Antidepressants Explained: Benefits, Risks, and Alternatives for Depression | Dr. James Greenblatt

23:48We have to check a box, low thyroid. But then when we get out in training, we don't think, as mental health professionals, that it's thyroid. But thyroid's probably the most common that we see. But certainly, low testosterone and, you know, dysregulation of estrogen and progesterone can all contribute to depression. What I have found most helpful in my practice and the simplest is look at precursors to these hormones. And simple blood tests like pregnenolone and DHEA can often be low and really the simplest path to supporting all the hormones. Yeah.

24:30Dr. Mark Hyman:So doing a good hormonal assessment is key. Looking at thyroid, looking at cortisol, sex hormones, and it varies. I mean, even, you know, as older men, you can get low testosterone that can affect mood. Women have seen menopause, can have hormonal issues. PMS, all that can be related to mood issues, premenstrual dysphoric disorder. They're actually, they took Prozac and renamed it Seraphim and called it a drug for PMS, you know, which always made me laugh. But, you know, these things have to get looked at in depth. And the good news is there are ways to look at these things. There are ways to look at all those factors.

25:02Dr. Mark Hyman:And I think, you know, one of the biggest things affecting people is the insulin resistance and blood sugar issues. And they have to do with a lot of psychiatric problems, whether it's, you know, I've had people with panic attacks because of blood sugar swings or night sweats. But even more mood instability, depression can be a factor. So that's something easy to fix. And again, something often not looked at. Yeah, I mean, I think Chris Palmer's work and Georgia Ede and a number of other people have really kind of put this kind of understanding of insulin resistance as a factor in mood disorders and major psychiatric disorders and also as a treatment path.

25:39I think that many of our patients will get better on a kind of diet that's kind of supportive of higher protein and lower carbs. Sometimes it's hard to sustain ketogenic diet long term, but it's a powerful tool for mental health clinicians to support recovery. We've seen pretty dramatic changes.

26:03Dr. Mark Hyman:I know. It's powerful. Just those simple changes in diet and lifestyle make a huge difference. And so that's got to be the foundation of any mental health approach. So let's kind of dive into, you know, we've covered a lot of the issues from nutritional deficiencies to gut issues to inflammation causes to hormonal balances to genetic factors. All these are really important to assess. And one of you didn't talk about yet was toxins, which I think is also important. So maybe we can touch on toxins, then we can dive into the how do we diagnose the root causes through testing. Yeah, it is a frightening door to open.

26:37but we have to assess. I mean, I think in a standard psychiatric practice, the two most common things we see is mercury and copper, and both high and low copper. High copper usually is contributing to irritability associated with depression, and low copper, we see a lot in celiac or people supplementing too much with zinc, also has been a path to depression. But any of the kind of heavy metals can contribute to brain dysfunction. In kids, we see lead still. It's frightening. A lot of copper, a lot of mercury are the most common.

27:23Dr. Mark Hyman:I know. I mean, I haven't told the story, but I first got into functional medicine because I had mercury poisoning after living in China and eating a lot of fish and all this stuff. and I was so depressed. I mean, I knew I wasn't emotionally depressed. I knew I was physiologically depressed because I've always been a very happy person and I'm like, something's wrong and I don't need Prozac, which is basically what the doctors were telling me to do. And I'm like, no, there's something else. And I actually figured out that it was mercury. I chelated myself and it went away. So I think people don't realize that there's so many roads to roam depending on what your issue is.

27:58Dr. Mark Hyman:So the question is, how do you figure out what your particular issue is and how do we give people hope to help navigate this complex field? Because what I always say is tests don't guess, right? Tests don't guess. And that helps you guide precise treatment decisions, track your progress, see how you're doing. Tell us how you start, you know, thinking about the workup of someone diagnostically with depression and what are the kinds of diagnostic tests we should be looking at that we're not doing for mental illness. Yeah, no, it's really important. I just read an article, a group of people figuring out the DSM-6, the next version, when they commented on, we're still not ready to include biomarkers.

28:42So we're going to go 20 more years without a concept of biomarkers. And there's just 20, if not 100, that you and I know contribute to depression. But our colleagues who are kind of controlling this next manual for psychiatry are still way, way out of it. So, you know, the workup, again, has to include a history because stress and trauma just plays a role in everything. And we have to be sensitive to that history and family history because a lot of choice of supplements depend on family histories, even though the patient might not suffer if there's a family history of addiction and helps me fine-tune my treatment.

29:28But a basic nutritional workup, nutritional deficiencies, and that would include B vitamins and D and hormones and those precursors to hormones like pregnenolone and DHA. And then in a functional psychiatry practice, we like to add genetic testing, looking at MTHFR and a few other genes. We like to add looking at amino acid levels and fatty acid levels and a molecule called cryptopyrrole, which has tremendous implications. So it's a urine test. And so we try to have a comprehensive assessment, as we've been talking about for years, to be able to find that personalized treatment plant.

30:17Dr. Mark Hyman:Yeah, I think you're talking about things that we do all the time. We look at all the nutrient levels, homocysteine, melchromonic acid, which are B vitamin markers for B12, Foley, B6. And those really are important. You know, we look at zinc, we can look at red cell magnesium, we can look at, like you said, copper, even lithium levels in places like the hair, and they can be very helpful. And we look for heavy metals, we look for toxins, we look for change in the microbiome through stool testing, we can look for inflammatory levels in the body, we can look for insulin resistance through looking at lipids and blood sugar and insulin levels and A1C.

30:52Dr. Mark Hyman:So there's so many ways of looking at things. And we can also look at all the hormonal issues, complete thyroid testing and sex hormone testing and cortisol testing, or you mentioned pregnenolone. These are all things that should be standard part of practice, even gluten sensitivity, food sensitivities. These are real things that can drive mental health issues. And most doctors don't think about it. They don't know how to test it. They don't know how to order it. They don't know how to interpret it. And it's unfortunate. It's not their fault. They just don't learn about it because the orthodoxy hasn't accepted this yet.

31:21Dr. Mark Hyman:But I'm excited about kind of your book because it lays a lot of this out. And I think that for me, it's part of the reason that I co-founded Function Health, which was to empower people to get this data on themselves and not have to wait for some doctor to hopefully figure out that this is the problem and they can be going on for years. I mean, thyroid issues often go on for years or even a decade before they get diagnosed because people just don't think about it or they don't do right diagnostic tests. So I think that the test not guess message is really important. And now with Function Health for basically a dollar a day,$365 a year, you can get twice to your testing, see what's going on, and then you can modify those risks and change things.

32:04Dr. Mark Hyman:So I think it's really, really important. And the basic idea here is that depression and many mental illnesses are not just in your head, they're in your body. And you need to address those fundamental biological imbalances and test for those things and actually address those more systematically. So can you maybe share a little bit more about some cases and some stories of patients you've had that you've seen, you know, various factors, just to give people a flavor of how you work through some of these problems with patients? The challenge, I think, for clinicians is all the tests that we've talked about, you know, how do you prioritize and how do you understand, you know, what's part of that depression?

32:50You know, some of these abnormal tests might not be affecting the mood. So that's the challenge. And that's why, you know, it's important to see mental health professionals who know this work. But I think, you know, over the years, the cases, you know, that kind of most traumatic to me are when I can use words like remission and recovery. The mood is completely gone. So I've seen that in celiac disease, you know, from seven-year-olds to 40-year-olds, just completely eliminating gluten. I had someone in our training program presented a case last night of an autistic kid who was nonverbal, who just took lithium orotate, a nutritional supplement that I talk about in the book and we use all the time, and became verbal.

33:44So an autistic patient became verbal. and for our, you know, adults, the most common things we see are B12 deficiency. You mentioned homocysteine. I can't tell you how many patients that we've seen in the past year with these dramatically high homocysteine levels, which is a proven marker of deficiencies in B vitamins, B6, B12, and folate, and have also been shown, you know, for 20 years, a risk factor for depression as well as dementia. So it's a simple test where we then dig deeper to find out is it B6, B12, or folate, and then treat the underlying cause, and the depression completely disappears.

34:34Dr. Mark Hyman:You see these miraculous recoveries of things that are, quote, you know, chronic illnesses. And I think when you look at the biggest burden on our society, we talk about chronic illness and diabetes and so forth and all the cardiometabolic diseases, and those are big. But when you talk about disability, quality of life years lost, suffering, the economic impact globally, not the direct cost, but the indirect cost on society from people who are depressed and can't function, it far exceeds all the rest of that and most put together. So it's really one of the biggest drains on the whole society. And we have such a horrible mental health system that doesn't really address this, unfortunately.

35:17Dr. Mark Hyman:And, you know, you've been doing this for decades and so have I. And we've just seen over and over some of these repeatable patterns that aren't just voodoo or, you know, kind of made up. But if you look at the scientific literature, it's there. And if you put the pieces together, it's really there. and yet it just somehow hasn't gotten into traditional medicine and psychiatry. It's unfortunate. I wonder if you have a curiosity about why psychiatry is so resistant to this. Is it just so far outside the paradigm? It just seems like there's some areas where they kind of do this. Like they give Deplin, which is a very high-dose folate, or they'll give T3 for some patients with depression, which is a thyroid hormonal.

35:56Dr. Mark Hyman:They'll kind of play with the edges of it, but it's like they don't really even realize what they're doing. It's challenging and frustrating for me being, you know, kind of one foot in, one foot out. But I'm hopeful. I mean, last year, the American Psychiatric Association, you know, 10 ,000 psychiatrists, the theme of the conference was nutrition and lifestyle. So it's pretty dramatic. So there were a lot of lectures on nutritional psych and certainly lifestyle, sleep and exercise. So and then there's major psychopharm conferences. There's actually the Harvard Psychopharm Conference this year.

36:34There was a little section on nutritional psychiatry. So I think there were five of us that gave half-hour presentations. So things are changing, but not significant enough because the pharmaceutical hold is so powerful. And I think it empowers docs to think that they have a cure. And that's medicine is, right? surgery and drugs. I'm just hopeful that the younger generation of doctors and the limitations that's certainly hit with our just medication approach, that things have, I think, changed dramatically in the past two years and will continue to change.

37:17Dr. Mark Hyman:Well, let's talk about the medication issue because you write about that in your book and you talk about how these drugs are often difficult to get off of, and how they do, you know, once you get on them, you're kind of like in a pickle. One, because if you stop them, who knows if your depression is going to come back, and how do you prevent that? And two, you know, they're just hard to get off of because of the side effects of getting off of them. And so let's talk about antidepressants, and I think, you know, they seem to help some people, but talk about their efficacy or effectiveness over the broader population.

37:54Dr. Mark Hyman:Are they effective? What percent are they effective for? Who are they effective for? And where are we failing with these medications? We're failing on a lot of fronts. I mean, even in traditional psychiatry literature, you know, the word is treatment refractory depression, no response to medicines, is at least a third. And those two-thirds that, quote, got better, they still have symptoms. You know, they've only shown improvement. And I think that the limitations are, it's just symptomatic-based treatment without looking at the cause. But what has happened for too many years is the psychiatric community completely ignored what happens when you stop these medications.

38:37And, you know, I call it withdrawal. They call it discontinuation syndrome. Either way, it's pretty significant for some individuals. And this is where I think functional medicine can play a unique role in the field of psychiatry. Because I'm quite convinced if we do these functional medicine tests before someone stops their medication, we can completely eliminate those withdrawal symptoms. and it was just kind of eye-opening and probably 10, maybe 15 years ago when I had two people stop the same medicine. It was Celexa and one person did it fine and the next one had these intractable, you know, brain zaps and suicidal thoughts.

39:22And I realized what's not the medicine, it's what's going on in that individual. And once we do the functional testing, we replete the D and the B12 or the amino acids, we can safely withdraw someone from these antidepressants.

39:36Dr. Mark Hyman:So basically what you're saying is get all the fundamental imbalances and dysfunctions sorted, test for them, address them, correct them, kind of like the orthomolecular concept of correcting the molecular dysfunctions, and then you'll find an easier way of tapering off the medication. Oh, absolutely. I've just seen it thousands of times. What these antidepressants do, they kind of trick the brain, particularly the SSRIs and SNRIs, the Prozac. And the brain adapts to this medication, which means there's a functional serotonin deficiency. So there's less serotonin being produced. So if you have deficiencies in any of the cofactors in serotonin synthesis, that you pull this drug and your brain just goes crazy and doesn't know what to do.

40:26But if you can replete that process, then it becomes much more manageable, and we can eliminate those side effects.

40:35Dr. Mark Hyman:Do you try to mostly get people off of these drugs? Most of my work now is people who have struggled with inability to come off their antidepressants, they've been feeling okay, or just side effects, whether it's weight gain, sexual side effects. So that's why a big part of what I've been doing is supporting people coming off the medications. And where do you find resistance to the effects of actually working with patients with this model? Where are the ones you find are treatment resistant to using a functional medicine, sort of more holistic psychiatry approach? In terms of the patients? Yeah.

41:16Dr. Mark Hyman:Some people do better, but some people don't necessarily. There are patients who want the quick fix, and that's what they're used to, and they want the medication, and we need to kind of respect that. And then what our role is that these micronutrients will just minimize side effects and support, you know, their recovery. You know, other patients, you know, are interested in digging deeper and looking at the root cause, as you described. Most of the time I'm looking at the literature, these psychiatric drugs do sometimes help people with major depression. But if you look at the literature objectively, at least what I've seen, and there's some big trials that look at this, that for mild amount of depression, it's not much better than placebo.

42:02Dr. Mark Hyman:They might work, but so does placebo, right? So does a sugar pill. And so if they're much better than placebo, then why are we prescribing them given they have all these side effects? Yeah, no, I used to have a picture of M &Ms. And, you know, you know, because some of the research, you know, the best research may be 60 percent or, you know, and other people coming up with 50 percent. And that's what placebo will help. I mean, placebo has a powerful effect on depression. And we've known that for years. That's why there was a lag in drug development because they couldn't beat the placebo. So that's why, you know, we haven't given up our skills and training in therapy.

42:42And part of the reason, you know, the name of the book is kind of helpful because that therapeutic alliance and our ability to instill hope in our patients is just, you know, the first step.

42:54Dr. Mark Hyman:Yeah, I mean, the name of your book is quite good. It's Finally Hopeful, The Personalized Whole Body Plan to Find and Fix the Root Causes of Depression. And honestly, James, medicine is really not focused on root causes. It's focused on describing the disease, the symptoms, and then trying to suppress those symptoms with a medication or modify some downstream pathway rather than dealing with the upstream root cause. And that's really what you and I have been doing for so long is actually how do we actually think about getting into root causes and treating the body of the system and then looking at the things we can actually measure and test.

43:29Dr. Mark Hyman:We did talk about this a little bit on your last podcast with me, but it might be worth sort of touching base again, because I think, you know, you've been to know the leaders in nutritional lithium supplementation, low doses of lithium, not the massive doses you get for people with bipolar disorder or manic depressive disorder. but you're saying it's often missing and it's it's um there's a lot of kind of research globally on how it may be linked to suicide and and genetics how they play a role and and talk to us about the role of nutritional lithium and how how you use it in clinical practice and how you assess it i mean i think lithium uh orotate nutritional lithium is one of the most important tools in my toolbox as a psychiatrist.

44:15And again, 2025, the year of research, just a stunning paper came out of Harvard published in Nature, where they demonstrated that one, lithium was low in the brains of Alzheimer's patients. So it was one of 50 elements tested. And then two, that lithium orotate in these mice models that develop Alzheimer's pathology, lithium orotate was able to prevent and reverse the neuropathology of Alzheimer's. So it was one of the most stunning things and it was not lithium carbonate. So the other forms of lithium did not reverse the plaques and tangles, but only lithium orotate. And I think you can appreciate this.

45:04Dr. Mark Hyman:I saw that paper. Yeah, we've been talking about lithium orotate, but everyone who commented on the study said, brilliant, great, but we need more research because we've never used lithium orotate. And we've been prescribing it for 30 years. So it just kind of helped us as clinicians. But lithium is an essential element for brain health. And I'm quite convinced there are some individuals that just have a little higher need based on family histories, particularly addiction or bipolar. And sometimes two to five milligrams of lithium has been some of the most traumatic changes we've seen in depression and other mental health problems.

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46:26Dr. Mark Hyman:And because they're chews, not pills, they're convenient and delicious. Perfect for your bag, your desk, or wherever the day takes you. If you want a simple way to support resilience, energy, and focus this summer, try HTB Immune Energy Chews. Go to BigBoltHealth.com slash DrHyman, that's D-R-H-Y-M-A-N, and use the code HYMAN15 to save 15 % off your first order. And how do you know if someone needs that? Good question. So symptoms, I look at irritability and impulsivity. So moodiness, irritability, and that could be in an ADHD kid or depressed person. And then family history is important to me as well.

47:08So family history of depression, addiction, bipolar, or suicide.

47:14Dr. Mark Hyman:And do you measure like lithium levels in the hair or how do you sort of assess? Yeah, yeah. Blood levels won't help because the blood levels only pick up pharmaceutical lithium. So I do look at a trace mineral hair test on everyone. And oftentimes we can see now undetectable lithium. But even if there's lithium in the hair, sometimes we'd use it as a nutritional supplement. So I think, you know, one of the things that we get into medicine is binary thinking. It's either this for that, it's either only, you know, holistic or only medicine. And the truth is, we need an approach that integrates all modalities, whether it's functional medicine, psychiatry, and root cause analysis, and addressing the imbalances in the system, combined with talk therapy, combined with other trauma -related therapies, combined with medication.

48:01Dr. Mark Hyman:So it's really a spectrum of things that we have to choose from. It's just that there's a whole toolbox that we never addressed, which is the toolbox that you and I use that gets ignored by traditional medicine. Talk to us about how you think about more of an integrated approach to mental health. Sure. I think many, both the doctors and patients, are struggling with, you know, do I take supplements or do I take medications? And everything that we talk about in the book can be utilized, you know, with medications. And oftentimes, looking at these functional tests, utilizing the supplements while someone's on medications is a path to help someone taper off the medications.

48:43But I think depression is complicated for some individuals and, you know, having given up my prescription pad if needed and certainly the role of psychotherapy, whether it's couples therapy, family therapy, you know, or trauma therapy can be incorporated into treatment models. So we don't have to pick one or the other, but we have to embrace all. that's right i mean i always i always jokingly say you know it's a lot harder to be you know happy

49:15Dr. Mark Hyman:uh or enlightened if you're mercury poisoned or your b12 is low your thyroid's not working you have a lot of gut issues fix those things and then you see what's left and then there may be issues that are more from your childhood or more you know from development issues or life stresses but you know often people mislabel the problem and and they go you have depression It's just a totally a mental issue. It's all in your head. So we have to do things that affect your brain chemistry or your talking, your therapy, which doesn't really address the root causes. So I think root cause medicine is sort of where it's at.

49:53Dr. Mark Hyman:I think it's something that's coming up. And also the whole idea of treating the system, not just individual symptoms, which we do in psychiatry. And I think when you're doing is really a more comprehensive approach and you're doing things that most psychiatrists don't do, which is you're doing blood tests, you're doing stool tests, you're doing urinary tests, for toxin testing, hormonal testing. I mean, these are things that are just so outside the scope of what most psychiatrists actually look at. So I mean, I think it's impressive. We've been doing this for a long time. You see these patterns.

50:26Dr. Mark Hyman:And I think your book, Finding Hope, is really a great summary of a lot of these things you've learned over your lifetime that help provide actual hope for people who are struggling with this. So I think anybody listening, anybody struggling with depression, anybody having a hard time, for sure, you should get Dr. Greenblatt's book, The Personalized Whole Body Plan to Find and Fix the Root Cause of Depression. It's out now. You can get anywhere you get books. You can find out more about Dr. Greenblatt at jamesgreenblattmd.com. He's got many courses for professionals, and he's training a lot of doctors and psychiatrists how to do this thing, thankfully.

51:01Dr. Mark Hyman:But Also, you've launched a new online platform, which is a functional psychiatry clinic that's focused on delivering personalized root costs mental health for people of all ages called Finding the Living. Can you talk more about that? I think that's really kind of an interesting model. And I think for people listening and struggling, it might be something that you might benefit from. You know, we've been training doctors for a long time, and I think we wanted to kind of work as a group to provide a consultation model to offer, you know, functional psychiatry to more individuals. So I think in the next month, we should have clinicians licensed in all 50 states to not take over treatment, but to really do the testing, provide the consultation, and help people get on that path to recovery for those struggling with depression.

51:51Dr. Mark Hyman:Thank you for doing this. It's so important. I think, you know, it's much needed because people are struggling out there. So I think for people listening, just realize that, you know, if you're depressed or you struggle with mental health issues, you have someone you love who is, that there is a roadmap to thinking about this. There is a systematic way of assessing somebody through deep root cause testing, through comprehensive, you know, history taking to find out what's going on. And through that, we often find the clues that help us really solve these patients' problems and relieve a lot of suffering, which is so necessary given the scope and the kind of incredible amount of people who are struggling with these issues.

52:29Dr. Mark Hyman:I think probably, I mean, the data is sort of staggering. You know, like when you look at the globally, it's, I think like over, you know, 300 million people suffer from severe depression. And it's worse in older adults. It's, you know, tremendous amounts of suicide and almost a third leading cause of death in ages 15 to 29. so I think we need to kind of revise our framework, revise our thinking and actually help people with a new model and I think you've laid it out so beautifully and you've been doing this work for so long so thank you for keeping at it, you could be retired and playing golf, you know, so I really appreciate your work.

53:09There's more work to be done.

53:10Dr. Mark Hyman:There is 100%, so thanks so much for being on the podcast and helping us understand the deeper level of how to think about mental health, particularly depression and all the options there are for both assessing and treating these people. Great. Thanks for having me. Nice seeing you, Mark. My pleasure. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts.

53:42Dr. Mark Hyman:And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health, where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional.

54:12Dr. Mark Hyman:This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public.

54:44Dr. Mark Hyman:So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.