Episode 50: A Multi-Mechanistic Approach to Treat Anxiety and Depression with Dr. Corey Schuler

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Anxiety and depression are widespread problems today, and while conventional pharmaceutical treatment can work well for some people, others get limited benefit from prescription drugs. Talk therapy is well-worn and powerfully healing practice for many people who experience anxiety and depression, but if individuals are suffering from underlying physiological conditions that can affect mood—conditions like chronic inflammation, micronutrient deficiencies, and thyroid dysfunction— they may not be able to get the full benefit from these therapies.

In these cases, patients might benefit by adding a functional medicine approach to their treatment plan. In today’s episode of New Frontiers in Functional Medicine, Dr. Fitzgerald talks with Dr. Corey Schuler about taking a functional approach to helping ease depression and anxiety.

In this podcast, you’ll hear:

• What tests Dr. Schuler uses to assess depression levels
• What lab tests Dr. Schuler runs on patients that present with anxiety and depression
• Why cortisol timing matters as much as a cortisol level when assessing the cortisol response
• Why running an inflammation panel is critical for patients with anxiety and depression
• Herbal supplement research showing data as effective as lorazepam and other benzodiazepines
• How to dose supplement and micronutrient support in tandem with SSRIs and SNRIs
• How high-dose fish oil may help with anxiety
• How slightly tweaking herb and supplement dosages can improve outcomes and ease side effects

Podcast Sponsor – Integrative Therapeutics

Everything they do at Integrative Therapeutics is focused on helping integrative medicine professionals cultivate healthy practices – from the development of science-based nutritional supplements, to innovative, actionable resources and professional insights that have the power to inspire and enrich you, your patients, & your practice.

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine, and today is no exception. I am thrilled to have Dr. Corey Schuler returning to talk to me. You remember him from the podcast on the elemental diet and they were really popular.

I know I got a lot of great, great feedback and Corey packed those podcasts with just really wonderful information. You can go back on to the podcast page if you haven’t listened to them, and download them, or check out the show notes. I’m sure you’ll enjoy them if you haven’t heard them. Today, we are going to be talking about anxiety and depression, another area that Corey has been working with clinically, and just applying that really great brain of his on to… but let me just give you a little bit about him, and then we’ll jump right into our topic.

Dr. Schuler is the director of Clinical Affairs for Integrative Therapeutics. He is a board certified medical affairs specialist, a certified nutrition specialist, licensed nutritionist, registered nurse and chiropractic physician board certified in clinical nutrition. He has a lot of initials after his name. Actually, you can check out his bio. He’s additionally earned degrees in phytotherapeutics and business administration, and has a private integrative practice in Wisconsin.

Dr. Schuler is adjunct assistant professor at the school of health sciences and education at New York Chiropractic College. He volunteers for the Board of Certification for Nutrition Specialists and he’s a member of the Institute for Functional Medicine and American College of Nutrition. Corey prides himself on communicating scientific information in the most palatable forms possible as a speaker and writer. Corey, you actually achieved that. He’s a chapter contributor to the Integrative Medical Nutrition Therapy and Disease Prevention and Treatment textbook. Dr. Schuler, welcome to New Frontiers.

Dr. Corey Schuler: Thanks for having me. I appreciate it.

Dr. Kara Fitzgerald: Absolutely. It’s great to have you back. Today, we’re going to talk about anxiety and depression which I would say are epidemic. I mean, a significant percentage of my patients present to my office with both of these as complaints. We see them alone. We see them presenting in our patients together. We often see them with other chronic conditions happening. First of all, talk to me about the underlying potential mechanisms in these conditions, and any comments on why the high incidence as you’re moving through these would be great.

Dr. Corey Schuler: Sure. In terms of splicing this out, there’s a number of reasons probably why we’re seeing anxiety and depression on the rise, and some of it has to do with lifestyle and environmental factors to be fair. That’s probably not what we’re going to get into as much if depression is caused by grieving, or loss, or if anxiety is caused by a traumatic event. What we’re going to be talking about today could probably be useful in some regard, but honestly that’s usually the territory of talk therapy, or neurofeedback, or psychiatric medicine, and that’s really not my space that you mention. I’m a nutrition guy, right?

Dr. Kara Fitzgerald: Right.

Dr. Corey Schuler: I’m a capital G generalist and integrative medicine person, so this isn’t … I treat it because it comes in. I treat it because I need to and I’m asked to help those individuals, but certainly not a specialty. I’m splitting it, right? I’m really talking about the biochemical factors as it relates to anxiety and depression. Why does it … I guess I can’t … I’m not the best person to speak to exactly the rise, but I mean, look around. We’re in a very stressful time in the world that’s sort of this precarious position that we all face on a daily basis just between traffic and lack of sleep and being on the internet all the time.

Dr. Kara Fitzgerald: Yeah, right.

Dr. Corey Schuler: It’s cause for concern, right? In terms of the underlying mechanisms, and I guess to add to my disclosure, I have to add that I’m a really simple person. I’ve gone to school a lot but when you shed it all away, I’m just like … I need to know nuts and bolts stuff in order to understand it for myself if I have to teach it. When I’m seeing patients come in with anxiety or depression. Right, there’s versions of that too. There’s major depression. There’s moderate depression. There’s mild depression, anxiety, generalized anxiety disorder, burnout.

Everything is a spectrum. If I had to make sense that I had to make it simple. I really created, and I didn’t create it right. I’m stealing from all the brilliant people who’ve done tons of research either in basic sciences or clinical sciences, and I just identified what I consider four pillars of the treatment of these overlapping conditions.

Dr. Kara Fitzgerald: Okay, perfect. Walk us through.

Dr. Corey Schuler: The first one I routinely call cortisol management, but you might want to refer to it as HPA-axis dysfunction depending on which literature you read. Elevated cortisol is one thing but there’s a timing of production of cortisol. Anyway, that’s a blanket statement about HPA-axis dysregulation. That’s my first pillar. I’ll name them all so we can follow along and then I’ll tell you about them, and then I’ll tell it to you again. The next one is probably the most popular one, and that’s just neurotransmitter signaling. Essentially almost all of our medications for anxiety and depression are based around this theory, and so it still creates a pillar.

Its contribution in where this all fits is probably less so than in conventional practice, but it still gets a pillar. The next one is I’m referring to as the thyroid area. The hypothalamic-pituitary-thyroid axis is another modifiable pillar that we can work with. Then the last one, which is the deepest of all holes, which I know that you’ve spent a lot of time interviewing experts on, is the component of inflammation. If I can sort through … If I can look at a person and work with them and hear their story, and evaluate labs or questionnaires, I could figure out which of those four are important for them, and which one can I maybe rule out a little bit, which ones do I have to pay less attention to, what’s already been tried, and this just gives me structure.

Dr. Kara Fitzgerald: I have to ask you, questionnaires you might be using, anyone you care to mention or is there a questionnaire we can share with our readers that might be useful, something you’re using in practice? Our readers, our listeners.

Dr. Corey Schuler: I have a handful. It’s like, choose your own adventure. The ones that are the oldest and used most in literature but require observation of the patient during the interaction are the Hamilton Scales. There’s a Hamilton Anxiety Rating Scale, and a Hamilton Depression Rating Scale. HAM-A and HAM-D. Those are useful, but you have to pay attention to the patient how they’re interacting with you, how they’re answering questions. They’re brief and they don’t take long to observe but those do require observation.

Oftentimes while interesting in research, they aren’t used that much in practice. Two of the ones that I prefer are just the patient health questionnaire or the PHQ9, and the Beck Depression Inventory. Beck Depression Inventory is a little bit bigger. It’s 20 plus questions and gets to a little bit more of really what’s happening for depression. Don’t let the name fool you. It definitely helps us understand someone’s anxious state as well.

Dr. Kara Fitzgerald: Okay. Perfect. Now, so you’ve done the intake. You’ve used these questionnaires. You’re thinking about the pillars concurrently. Do you want to talk to me about your next steps there? I mean, what kind of labs you’re using to assess the various pillars or just how are you putting your thinking together around this as far as assessment goes?

Dr. Corey Schuler: Sure. Actually, before I get to the pillars, I run a panel of, essentially what I would call standard-ish labs, labs that I can order from LabCorp, Quest, and things that might have already been run. Things like a thyroid panel. I don’t have to get as fancy with a thyroid panel, TSH, T4, T3, probably autoantibodies just to rule out Hashimoto’s. Those are going to help me lean towards, “Okay. Now, I need to pay attention to that thyroid pillar or for neurotransmitters.” I’m generally in a conventional lab. I’m not asking for a plasma level of serotonin, but what is helpful are things like methylmalonic acid or B12, or erythrocyte magnesium, erythrocyte zinc and homocysteine. Then I also run a ferritin iron panel to get me down the path of maybe there’s a micronutrient concern towards neurotransmitters.

Dr. Kara Fitzgerald: Yeah, perfect. You read my mind.

Dr. Corey Schuler: Cool.

Dr. Kara Fitzgerald: Anything else on your standard panel?

Dr. Corey Schuler: I do what I call the inflammation list, and so C-reactive protein. I also run Sed rate if they’re overweight. I look at vitamin D, fasting blood sugar, and hemoglobin A1C and if I’m feeling frisky, I’ll run a fasting insulin as well.

Dr. Kara Fitzgerald: Good. Okay. Keep going. Do you move into specialty tests or do you start with the information you got from that? Walk us through.

Dr. Corey Schuler: I think this is a bit of a chiropractic thing, but I’ll lean on it. Clarence Gonstead used to say, “Find it, fix it, and leave it alone.” If there’s anything to find on that panel, we start working on that almost immediately, so methylmalonic acid runs high like let’s do a nice bolus of B12. Anyway, that’s a subset step 1A. Once we get there, I do like moving into the functional test. I think urinary organic acids are lovely to provide some more detail on neurotransmitter metabolism and so there’s a handful of markers that we can look for that gives us clues at least to that.

Then I’m concurrently running … I prefer the dried urinary hormone assessments because I think that’s really useful. It’s a bit of a pattern. So a patient comes in and we’re like, “Well, we got your blood tests. Those are off and running, and now we’re going to do a couple urine tests.” There’s a nice rhythm to that. It takes a little bit longer to come back so often times I have to start treatment before I get those answers back.

Dr. Kara Fitzgerald: Can I just ask you, are you … You’re doing the dried urine assessment for sex hormones plus cortisol. Are you looking at the cortisol awakening response?

Dr. Corey Schuler: Yeah. That’s my baby. That’s what I’m really paying attention to, that first sample. I actually coach the patient pretty clearly on making sure that that first sample of … We’ll call it hormones, is done between 30 and 45 minutes post awakening. Oftentimes people like to use that first morning void and that is recommended in some cases. If they can be awake for 30 minutes or so before, that really gives me the best picture when cortisol should really be at its peak level.

Dr. Kara Fitzgerald: What labs are you using?

Dr. Corey Schuler: I just use DUTCH test, and the complete panel.

Dr. Kara Fitzgerald: Your organic acids? I know Dutch does have organics, but are you ordering above and beyond that. Any particular panel?

Dr. Corey Schuler: Yeah. there’s a handful that you get alongside of that, but I like using Genova for organic acids tests.

Dr. Kara Fitzgerald: Okay. All right. Perfect. Keep going on your journey with us on the pillars.

Dr. Corey Schuler: Yeah, absolutely. Once I have run off on those tests and I have to get somewhere pretty fast because in conventional treatment, a lot of the SSRIs or SNRIs take three weeks or so to work. Oftentimes the primary care doesn’t modulate those doses for six or eight weeks. If they’re on that path, it takes a year or more to figure out which medication works for them and why. Oftentimes if they’re seeing me and asking me for help, they’ve already been down that path.

I feel bad for them. This is awful. I don’t want you to suffer any longer. Is there anything that we can do to get things going in the right direction quickly? Luckily I have something that I really liked, and it’s a combination of adaptogenic botanicals. The one that I’ve grown to love is rhodiola. Rhodiola has evidence that shows improvement usually within about three days so you can know if you’re on the right track using rhodiola. There’s some dosing idiosyncrasies with rhodiola, but all in all, I love it. I use that in combination with ashwagandha and eleuthero.

Dr. Kara Fitzgerald: Okay. All right. Can you mention a product that you’re using, one of your go-to?

Dr. Corey Schuler: Yeah. The product I use is from Integrative Therapeutics is called HPA Adapt. It’s dosed at two capsules twice a day typically. Some people achieve benefit with just a single dose of two capsules a day, and some people could go a little bit higher if we needed to and that’s still within safe ranges of those herbs.

Dr. Kara Fitzgerald: All right. Perfect. Regardless of underlying ideology because you’re still on the journey in evaluation, you can start them on HPA Adapt, and you may expect to see some kind of favorable turnaround as little as three days?

Dr. Corey Schuler: Yeah. We should see some positive changes. Actually, we rerun those questionnaires that I ask, so I’ll do the Beck Depression Invention again at day three, five, and seven.

Dr. Kara Fitzgerald: Wow. Okay, good. Keep rolling through on your journey.

Dr. Corey Schuler: In context of the pillars, I put that one as … Well, there’s a lot of … Herbs do a lot of things and it’s neat because they have pleiotropic effects. There’s some effect probably to neurotransmitters signaling having ashwagandha in there probably has a pretty nice impact on thyroid function. There’s probably some impacts to HPA Axis regulation. Obviously, that’s the design of the product. I’m actually just empirically hitting three out of the four pillars. If they’re on a solid anti-inflammatory diet, and there’s nothing in their environment that’s outwardly inflammatory. We’re already on the path really well while waiting for those tests to come back.

Dr. Kara Fitzgerald: Good. I want to say it even though it goes without saying, you’re doing a full functional approach here. We’re zeroing in on specifics around anxiety and depression, but in your whole journey in working with an individual, you’re dialing in their diet and looking at food reactions, taking care of their gut and doing all of those pieces concurrently would you say?

Dr. Corey Schuler: Exactly.

Dr. Kara Fitzgerald: Okay.

Dr. Corey Schuler: That’s just part of the course. I can’t be a good nutritionist, and not pay attention to food intolerances and sensitivities. I can’t be a good nutritionist and have them have poor pancreatic function or bowel overgrowth. I just can’t do it. That’s getting done alongside of this as well, so sometimes it’s a fairly robust approach. I like to say it’s simple because it’s just four pillars, but like I said, that inflammation is a deep, deep hole.

Dr. Kara Fitzgerald: Yes, that’s right. I know. I appreciate that you’ve distilled it to four pillars and thinking about these specific conditions but that you’re doing that layer on a full functional approach. I’ve got a lot of questions for you. Do you want to continue to peel back your approach? I mean, I want to talk about at some point co-managing when somebody is on medication or what you might be doing differently. Do you have more to say on your approach, and then I can ping you on some more nitty-gritty questions?

Dr. Corey Schuler: I have a ton of research that I’d like to share. I can share that with you so you can just share it with everybody later because I do want to back up what I’m saying. However, in the interest of time and all of those important questions that you have coming, the one thing that I really want people to understand is that … I mentioned that I run C-reactive protein, and if they’re overweight, I run ESR. The challenge is … And it’s actually new and cool research, is that that can be misleading. In major depressive disorder, C-reactive protein is almost always elevated.

It would be uncommon to see that be in the normal range, and normal range medically is up to three. My range is a little bit tighter so I say it has to be less than one, but regardless that can be essentially negative. We can have a normal range for that and there could still be central inflammation. C-reactive protein is well-known to be stimulated by cytokines, produced in the liver and we know it’s a good marker for peripheral inflammation but to measure central inflammation, we really would need something like cerebral spinal fluid, TNF alpha.

I just don’t think somebody walking into my office is going to want to do a spinal tap to see if that’s positive. In those really significant disease states, like I said, we see it positive, but if somebody has moderate depression, or dysthymia, or burnout, it may be negative so don’t let that fool you clinicians is what I’m saying. You can either assume it’s there or just treat as if. We see super neat stuff. I don’t say it’s super neat practically, but from a research perspective we know things like cortical steroids can not only reduce inflammatory markers but can ease depression. We know NSAIDs have a lift effect. You can’t take naproxen sodium for the rest of your life to relieve depression but that’s useful information, right?

Dr. Kara Fitzgerald: Yeah.

Dr. Corey Schuler: I take that to say, all right even if it’s negative I still may treat the inflammatory response or dig further into that.

Dr. Kara Fitzgerald: You’re assuming inflammation is happening here?

Dr. Corey Schuler: I’m assuming …

Dr. Kara Fitzgerald: Even with your standard markers being within normal limits?

Dr. Corey Schuler: That’s what I’m saying.

Dr. Kara Fitzgerald: Do you think quinolinic acid on the Genova organic acids panel is useful at suggesting CNS inflammation?

Dr. Corey Schuler: Possibly. I would say likely. It’s one of those things that it’s like if I had any evidence I’m going to lean on it. If that’s abnormal then, “Yes, I’m going to do it.” There’s actually a really nice paper and it was written, or it was published in 2016. Kohler was the primary author on it and it’s just titled inflammation and depression, and the potential for anti-inflammatory treatment which really details all of this out, so I can make sure you have that. I think it’s a free article on PubMed, but that helps with this a lot. It’s like gluten sensitivity. If I have any suggestion that gluten is a problem, no matter which marker it is, we’re going to rely on that.

Dr. Kara Fitzgerald: Yeah. You’re doing a gluten elimination. Absolutely. It makes sense. You’re turning over all the biochemical metabolic stones and rooting out inflammation, and yeah, it makes sense. Keep going in whatever direction you want to in regards to treatment and then I’ll just ping you. You’ve talked about HPA Adapt which is a great product. What else might you be doing initially or once you’ve defined a pillar? Talk about some of your specific interventions.

Dr. Corey Schuler: Sure. When I have … Because, again, this leans on me being a simple minded person in some degree. Really the symptoms I’m paying closest attention to are really things like agitation, excessive worrying, restlessness because they both fit in the criteria of both anxiety and depression, and the nice thing about non-pharmacologic approaches is that I don’t have to choose sides. I can treat both almost simultaneously. The nice thing here is that when I split this down further, I have to think about the needs of the patient, and the needs of the patient … So patient preferences, are they having acute problems? Are they having spikes of anxiety or lows of depression that need to be treated on a PRN basis.

They happen on a periodic basis, but it’s not all the time. That’s one category that I have to pay attention to. Is it somebody who just … They’re on the verge of disability or maybe are disabled and they need an aggressive approach, and they need everything thrown at them that I can think of regardless of which ones is making the biggest difference. We can figure that out later. I also have that group that are at risk.

Quick story. The last patient that I had with anxiety, she had been working at the same place for 26 years. She has loyalty to the company but she got a new boss. It’s not going that well. She doesn’t really work well with the new coworkers, she’s overloaded. Now, that’s a person that I can’t take away her job stress. I can’t tell her to stay. I can’t tell her to find a new job. That’s not my role. It’s not my expertise, but what I can say is you’re really are at risk for developing one of these problems and needing pharmacotherapy.

Let’s put you in that bucket and treat you as an at-risk person. Then there’s just a fourth group. Then this is across many different aspects, but I call it the minimalist, somebody who doesn’t like to take a lot of things. They want to move into things slowly, maybe money is a concern and so they don’t want to take a lot of different products. That’s another group. That’s probably where I would start for by and large if they didn’t fit into those other buckets.

Dr. Kara Fitzgerald: Okay.

Dr. Corey Schuler: Okay?

Dr. Kara Fitzgerald: Yup.

Dr. Corey Schuler: As I mentioned, we … And I’ll tell you that one because now, I’ve let him do it. We’ve already started HPA Adapt, and I’ve started at two capsules daily. If they have a good response to that, if after three days in their first Beck Depression Inventory, they’re seeing signs of progress. That’s where we stay. That’s fine. Just two caps. That’s half the recommended dose. If they’re not seeing it within those three days, we increase it to two twice a day and the reason for that is because the one study on burnout that was published just in the last year on this particular rhodiola showed signs of that at 400 milligrams, so there’s 400 milligrams of it in four capsules.

In order to hit the evidence, you have to get to four a day. That’s part one. If they have elevated cortisol, trouble sleeping, trouble staying asleep, waking up groggy, I’m adding in Cortisol Manager, another Integrative Therapeutics product. That product also contains ashwagandha, so now I’m getting ashwagandha from HPA Adapt and Cortisol Manager and so now I’m really flexing on the thyroid and the ashwagandha effect. There was a nice study looking at subclinical hypothyroidism and ashwagandha at a fairly robust dose 600 milligrams per day. I’m getting both buttons so I can start that one right away as well.

Then the third product I pay attention to in this minimalist approach is a product called Lavela or WS 1265. In the literature it’s known as Silexan. If you go to PubMed and type in Silexan, you get a number of hits, and that’s the material that I’m talking about. For the minimalist approach, I just start at one soft gel a day but most of the time, I would start at two soft gels a day and I’ve written about why I like two soft gels a day better.

Dr. Kara Fitzgerald: Yes. In fact, we have a blog on that folks if you’re interested. You can track that down on our site and we’ll link to it in the show notes. Keep going, Corey.

Dr. Corey Schuler: Then I make sure that there’s an anti-inflammatory diet in place and if there’s not, or if we still think that there’s something going on, remember I said I assumed that there’s inflammation.

Dr. Kara Fitzgerald: There’s inflammation. Yeah.

Dr. Corey Schuler: I’m choosing either fish oil if they’re not taking it already. I’ll increase their dose if they’re already taking it or I’ll add in our colloidal curcumin product.

Dr. Kara Fitzgerald: I just want to add…if somebody comes back frankly hypothyroid or any of those micronutrients you’ve already evaluated for are abnormal, you may go beyond … I’m assuming you probably are considering thyroid hormone, and you’ve obviously got them on any of the micronutrients that they need. Is that correct?

Dr. Corey Schuler: That’s correct. The only caveat to that would be if they have subclinical thyroid markers but they don’t have many of the symptoms then I’m going to lean on treating that naturally. There’s pretty good evidence to say, let’s normalize the TSH if it’s outside of range and they’re having symptoms like constipation or significant fatigue. Now, you’ve got to tease that out. Is that fatigue coming from the anxiety depression? Is it coming from the thyroid? It’s not as easy as it sounds but the decision tree is pretty black and white on that. With symptoms, I’m recommending thyroid medication.

Dr. Kara Fitzgerald: Okay. Good. Otherwise if you’re just seeing a functionally abnormal thyroid, you might just go with ashwagandha?

Dr. Corey Schuler: Yes. That’s what I would do.

Dr. Kara Fitzgerald: Okay. Perfect. This is for somebody who … This is for the … I don’t want to take a lot of supplements individual. Incidentally, at any point in time, you’re going to just level them off where they are when they’ve turned around?

Dr. Corey Schuler: Yeah, ideally in any supplement … I mean, this is across the board. I always want them taking as little as possible. We’re always doing trials of discontinuation. My students get irritated by me saying that, “When did you start the trial of discontinuation?” “Oh, I haven’t started it yet.” Let’s start that. One of my favorite phrases, and I think it’s useful to … “The end goal isn’t to be on supplements, the end goal is to be healthy and live the life that you want to live.” So if you discontinue them that’s fantastic, but I have to get the effect that I want first.

Dr. Kara Fitzgerald: Yes, right. That’s a really good point. I appreciate you bringing that up. It’s easy to continue in the quagmire of too many supplements. I mean, I’ve fallen victim to that myself or I’ve actually instituted … I have patients who have been victims to that when I haven’t been attentive enough in the tapering process. Then let’s talk about when you need to turn the volume up or what are you doing acutely?

Dr. Corey Schuler: Acutely, I mean, these are rigorous recommendations so bare with me. In acute anxiety, because frankly acute anxiety happens a whole lot more than acute depression so I’ll just spend time on that. That’s when I love the high dose fish oil. I have no problem going the six gram or higher recommendations for EPA and DHA.

Dr. Kara Fitzgerald: Wow. Is that based on you reading the literature? Was there some kind of interesting study or studies that pinged you to do that? How did you start doing that?

Dr. Corey Schuler: There was a study in bipolar that I believe was 10 grams and I don’t have to go that high oftentimes, but it gave me enough confidence to use high doses.

Dr. Kara Fitzgerald: How long did they need to be on it before they saw a benefit?

Dr. Corey Schuler: Actually, we see relatively acute benefits. Sometimes people feel better within a few days. At least it takes the edge off, which is what I’m after. I’m not trying to fix acute anxiety and make it all better, I’m trying to make sure that it doesn’t get away from them.

Dr. Kara Fitzgerald: Okay. This is something that for people who have acute episodes of anxiety. Would you use it in panic disorder?

Dr. Corey Schuler: I think that’s reasonable place to use it.

Dr. Kara Fitzgerald: Okay. You’re going to maintain them on that daily dose, daily high dose, and then your expectation is that you’re going to see those really deep dips into significant anxiety leveled off?

Dr. Corey Schuler: That’s what I’m hoping for, yup.

Dr. Kara Fitzgerald: Okay.

Dr. Corey Schuler: We can check ourselves to know when we can discontinue or reduce that dose by just doing a red blood cell fatty acid analysis. Those are simple and inexpensive enough to get our head on straight.

Dr. Kara Fitzgerald: Right. You’re also doing all of the other functional work too so all of these together will give you some indication. What about when you’re working with somebody who’s chronic or really struggling with severe depression?

Dr. Corey Schuler: To be fair, this is really where the SSRIs shine. Major depression is definitely … We’ve seen benefit with that, with those medications. I’ll assume that they’re already taking it, which means I need to be a little bit more aware of which supplements I’m recommending. Things like the Silexan material, the Lavela product virtually has no interactions that we’re aware of. It’s really cleanly metabolized through cytochrome P450 pathways, not having any major interactions with at least the 5 major pathways. That’s something that I know that I can use, and if I need to be aggressive, that’s when I start those two soft gels daily.

Dr. Kara Fitzgerald: Okay. For somebody who’s being co-managed pharmaceutically, or with pharmaceuticals, you’re starting with Lavela?

Dr. Corey Schuler: Correct. The only time that I would be a little bit hesitant is it depends on the medication. This is where it all gets dicey. I’ll be really clear. If they’re taking an SSRI or an SNRI, I feel confident with Lavela. This material doesn’t have the same mechanism as a benzodiazepine. It doesn’t have the same mechanism of gabapentin or pregabalin, which is Lyrica. However, it has an influence on GABA, so if they’re taking one of those classes of medications, that might be, give me just a slight pause, but it’s not a stop.

Dr. Kara Fitzgerald: Okay. You might start them in a lower dose?

Dr. Corey Schuler: I might start at a lower dose or we might work with whoever their prescriber was for those medications to see can they be reducing their dose or work with them on … They need what they need right now or is it, can we work with something a little bit easier.

Dr. Kara Fitzgerald: Okay. Good. Are you using ashwagandha, rhodiola, some of these other go-to’s? Or do you consider those to be potentially contraindicated?

Dr. Corey Schuler: Yeah. The ashwagandha really doesn’t have much of a medication concern. Within those other adaptogenic herbs, the one that probably does have some actual pause would be rhodiola. There was a case that suspected that there was interaction between rhodiola and Escitalopram. I believe there was another one with Paroxetine. These are out of all the uses of these herbs and these medications. There appears to be two cases where people didn’t feel very well using … At least reported in the literature some SSRI and rhodiola interaction. That is something that I’m aware of. It’s not a full stop, but it’s a pause.

Dr. Kara Fitzgerald: Okay. If you’re going to use it, start really low, pay close attention. When you say they didn’t feel well, are you talking serotonin syndrome? What were their issues?

Dr. Corey Schuler: Yeah. I don’t think either one of them qualified as serotonin syndrome, but it was probably what you call a pre … I actually have it in front of me so I can mention it. It was tachyarrhythmia. A change in heart rate is probably the major concern, but they didn’t classify that as serotonin syndrome.

Dr. Kara Fitzgerald: Okay. All right. Worth paying attention to, and if you’re at all uncomfortable, start with Lavela.

Dr. Corey Schuler: Yes.

Dr. Kara Fitzgerald: If you’re working with an SSRI or SNRI. All right. Fabulous. This is extremely useful. What about actually tapering pharmaceuticals because that’s a huge goal of patients who come to my practice.

Dr. Corey Schuler: Yeah. I actually have to a little bit bow out of that question only because, number one, I recommend that it’s the prescriber that unprescribes it or tapers, and I also recommend that somebody who doesn’t have prescription rights not intervene with that, but the package inserts which I know that most people throw away or sometimes don’t even get are all available online through the FDA and so I would taper according to the package insert. There’s actually some … because they’ve done … There’s some literature and there’s some experience there in doing it but that is definitely an art that I would leave to the prescribing practitioner.

Dr. Kara Fitzgerald: Let me restate the question. I’m actually not suggesting that you yourself taper, but when a patient comes to you with the goal and they’ve got their prescribing physicians buy-in, how might you participate in that process with the interventions you’re using?

Dr. Corey Schuler: I guess we learned a little bit with this in the SSRI, in 5-HTP conversation that had been happening about starting a low dose of the supportive product, with the complimentary product and then tapering down maybe every one to three weeks by 50% or so which is aligned with the package insert, and while tapering down sometimes that complimentary product can be also increased. The rate at which it’s increased is really dependent upon the person’s tolerance.

Dr. Kara Fitzgerald: Right. Okay. Again, you’re doing all the concurrent work. Are you using 5-HTP much with your patients? We haven’t touched on it.

Dr. Corey Schuler: Pretty rarely as a standalone. Actually, there’s a selfish reason for that. They probably already tried it. I lose all credibility when I’m like, “Oh, I have this great thing. It’s called 5-HTP,” and they’re like, “You don’t think I’ve tried 5-HTP, and St. John’s Wort.” A handful of the more obvious ones, I’ve left it off the protocol. If I happen to come across somebody that actually has it, then there may be some times, especially if I have good organic acids data saying there’s insufficient serotonin production or excess metabolism that could be key.

Dr. Kara Fitzgerald: Okay. There may be a place for it, but I think these sound like these are the interventions that you’ve mentioned thus far  … The adaptogens certainly seem more root cause especially if you’re getting some evidence in the DUTCH panel or elsewhere. I know the research on Silexan is actually really pretty cool. I was looking at it not too long ago. Just mention to me some of the favorite standout studies. Not just Silexan aka Lavela but any of these things that we’re talking about.

Dr. Corey Schuler: It’s easy to talk about the Silexan studies because they’re awesome.

Dr. Kara Fitzgerald: Yeah, they are.

Dr. Corey Schuler: It’s pretty broad when a non-pharamaceutical gets compared directly to a standard of care medication.

Dr. Kara Fitzgerald: Many.

Dr. Corey Schuler: The first one was lorazepam so brand name Ativan .5 milligrams and compared to Silexan at 1 soft gel or 80 milligrams per day. Essentially over the course of the study, we saw fairly similar results without significant side effects of the benzodiazepine. That was the first cut at that, human clinical trial, placebo controlled, all the good stuff that you’re looking for in a research study. Then more recently, that same material was studied against paroxetine so brand name Paxil, at 20 milligrams.

This is a much larger study. This is 539 subjects. It was several arms. There was a placebo arm, a low dose Silexan arm, a higher dose Silexan arm and the paroxetine arm. We really got to understand the dose dependency of Silexan, and we also got to understand how it’s effective compared to pairing the two. Essentially what they answer is that Silexan higher dose had the best effect followed by the lower dose Silexan followed by the paroxetine, followed by placebo. It really outdid the standard.

Dr. Kara Fitzgerald: How about the time to benefit?

Dr. Corey Schuler: In the studies they were seeing, for sure, benefit within four weeks. The reality was that they were noting but not having great objective findings because objective findings are hard in this patient base. Within a week is usually the expectation of change. Some people report almost immediate change. Frankly, I think that might be product combined with placebo effect to have an immediate effect. The one thing that is really interesting and actually we refer to it as a side effect is eructation or burping out.

Dr. Kara Fitzgerald: Yes, that’s right. The lavender oil burp.

Dr. Corey Schuler: Yeah. I was actually speaking with some of the scientists in Germany this March, and I said, “Well, what about that? Is there something we can do with the soft gel? What can we do to help with that?” They said that might be part of the mechanism. We know from an aromatherapy perspective lavender, but a huge stimulation to all faction. As that happens, and it is transient. After a few days it goes away, but that might be part of why it starts to work pretty soon.

We don’t want that to go away. We want that to happen and so patients often will complain even if I told them it could happen. They say, “I don’t like it because I’m burping this lavender up all the time.” I say, “Well, the side effects of benzodiazepines are pretty vast, and the side effects for this material is that you burp out flowers, and I would take that any day.

Dr. Kara Fitzgerald: That’s right. I actually did have one patient complain about it. It’s just not a bad side effect. I thought it was funny that she complained. She got over it, needless to say.

Dr. Corey Schuler: I actually have a really patient … Sorry to tell this story.

Dr. Kara Fitzgerald: Keep going.

Dr. Corey Schuler: I love the campfire. I had a patient who I recommended. He runs his own business, and he started on two soft gels a day, had the burping effect, and after three days it was still there, and so he was really irritated by it. He’s like, “I’m taking it with food, and I took it at night just to try to mix it up and see if I could change it. It’s still there. Is there anything I could do?” We just dropped it back to one. We did the 80 milligrams and I said, “Let’s do that for three days.”

I would say mixing that transient effect of that eructation plus reducing the dose, he had no problems those three days and after those three days, he bounced back to the two soft gels a day and again had no problems. Sometimes it’s just tweaking that dose so slightly, and working with the patient to get where they need to go.

Dr. Kara Fitzgerald: Would you ever go above two gel caps or no?

Dr. Corey Schuler: We have practitioners that report going higher than that. If I lean on the studies, they’ve never gone higher than that in human clinical trials, so I tend to stay there, but I know that there’s really virtually no safety challenges with going higher.

Dr. Kara Fitzgerald: Okay. Good to know. I was just thinking about things that I’ve used acutely in practice. I love what you’ve presented so far. I think it’s pretty creative, and you’re getting good outcome and the rational is sound. We will link to all of the research studies that Dr. Schuler has mentioned. What about using GABA or Theanine, SAMe, some of those other nutraceuticals that are commonly used.

Dr. Corey Schuler: Yeah. In the acute protocol, I’ll call it, I do recommend oral GABA and I’ll go as high as about three grams a day.

Dr. Kara Fitzgerald: Oh, okay. High.

Dr. Corey Schuler: Yeah. That is high 750 twice a day or 750×2, 750 twice a day seems to have a good effect. I know there’s lot of questions about does GABA cross the blood brain barrier, blah, blah, blah. My report on that is I don’t care because people respond so what am I going to do?

Dr. Kara Fitzgerald: Maybe it’s metabolite. That’s the argument. I don’t know. Is there a secondary metabolite that does?

Dr. Corey Schuler: Yeah, a secondary metabolite. Is it a signaling system. We can nerd out all day on that but I don’t have an answer. I just know that people feel better, so that’s good. Then I also use robust doses of magnesium even if I don’t have the red blood cell magnesium. Either I didn’t run it or I don’t have it back yet. I’m going to just about bowel tolerance, if not getting to bowel tolerance with magnesium.

Dr. Kara Fitzgerald: What kind of dosages?

Dr. Corey Schuler: Probably in the eight to 1,200 milligrams is where most people see that bowel tolerance. I know some people go a little bit higher, but I don’t like to stay that high for that long. I also tend to use the magnesium potassium chelate and I have to be a little bit aware of medications that their on if they’re like … Sometimes there’s sneaky medications like spironolactone for acne, and a PCOS patient. Oh, shoot. That’s potassium sparing. I can’t give that, so then I move to magnesium glycinate and magnesium glycinate, I always have to go a little bit higher just because it is more bioavailable.

Dr. Kara Fitzgerald: You go a little bit higher or lower, you mean?

Dr. Corey Schuler: I actually go a little bit higher because I still want to reach bowel tolerance.

Dr. Kara Fitzgerald: Oh, okay. Got it. You’re looking at transit time with that. Okay. Perfect. What else do I want to ask you. You use magnesium glycinate. The potassium magnesium combination, what’s the counter-ion in those?

Dr. Corey Schuler: I need to ask somebody that knows.

Dr. Kara Fitzgerald: You don’t remember?

Dr. Corey Schuler: I don’t know

Dr. Kara Fitzgerald: Is it an Integrative Therapeutics product?

Dr. Corey Schuler: Yeah. It’s one of the krebs counter-ions so I’m going to say like I’m going to guess it’s a succinate or something like that.

Dr. Kara Fitzgerald: You don’t know.

Dr. Corey Schuler: I don’t know.

Dr. Kara Fitzgerald: If people are interested, they can just go over there and look at the product. The reason I asked you is because we’ve been talking about magnesium bioavailability and our clinical development program lately which has been pinging each other on it.  When I was writing the magnesium section in the laboratory evaluation’s textbook, at the time, there was really good research on aspartate. Actually, magnesium lactate which I never see, but those were the ones that came out so I was just curious about that.

All right. Let’s talk. I think we’ve covered a lot. It’s been really helpful. Just circling back to inflammation, you’re pretty versed on turmeric. I mean, you could use turmeric I think as an anti-depressive agent and somebody who’s really particularly inflamed. What do you think about that as an idea? Have you done that? Is there any research on it? Then I just want to ping you on how to determine quality turmeric.

Dr. Corey Schuler: Sure. I’ll lean on this story, and it’s recently published and it’s a secondary outcome but it’s got me super jazzed about it so I want to share it. Gary Small and his team at UCLA. Gary Small is a geriatric psychiatrist which typically means he’s looking at things like Alzheimer’s and Parkinson’s. He recruited for a study that looked at essentially non-Alzheimer’s dementia. He excluded those individuals with major depression.

They don’t have Alzheimer’s and they don’t have depression, and he studied turmeric, and just looking at things like memory and cognition, and then he also did some imaging studies because he’s a bit of an imaging guy. Not a bit. He’s very much an imaging guy. The last 18 months which is a pretty long duration study which is a failure oftentimes of most of our geriatric psychiatric type of studies. They’re usually not long enough because we think this is a lifelong disease, and so we have to try to … We have to do these longer studies but people are suffering so how do we shorten the time of the study.

Anyway 18 months is still long is what I’m saying. What he found was that even though they were excluded, people with depression, he saw depression scores go down. He actually used the Beck Depression Inventory to measure that. He thought that drop by about 41% is still …

Dr. Kara Fitzgerald: They weren’t clinically diagnosed but obviously they were mildly depressed.

Dr. Corey Schuler: Yeah. He went on to say that might actually be some of the benefit that we saw to the cognitive things. It doesn’t explain the improvements in imaging that we saw but it might … We know about Alzheimer’s and sundowning and putting people in a solarium every day is a really good idea getting them sun and lifting their mood that way is a benefit to their symptoms, but it doesn’t change anything with imaging. He saw changes in imaging as well so he’s like, “This is a partial explanation of why this could happen,” and actually maybe further research would go into more at least moderate or major depression and this dose.

Dr. Kara Fitzgerald: How did they measure memory? Do you know? Do you remember?

Dr. Corey Schuler: It was the Buschke Test, the Trail Making Test. I don’t think they did … For cognitive battery, I don’t think they did the clock-making one although that’s my favorite. I know the Trail Making Test was a primary indication of memory and cognition.

Dr. Kara Fitzgerald: Okay. They saw significant improvement?

Dr. Corey Schuler: They saw significant improvements.

Dr. Kara Fitzgerald: Geez, that’s really, really cool. What were they dosing and what were they using?

Dr. Corey Schuler: It was two capsules of theracurmin per day.

Dr. Kara Fitzgerald: Just two capsules.

Dr. Corey Schuler: That’s actually not even a high dose. In clinical practice, oftentimes we dose much higher than that. We might do 3X that dose for an inflammatory response. Whether our listeners have heard about theracurmin or not, theracurmin has this benefit of better bioavailability and all sorts of neat things in those terms. It’s not that it’s old news but now that we have an outcome of memory, cognition, depressive like symptoms, that’s neater. That doesn’t really matter to the person. I think I just said the word neater. Sorry about that.

Dr. Kara Fitzgerald: Yeah. You did. On a live podcast. It’s a modest amount, two caps a day.

Dr. Corey Schuler: Yeah. It’s easy.

Dr. Kara Fitzgerald: Bioavailability. I guess what I want to ping you about here is it’s been said that probably some of the metabolites from curcumin produced by the microbiome are significant to the action which would suggest that we want activity happening in the gut and not just full-on absorption of the curcumin. What are your thoughts there?

Dr. Corey Schuler: I have to share that there’s probably truth to that. That probably makes a difference. We know that curcumin realized on a glucoronidase to be active, so that’s happening in the gut. When we force turmeric or turmeric extract that has different curcuminoids in it, using certain synthetic drug delivery systems that may be problematic. There’s certain things that just open up tight junctions and allow things to go through, but they’re not very selective so other things go through as well. if you force things into the bloodstream, that’s a problem.

If you allow things into the bloodstream, that’s a different conversation. I think that’s really the conversation we’re having with Theracurmin. It’s finally milled. It’s water dispersible, and that’s what matters. That water dispersibility allows for some action in the GI system without forcing, It’s not breaking the door down into the bloodstream.

Dr. Kara Fitzgerald: Right. Got it. What are the other delivery systems that you’re concerned about? Can you mention them? I’m curious.

Dr. Corey Schuler: Anything with really long names. I don’t want to call anybody out in particular because there’s some really great also drug delivery systems, or nutrient delivery systems in curcumin, but there’s a handful. If they have a really long name or a proprietary name to it, sometimes there’s concerns about those delivery systems.

Dr. Kara Fitzgerald: Interesting. Then we’ll have to do the sleuthing ourselves. I can’t nail them down. Sorry folks.

Dr. Corey Schuler: Sorry. It’s my political answer, right?

Dr. Kara Fitzgerald: Good. Nice dance. Well, listen, Corey. As always, it was really terrific to talk to you. You just brought a lot of practical evidence-based information to the podcast today. I just know it’s going to be well received by clinicians, and just interested folks, so thank you.

Dr. Corey Schuler: Yeah. Thanks for having me. I hope some patients are benefited because this is really an unmet medical need and I think that sometimes us integrative practitioners feel a little bit overwhelmed with depression and anxiety, but we still have to help where we can so hopefully this structure helps a little bit.

Dr. Kara Fitzgerald: Absolutely. Thanks.

Dr. Corey Schuler: Thanks.

• Adulterants in turmeric: http://cms.herbalgram.org/BAP/pdf/BAP-BABs-Turmeric-CC-V6.pdf
• Inflammation in Depression and the Potential for Anti-Inflammatory Treatment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050394/
• A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. https://www.ncbi.nlm.nih.gov/pubmed/19962288
• Lavender oil preparation Silexan is effective in generalized anxiety disorder–a randomized, double-blind comparison to placebo and paroxetine. https://www.ncbi.nlm.nih.gov/pubmed/24456909
• Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms. https://www.ncbi.nlm.nih.gov/pubmed/28367055
• Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. https://www.ncbi.nlm.nih.gov/pubmed/28829155
• Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms–results of an open-label study. https://www.ncbi.nlm.nih.gov/pubmed/22228617
• The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms. https://www.ncbi.nlm.nih.gov/pubmed/26502953
• Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial. https://www.ncbi.nlm.nih.gov/pubmed/28219059
• Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. https://www.ncbi.nlm.nih.gov/pubmed/29246725
• Previous DrKF Dr. Corey Shuler podcast: https://www.drkarafitzgerald.com/tag/dr-corey-schuler/
• Beck depression inventory: https://beckinstitute.org/get-informed/tools-and-resources/professionals/patient-assessment-tools/
• http://go.integrativepro.com/stress-primer.html

 

Research:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050394/
• Inflammation in Depression and the Potential for Anti-Inflammatory Treatment
• DrKF FxMed Lavela blog: https://www.drkarafitzgerald.com/2018/10/02/oral-lavender-supplement-dosing-considerations/
• Trail making test: http://apps.usd.edu/coglab/schieber/psyc423/pdf/IowaTrailMaking.pdf