Dr. Mayberg and the amazing team I worked with at Alexian Brothers.

At March 10, 2015 10:56 PM, Anonymous Anonymous said...

Regarding Anonymous' comment on January 30, 2015 11:01 AM, as follows in part:
"Second, the information that it failed FDA approval or halted by the FDA is prima facie a blatant lie and demonstratively false. St Jude, the company, withdrew the trial."

Much of this confusion could be cleared up if the study sponsors practiced more transparency.
A bit of research reveals that St. Judes' BROADEN study was discontinued after the results of a futility analysis predicted the probability of a successful study outcome to be no greater than 17.2%. (According to a letter from St. Jude)

Medtronic hasn't fared any better. Like the BROADEN study, Medtronics' VC DBS study was discontinued owing to inefficacy based on futility Analysis.

If the FDA allowed St. Jude to save face with its shareholders and withdraw the trial rather than have the FDA take official action, that's asserting semantics over substance.

If you would like to read more about the shortcomings of these major studies, please read (at least):
Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes,
Takashi Morishita & Sarah M. Fayad &
Masa-aki Higuchi & Kelsey A. Nestor & Kelly D. Foote
The American Society for Experimental NeuroTherapeutics, Inc. 2014
DOI 10.1007/s13311-014-0282-1


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