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Interviewer: You've already tried mood-balancing medications such as SSRIs and cognitive behavioral therapy to treat obsessive-compulsive disorder or major depressive disorder, and those treatments aren't working. You're not alone. Treatment-resistant OCD and depression isn't uncommon.

Matter of fact, it's estimated 40% to 50% of OCD patients are considered treatment resistant. And when those first-line treatments don't work, many explore surgical options.

Dr. Ben Shofty is a neurosurgeon from the Clinical Neurosciences Center at the University of Utah Health and is an expert in surgical treatments for OCD and MDD.

And today, we're going to learn about common surgical treatment options that are providing hope to those with treatment-resistant OCD and depression.

Dr. Shofty, how long does a patient need to be on standard treatments until they're considered treatment resistant?

Dr. Shofty: For a patient to be even considered for therapy, they have to have availed all other therapeutic options, especially the non-invasive ones, which mainly consist of drug therapies, SSRIs, SNRIs, and tricyclic antidepressants, and behavioral therapies like psychotherapy, exposure and response prevention, and cognitive behavioral therapies.

Interviewer: And how long does somebody have to be on the non-invasive types of treatments before they can be considered nonresponsive? Is that a year or longer than that?

Dr. Shofty: Usually, we are looking at patients that have been suffering from the disease at least five years.

Interviewer: Before we head to some of the specifics about the three different treatments, some common questions that might come to mind when treating OCD and MDD with surgical procedures. First of all, in general, are the treatments effective?

Dr. Shofty: The treatments are super effective. Considering the fact that these patients are usually patients that have failed everything else, I think the treatments are life-changing.

Surgical treatment for OCD has been approved by the FDA for more than 10 years, and recently we had a lot of good high-quality data from around the world, in the United States, Europe, and even Australia, that show about 60% to 70% of patients respond to treatment and their disease improves by roughly 40% to 50%, which is a huge change. I mean, these patients can actually go back to living a relatively normal life.

Interviewer: So, I hear those numbers, and in the real world, that is a significant difference.

Dr. Shofty: That's a huge difference, yeah. That's a life-changing difference. Even some of the patients that we do not classify as responders because they only had 30% improvement in their disease metrics, this is a huge improvement even if they're not officially defined as responders.

Interviewer: And surgery can be kind of scary. Do you find that the patients that come in tend to be a little apprehensive about getting surgery for their condition or are they at a point where not so much because they're just looking for any sort of help?

Dr. Shofty: These patients are usually desperate. I mean, they've exhausted every other therapeutic option out there, including a lot of well-based therapies and some experimental therapies, and this is pretty much their last resort.

I also think over the last 10 to 15 years, there has been such a technological improvement in our ability to perform these surgeries safely. And these are quality-of-life surgeries, right? We're trying to improve these patients' quality of life.

So, these are super safe surgeries. Usually, there's a day of recovery inside the hospital, and then the patients go home the following day and go back to their normal lives pretty soon after the surgery.

Interviewer: Then after the procedures, and I realize that for each one it might differ and for each person it probably differs as well, but how long until patients start kind of seeing results?

Dr. Shofty: These are chronic diseases. Patients have been living with them for many years, usually anywhere between 5 and 30, and it takes time for the effect to sort of fully manifest itself. We don't talk about success of therapy at least until six months have gone by. Usually, the maximal effect is witnessed within a year.

Interviewer: When treating OCD and MDD with surgery, generally how do these surgical treatments work?

Dr. Shofty: Our main advancement and the main reason that these therapies are becoming so efficient these days is that we finally understood that it's not a single area of the brain that's not working well, but it's a network, which means that a few, two or maybe more, different areas of the brain are not talking to each other in the way that they should.

And once we've understood that, we can look into a specific patient's disease and the way his brain networks are sort of modulated or altered or working differently, and we can try and target that specific area and that specific place in the brain which is causing this miscommunication.

Once we do that, once we figure that out, the tool that we use doesn't really matter. I mean, we can choose from our sort of toolbox the perfect or the best treatment and sort of tailor the therapy to that individual patient.

Interviewer: That's incredible that you're able to trigger . . . you're able to pinpoint exactly where you need to go and what you need to do in each area.

Dr. Shofty: Yeah. And I think that's the main reason why these therapies are becoming better and better, because our ability to understand the specific patient and the specific patient's disease is becoming better.

Interviewer: And what are some other of the new developments that have allowed this treatment to be so successful?

Dr. Shofty: So, we have a bunch of tools that have become better and better over the last years. One of them is DBS, Deep Brain Stimulation, in which we have newer electrodes and newer devices that can provide smarter and more sophisticated stimulation to the area of the brain that we want to affect.

Interviewer: And Deep Brain Stimulation, I've heard of that before for other conditions.

Dr. Shofty: Yes, it's been around for almost 30 years. It's been used widely for movement disorders such as Parkinson's disease and essential tremor and others, and it's been FDA approved for OCD for more than 10 years.

Interviewer: So, Deep Brain Stimulation might be a procedure that would work for one particular patient. What are other options that are in your toolbox that might work for somebody else?

Dr. Shofty: One of them is creating a lesion or severing a specific bundle of fibers that sometimes causes severe OCD. We can do that today in a minimally invasive approach using laser fibers and under MRI guidance so we know exactly what we're burning and we are just damaging that specific fiber bundle inside the brain.

Interviewer: And with a tool like that, when you're damaging that specific fiber bundle, are there other side effects that might arise out of that?

Dr. Shofty: The reason that this approach was developed is to minimize the side effects, because you are only hitting the sort of damaged part of the brain that you want to affect. And when people used to do that 20 or 30 years ago, they didn't have all these sophisticated tools and they caused more damage than was probably needed. So, today we actually err on the safer side and do less damage.

And then if we have to enlarge the treatment, we can go back in and do it again. It's minimally invasive. Patients go home the next day. There are barely any incisions, so the recovery is super quick.

Interviewer: The third option is Vagus Nerve Stimulation or VNS. How does that work?

Dr. Shofty: So, VNS is an approved therapy for patients with the treatment-resistant depression. It is a peripheral neurostimulator. It connects to the vagus nerve, which then carries the electrical stimulation to the brain.

Interviewer: What is the biggest barrier or reason why somebody doesn't pursue a surgical treatment for their OCD or MDD?

Dr. Shofty: So, I think that there's a knowledge gap with our sort of community providers and community psychiatrists who are not always aware of the modern sort of surgeries and therapies that we can offer these patients. They're also not always aware of the recent advances and publications that have shown that these treatments are safe and highly effective for these specific patients.

Interviewer: Yeah. Somebody like you, this is all you pay attention to, so of course you would know about it.

Dr. Shofty: Yeah, exactly. I mean, medicine is so subspecialized today that it's hard to keep track with all the recent advances. But I think there are a lot of recent advances that have been published that show and support these approaches for these patients.

Interviewer: How should a patient bring this up with their primary physician that they're working with for their OCD or MDD if they're interested in a surgical option and it hasn't been offered?

Dr. Shofty: I think that if you've exhausted all other treatment options, you should bring it up just like that. "I've heard that there's a new psychiatric neurosurgery center at The U and I wanted to consult with them. Is there a chance you can refer me there?"

And we have a quick screening process that allows us to sort of say if the patient is a possible candidate. And for possible candidates, we have a very fast-track assessment process.

The second barrier is to be insurance. I think over the last four or five years, insurance companies have started understanding it's actually cost-effective to approve these surgeries for these patients. And Anthem has actually made a significant policy change and have added DBS for OCD as a medical necessity in their guidelines. So, I think it's easier today to get insurance approval for these procedures.

Interviewer: Well, I'd imagine that there's somebody listening that is very interested in a surgical option at this point given the success rate and given the change in somebody's life. Tell me a brief story as we wrap this up of somebody who came in, had the procedure, what they were like, and then . . . what their life was like, and then had the procedure, and then what their life was like after.

Dr. Shofty: So, we've had an OCD patient who was basically house-ridden for more than three years. Every time he needed to go out of his house and come back, it used to take anywhere between four and six hours going back from the front door to the living room because he had to do so many rituals and so many compulsions. We've operated on him successfully, and six months later, he's back to work. He still has OCD, but he manages it.

One of the good things about these therapies is that they allow patients to respond to medical treatment and to psychological treatments such as exposure and response prevention, which they did not respond to before surgery. So, it's not only the effect of surgery, but it's the effect that it enables them to respond to other types of therapies.

And a lot of our patients have a similar story. They just went back to living a normal life with the disease and not living just under the disease.

Interviewer: Systematic reviews or meta-analyses may be trickier to carry out than you think. But there's help out there. We'll talk about that next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. "The Science and Research Show" is on The Scope.

Interviewer: I'm talking with Melissa Rethlefsan and Mellanye Lackey from the Eccles Health Sciences Library at the University of Utah. Melissa and Mellanye you're putting a lot of efforts into improving the quality of systematic reviews. And that's a very particular type of research. First of all, can you tell me what systematic reviews are?

Melissa: A systematic review is a pre-specified methodology that looks at the literature to answer a very focused question, usually about patient care.

Interviewer: So can you give a certain example?

Melissa: So for example, usually it's a PICOT type of question with a patient intervention, comparison and outcome that a researcher might be looking to answer. So for example, it might be looking at teenagers who are depressed and whether or not SSRIs would be better than placebo or a different drug class in preventing the onset of further depression or suicide or some other outcomes that would be of interest to a researcher.

Interviewer: So it's really important that these studies are set up correctly. How can not taking some of those steps lead to issues in research reproducibility?

Melissa: If you do not have a librarian or someone who's extremely familiar with literature searching methods involved, then what you can produce is the systematic review that may answer the question, but that because it was not well documented, it can't be replicated. So people, we can go in and they can look at the systematic review and they can think that they're getting an unbiased answer. But then, when you look at the details of the study, you realize that you have no idea how the study was actually performed.

It's very similar to in a clinical trial that's not well reported. You might have no idea if the results that they're getting are actually true because you can't tell enough detail from the methods to be able to ascertain that for yourself.

Interviewer: Really, it starts with the very question that they decide to ask in the first place. What are some of the issues that come about in that arena and how can you address those?

Mellanye: Sure. One of the things we do as librarians is help make sure that people are asking questions that can be answered by literature that aren't too big or that aren't too narrow. And once they have a question that there's adequate literature to support studying that question and so we can do initial searches into the databases to identify gaps in the literature, to see if that study has already been done, if it needs to be updated, if it hasn't been done in a while. We can find if it has been done, was it done accurately? Was it done well? And if not, what areas they could . . . if they need to change their question slightly so as to carve out a unique area of research for themselves. We can help identify just the body of literature that addresses their question.

Interviewer: And how you do those studies, of course, is important too.

Mellanye: Absolutely. And so we as librarians encourage people to register their study in a protocol registry and this helps them ensure that they're going to be doing . . . that they've thought about as a research team, do they have the capacity to do the whole study? It makes them think about every single step of what they will do in their study and outline it and submit that to an international body that is open to anyone to read. And it just helps the researchers go through the entire process, think through the entire process before they actually get started.

Interviewer: So how does it do that? Does it prompt with certain questions or . . .

Mellanye: Definitely. It's a lengthy, not too lengthy, adequately lengthy set of questions that asks them to describe previous studies in their field, that asks them to describe their search strategy and describes their approach and anything that makes their contribution unique or any limitations that their study will have. And then it puts it out into the Internet, into the field for their peers to look at and they can comment on it. It also secures their place, so this says, it lets them set a flag, "Yes. We are doing this study, " helps them find out if anyone else has already started on that study and it prevents them from being scooped.

Interviewer: What is that registry called?

Mellanye: PROSPERO. P-R-O-S-P-E-R-O.

Interviewer: And do you feel like people are using that or is this something that's kind of new?

Melissa: I think people are using it. I think it is somewhat new. People don't have to publish a protocol in PROSPERO. A lot of times, people will also publish their protocols in a journal. And there is a specific type of systematic review called the Cochrane systematic review. And in order to do a Cochrane systematic review, you have to publish your protocol in the Cochrane database of systematic reviews prior to the publication of the full systematic review.

So I think it is something that's been around for a long time. I think what we often find, though, is the lower quality systematic reviews out there aren't doing that. And we're trying to really help elevate the quality of systematic reviews much in the same way that clinical trials are trying to do by pre-registering their trial protocols, by making sure that all of the inclusion and exclusion criteria are out there from the beginning, that they know the outcomes that they're going to be looking for so that people can't go back later and switch the outcomes or make up new outcomes or decide because they're an expert that they want to include a certain study that doesn't actually meet their eligibility criteria.

So it's a quality measure, people are definitely accepting of it. And registering your protocol is actually part of the PRISMA guidelines, which is a reporting guideline for systematic reviews. It stands for Preferred Reporting Items for Systematic Reviews and meta-analyses. And it was published in 2009, I believe. And since then, the incidence of protocol registration has gone up quite a bit. It is still not great, but it has gone up significantly.

Interviewer: And you just touched on reporting guidelines. Tell me a little bit more about that and what that involves and why it's useful.

Melissa: Sure. Well, reporting guidelines, there are hundreds of them out there these days. But for systematic reviews, there are two that are out there that are really well disseminated and used. PRISMA, which I already mentioned, and the other one is MOOSE.

Interviewer: Oh. So many acronyms.

Melissa: Meta-Analysis Of Observation of Studies in Epidemiology. But reporting guidelines are really there to guide a researcher through the process of what things are really key to the reporting process. When they're actually writing that final journal article, what has to be in there so that this study can be reproduced and understood by the reader? And for systematic reviews, research time and time and time again shows that people are just not reporting their systematic reviews in such a way that is actually reproducible. And this is one of the ways that I think that librarians are really key, is because we can really help increase the reproducibility of this specific type of methodology.

Interviewer: Well, Mellanye, we've quite a bit about another common pitfall, which is how to search through data.

Mellanye: [inaudible] has 25 million citations in it. And you don't want to ask a question, you don't want to have a search strategy that's so large, you get lots of irrelevant results and you bring up a lot of static. That can be a real burden on the research team to have to go through extra thousands of results. But you don't want to ask the search strategy in such a way that it misses very relevant results. So as librarians, we can work on the search strategies to make sure we get exactly the right amount, not too many, not few, just right.

Interviewer: So give me an example of a search that might give you the wrong . . . maybe not the wrong information, but not enough, or too much. Either one.

Mellanye: Sure. One of the searches that I have worked on before, the research team did their search strategy with just the term "developing countries" and they missed a lot of highly relevant research. When they did their search they got about 17,000 results. When I added my search strategy in, including country names, including directions to the database and then form field tags and only searching for specific words in certain fields, it's kind of technical, but it really improved the results that came back. And it brought back about 3,500 results, many of which were actually relevant and would have been missed by that group.

Interviewer: You know, we're kind of going through the beginning, through to the end. What sort of an end step that you can help with?

Melissa: I think the end step, really, is the production of that final manuscript. Here in our systematic reviews core team, we do require authorship on manuscripts. And that's so that we can actually control how our literature searches are being reported. Because there's a tendency if you're not an expert in that area that you might not know what things actually need to be reported in order to make a literature search reproducible. So that really is our final step.

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