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Psychiatry, Education, Insight. Docs Tracey and Paul Discuss it All! Two psychiatrists — Dr. Paul E. Keck Jr., MD and Dr. Tracey Goodman Skale, MD of TMBO (Two Minds, Better than One) — illuminate mental illness, teach signs and symptoms, dispel myths, and advocate timely care and dignity. Nearly 70 years of combined expertise. DISCLAIMER: educational/general discussion only, not personalized medical advice; in crisis call the 988 Suicide & Crisis Lifeline.
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Welcome to the Two Minds Better Than One podcast, Docs Tracey and Paul discuss it all.
Tracey Goodman Skale, MD:Hello, everyone. I'm Doc Tracy and my husband Doc Paul here, and we're here with Docs Tracy and Paul Discuss It All. Today, we are talking about depression. Paul, do you wanna kick it off?
Paul Edgar Keck, Jr, MD:Yeah. So I think we've got a lot of ground to cover because this is a very big public health problem. It's a malady that affects many, many people in our society and worldwide. And maybe the way to start is to define it. What is depression and what is it not?
Paul Edgar Keck, Jr, MD:So the DSM-five TR that we've referred to before, the official compendium of psychiatric illnesses, defines depression as depressed mood lasting at least two weeks, and that's not arbitrary. It comes from good research looking at how long untreated depression lasts, and then accompanied by a lot of so called vegetative symptoms. And the vegetative symptoms are really about or manifestations of the part of the brain called the limbic system, which I know you're gonna talk about shortly, that controls basic biological functions, sleep, appetite, sex drive.
Tracey Goodman Skale, MD:Energy.
Paul Edgar Keck, Jr, MD:Energy, concentration, the things that occur, that part of the brain is actually evolutionarily a primitive part of the brain. All mammals have a limbic system. So it's affected, by our prefrontal cortex, which is the thing that makes us human, where our personality, decision making, things like that arise. So, at any rate, those are the core symptoms, and we shouldn't forget suicidal thinking.
Tracey Goodman Skale, MD:So, what's the difference between depression and sadness?
Paul Edgar Keck, Jr, MD:Many people with depression actually don't feel sad. They just feel nothing.
Tracey Goodman Skale, MD:And that's a surprise to a lot of people because you think, Well, major depression, I must have depression. And we've heard many patients say, No, I don't have depression. I don't feel depressed. But you're right. They have apathy, they feel numb.
Paul Edgar Keck, Jr, MD:It's like emotional anesthesia, which is a terrible feeling.
Tracey Goodman Skale, MD:Right, like that term. Anhedonia is something they have to have. If they don't have depression, they have anhedonia, lack of interest, and usual pleasurable activity. So, that's something I know we look for in our practices. You'll have somebody that we know they're really into their grandchildren, for example.
Tracey Goodman Skale, MD:And you ask about, Oh, before we get started, what's going on with the grandkids? And I don't know. Or, They're really into sports. I don't know a lot about sports, but I would try to for my patience sake. And it would be football season and Super Bowl, and I know this guy was really into football, and I'd say, Oh, you're watching the Super Bowl?
Tracey Goodman Skale, MD:Uh-oh, those are big red flags.
Paul Edgar Keck, Jr, MD:Yeah, inundity, there's a bunch of different definitions of it, but it's really inability to feel pleasure or joy. No joy whatsoever.
Tracey Goodman Skale, MD:No joy. That's correct. And we're always seeking joy. But I always say, too, the opposite of depression is not happiness, it's vitality. Good work.
Tracey Goodman Skale, MD:Yeah. Having that joie de vivre, basically. Things to look for with depression. You said a two week period. It's not that you're just sad over the weekend.
Tracey Goodman Skale, MD:It's an extended period of time where you're either depressed or you have anhedonia. I know you have mentioned at some point, sometimes people have irritability. That gets tricky, and we'll get into bipolar disorder other times.
Paul Edgar Keck, Jr, MD:Irritability is really a nonspecific
Tracey Goodman Skale, MD:You get that with so many
Paul Edgar Keck, Jr, MD:It just reflects people are miserable for whatever reason.
Tracey Goodman Skale, MD:Right. But you're right, it affects sleep, appetite, energy levels. Sometimes people feel hopelessness, helplessness. And you talked about thoughts of death. Sometimes it's not so imminent, I'm planning to harm myself.
Tracey Goodman Skale, MD:It could be something like, Well, I know I have diabetes, but I'm not going to take my metformin or something like that. Or, Oh, they said I had a spot in my lung, but I'm not going to check that out. Or, Maybe people would be better off without me. These are kind of these long term things. You can't hospitalize somebody for that, but it's definitely something to watch out for.
Paul Edgar Keck, Jr, MD:Yeah, those kinds of feelings are usually the tip of the iceberg and evolve into untreated, more active. Or devolve, yeah.
Tracey Goodman Skale, MD:Devolve. One of the two, right? Yeah. Right.
Paul Edgar Keck, Jr, MD:To more active suicidal thoughts.
Tracey Goodman Skale, MD:So, sleep is hugely important with many disease states, for sure with depression, for sure with bipolar disorder. When I was in medical school, sometimes they talked about if the typical depressed person couldn't sleep, but then some people slept too much, or people have poor appetite, or but some people ate too much, it changes that. And they used to call that an atypical depression. I don't think we talk about that so much anymore, but they used to hint that maybe that was something to do with a bipolar depression. I think now, over time, we've seen that's not necessarily the case, and people are so uniquely different in how they present with their depression.
Paul Edgar Keck, Jr, MD:And people can struggle with depressive symptoms that vary completely between episodes. We call them episodes, so hopefully someone comes out of it with treatment. Someone can have too much sleep, don't want to get out of bed. Used I to call it a hyper hibernation state, all they wanna do is sleep and eat and not move, or in one period of depression and then have the complete opposite, anxiety, agitation, inability to sleep in the next episode of depression. So there's nothing pathognomonic or specific about variability between those two patterns.
Paul Edgar Keck, Jr, MD:The important thing, and I think it reflects our general lack of understanding about what's causing pattern A versus B. There's some theory that, increased cortisol, which I know you're gonna talk about, is more associated with anxiety and agitation and inability to sleep, especially early morning awakening, whereas cortisol can burn out after a spike and being excessive in a hypo or less than normal cortisol state can then cause the atypical symptoms.
Tracey Goodman Skale, MD:That's interesting. I hadn't heard that, but it makes sense actually. It all goes to say these are not pull yourself up by the bootstraps. These are biochemical, neurochemical illnesses.
Paul Edgar Keck, Jr, MD:Yeah, and I think that one confusing thing is people look for a reason. We all want an excuse or an understanding.
Tracey Goodman Skale, MD:Why am I depressed?
Paul Edgar Keck, Jr, MD:Right. Sometimes there isn't one. Often there is. It can be from chronic stress day after day after day or overwhelming stress, terrible loss in one's life. That loss can be a person, it can be a job, it can be all kinds
Tracey Goodman Skale, MD:of So there could be a trigger?
Paul Edgar Keck, Jr, MD:Yes, but not necessarily. Cause after effect, that's the phrase I was looking
Tracey Goodman Skale, MD:Love after effect.
Paul Edgar Keck, Jr, MD:Yeah, we're always looking for a cause after we see an effect. And sometimes it's right and sometimes it has nothing to do with things.
Tracey Goodman Skale, MD:Well, think people understand it more when there is an apparent cause. But when there's not, that's when people get really confused and families get annoyed. Why are you depressed? You have nothing to be depressed about. You have everything anybody could ever want.
Tracey Goodman Skale, MD:And we see people with lots of money and lots of things and lots of success be depressed.
Paul Edgar Keck, Jr, MD:Yeah, and you and I talk about this a lot. If people don't have a sense of purpose and meaning in life, that often is the pathway, the first step towards depression.
Tracey Goodman Skale, MD:And we've seen that with people who retire often. You retire without something else to do that you feel that's meaningful to you, sometimes people fall into depression.
Paul Edgar Keck, Jr, MD:Yeah. I worked with a lot of I don't call them older anymore because I'm that age but older men who retired and were lost. They were vital people who produced a lot of good things in life. And suddenly when that was gone, were lost and they got very, very depressed.
Tracey Goodman Skale, MD:There's some kind of stage, remember the psychological stages, in generativity versus despair. It's just partly being productive and doing things versus not. So that's one of the myths. We're talking about myths intermittently in these podcasts, and one of them is that people that are older don't tend to be depressed. Sorry, opposite of that.
Tracey Goodman Skale, MD:The people that are older, it's a normal part of aging to be depressed. Sorry, that was the total opposite. And it's not a normal part of aging to be depressed.
Paul Edgar Keck, Jr, MD:Not at all. One of the more pernicious things about depression, though, in old age is once you are older than 65 and have depression and get it successfully treated, the recommendations are you never go off an otherwise effective and safe antidepressant because the recurrence rate in anybody older than 65 is one hundred percent after two years if you stop an otherwise effective antidepressant treatment.
Tracey Goodman Skale, MD:Well, that's a sobering statistic.
Paul Edgar Keck, Jr, MD:It's not that different than hypertension or diabetes or all the other chronic illnesses that affect people as they get older.
Tracey Goodman Skale, MD:Good point. And it's really important to stay on your medications without... You should just stay on your medications and don't go off without talking to your provider. I used to have in my office, we would talk to patients about, Oh, did you see your primary care doc since the last time I saw you? What went on when you saw Doctor.
Tracey Goodman Skale, MD:Brooks? Did he change your blood pressure medicine? Did he change your diabetes medicine? And I would have people time and time again say, Oh, I'm not on that blood pressure medicine anymore. Really?
Tracey Goodman Skale, MD:Why? Well, because when they took my blood pressure, it was fine. And when they did my finger stick, my blood sugar was fine. And I said, Oh my goodness. Well, it's fine because you were on those medications.
Tracey Goodman Skale, MD:Don't stop taking those. And by the way, then what are you doing with your psych meds? Because particularly when people don't feel depressed, they're like, Why do I need to take my meds? So, you said that about older adults needing to stay on meds. What about a younger person that's on an antidepressant, but now they start feeling better?
Tracey Goodman Skale, MD:What's the thinking about that?
Paul Edgar Keck, Jr, MD:Yeah, this is a pretty well studied area and common conversation in a doctor's office or provider's office. In fact, one thing I want to underscore in this podcast, if nothing else, the goal of treating somebody with depression is to get them well. Not just better, limping along, but better, it's well.
Tracey Goodman Skale, MD:Not just response, you want remission?
Paul Edgar Keck, Jr, MD:Remission, yeah. And with the tools we have, both psychotherapeutically and with medicines and other interventions, that should be an achievable thing, and that should be the goal. So the data from a lot of research studies show that if somebody... So let's say take 100 people who did well on antidepressant A, when should you or when can you safely stop antidepressant A? And the studies show that if you out, you stop an otherwise effective antidepressant treatment, let's just say treatment, whatever that is, by four months the rate of recurrence is one hundred percent.
Paul Edgar Keck, Jr, MD:Further you go between four and twelve months, the less the chance of recurrence. Longest these studies have ever gone is twelve months, so we don't know beyond that. Twelve months, the rate of occurrence is twenty percent. So eighty percent chance you'll be fine, twenty percent chance, ugh. So I always said it's up to you, the person who's fortunately done well for the treatment of depression, what's going on in your life?
Paul Edgar Keck, Jr, MD:At twelve months, if there's a lot of stress, maybe you
Tracey Goodman Skale, MD:just It's not the time to go off.
Paul Edgar Keck, Jr, MD:Wait another six months or whatever, But it's up to that individual. I try to give them the numbers and the probabilities. The other thing, so that's episode one. The other predictor of depression coming back is number of times you've had depression. So if somebody has had three periods of depression or more, God forbid, in their life, the recommendation is stay on an antidepressant or whatever treatment you're getting that works indefinitely.
Tracey Goodman Skale, MD:Right. I actually maybe have been more conservative than you on that. So, I learned one year, stay a year on an antidepressant, and then again, you could go off at that point and saying the same statistics to them, the eighty percent, twenty percent. But then if they had a recurrence, then I say just stay on forever. So I don't wait three or four or something.
Tracey Goodman Skale, MD:Yeah, Episode, and stay on.
Paul Edgar Keck, Jr, MD:I think that's part of the informed consent process. I think there's a myth that doctors are decision makers, except in rare instances, we make recommendations.
Tracey Goodman Skale, MD:Well, I talk about shared decision making all the time. Even some of my patients had psychosis and they had disorganized thinking and all that. And even then, we were trying to do shared decision making no matter what. Or even we had people with forensic statuses who had legal issues that were forcing them into treatment. And even then, we were still trying to do shared decision making.
Tracey Goodman Skale, MD:So, that's what I always preach to the people that work with me, always shared decision making.
Paul Edgar Keck, Jr, MD:I always called it a partnership.
Tracey Goodman Skale, MD:Yeah. I like that.
Paul Edgar Keck, Jr, MD:Why don't you, if you don't mind, given your neuroscience background, talk about the neurobiology of depression?
Tracey Goodman Skale, MD:Thank you. You know I love neuroscience, so I love talking about it. But just to be certain, I also have a little bit of OCD, which will be something we talk about later on, not to clinical proportions. I don't want to miss anything, so I have some note cards. I actually do have some note cards.
Tracey Goodman Skale, MD:Oh, but that reminds me. Somebody said, Can you be a little bit depressed, a little bit this, a little bit? You can. You can be a little bit of all kinds of things. You can be a little on the anxious side, a little on little bit signs of OCD, but it's only when something adversely affects your life and different aspects, your job, your relationships, etc, that that becomes a problem.
Tracey Goodman Skale, MD:So, everybody that's just a little bit anxious out there doesn't mean you have to rush to see a psychiatrist or a therapist. What?
Paul Edgar Keck, Jr, MD:I think it depends on the pain.
Tracey Goodman Skale, MD:Well, if it adversely affects you. So, if it gets to a level that it's doing that. So, I just wanted to throw that in there. But I'm actually going to put my cool glasses on for this just so I don't miss. So, neuroscience is so fascinating.
Tracey Goodman Skale, MD:The brain is the final frontier. We've come so far, but we have so much further to go. But it's exciting. Look at what's changed just in the time we've been practicing. We didn't have very many medicines.
Tracey Goodman Skale, MD:We have so many medicines now and other therapeutic choices, and it's still not enough. But it gives us hope for our patients, right?
Paul Edgar Keck, Jr, MD:Safer, better treatments.
Tracey Goodman Skale, MD:Right, and that's what we're always looking for too. Oh, some of the treatments long ago. Remember in the days of tricyclic antidepressants, so that's all we had. When I was in medical school and residency, we had the amipramine, desipramine. I'm sure most young providers don't know any of those things anymore.
Tracey Goodman Skale, MD:But they were highly anticholinergic. Were Just a lot
Paul Edgar Keck, Jr, MD:a mechanism in the brain.
Tracey Goodman Skale, MD:A lot side effects with it, constipation, dry mouth. But the biggest problem with them is if you took too many, you die. You can have heart block and die from that. So, it was very dangerous. And I remember in the hospital setting people saying, Be careful when you start an antidepressant because people are still depressed, but now they're energized.
Tracey Goodman Skale, MD:They have the energy to harm themselves. Now we have other options. Not recommended that you take high doses of any of these things necessarily, but if you do, it probably wouldn't hurt you the way the original medications would.
Paul Edgar Keck, Jr, MD:Well, brings up that, so panoply of symptoms for depression. One of the things we do as clinicians is make a list, good thorough list of the problems someone's struggling with, the symptoms of depression, when they come for treatment, and then they track them. Good research has shown they don't all get better right away. There's a kind of chronology. And so you brought up sometimes energy improves before mood, and that's kind of a dangerous
Tracey Goodman Skale, MD:That's a dangerous period. Rating scales. There's so much to talk about. Again, we're talking about everything and not necessarily in order. Rating scales are really important.
Tracey Goodman Skale, MD:If you are a clinician out there, if you can do rating scales, it's important. Patients do self rating scales. Some EMRs don't have that capacity, but if you can, it's good because of some objective findings. The patients like that too. They're like, Oh, I had a 20 rating scale this time and now I'm a 10.
Tracey Goodman Skale, MD:They can objectively see that. Let's dive into some neuroscience. You'll hear about HPA. So, it's the hypothalamic pituitary adrenal axis, and that's the body's primary stress response system. People
Paul Edgar Keck, Jr, MD:are Where is the hypothalamus?
Tracey Goodman Skale, MD:Is the hypothalamus? You tell me.
Paul Edgar Keck, Jr, MD:It's the base of the brain. Right. I'm just trying to give people an image.
Tracey Goodman Skale, MD:Oh,
Paul Edgar Keck, Jr, MD:So, hypothalamus, pituitary, adrenal, they're not all connected.
Tracey Goodman Skale, MD:No, they're not all connected. Sorry, I didn't know what you were trying to get at. It's a whole system. Yeah, the axis. So, people who are depressed often have a chronically overactive HPA.
Tracey Goodman Skale, MD:So, that's what we're going to refer to as the hypothalamic pituitary adrenal axis. Overactive HPA axis. So, this leads to a constant excess of stress hormones, particularly think cortisol. Many of us have heard of cortisol and increased cortisol when you're under stress. That can alter brain cells and mood regulating neurotransmitters.
Tracey Goodman Skale, MD:So, does this all work? The hypothalamus releases corticotropin releasing hormones. So, there is an acronym for that too. So, it's CRH hormones in response to stress.
Paul Edgar Keck, Jr, MD:And how does that stress get perceived?
Tracey Goodman Skale, MD:I don't know what you're doing. So, go ahead. Do what you want here.
Paul Edgar Keck, Jr, MD:So, it's not like the hypothalamus has eyes.
Tracey Goodman Skale, MD:Yes.
Paul Edgar Keck, Jr, MD:So so so it's... I'm just trying to order... Orient people.
Tracey Goodman Skale, MD:So Well, then I'm gonna ask you to not ask me that because I don't know what you're doing. I... So I'm I'm on a roll here.
Paul Edgar Keck, Jr, MD:So, we experience stress by things that we perceive. Frontal cortex.
Tracey Goodman Skale, MD:Right.
Paul Edgar Keck, Jr, MD:That sends signals to the hypothalamus. Yes. And then the cascade starts. Sorry to interrupt.
Tracey Goodman Skale, MD:Right. But from now, I'm gonna ask you if you have that image just because you know what you wanna say, it sounds like. It sounds like you have a very clear thing of what you're wanting to say, and I'm going to roll here because I'm excited. So, CRH triggers the pituitary to secrete ACTH, that's adrenocorticotropic hormones, into the bloodstream. So, it's this cascade, as Paul had mentioned.
Tracey Goodman Skale, MD:ACTH signals the adrenal glands to release cortisol, which mobilizes energy in the form of glucose.
Paul Edgar Keck, Jr, MD:And the adrenal glands are above the kidneys. They're not in the brain.
Tracey Goodman Skale, MD:No, no, no. So, that's what's so fascinating. And There's the mind body connection. I'm glad you brought that up there. I'm going give you credit for that one.
Tracey Goodman Skale, MD:There is the mind body connection. We are all connected. We're one human. It's not all just in the brain. It's not all from the neck up.
Tracey Goodman Skale, MD:So, as psychiatrists or anyone that's a psychiatric provider, we're not just working from the neck up. It's a total body phenomenon. So, this gets the body in fight or flight mode, which people have heard of before. Fight or flight can be good if a bear is chasing you. That's important.
Tracey Goodman Skale, MD:It wouldn't be good for you to chronically have a bear chasing you and have that level of fight or flight, right? So, in so called normal function, high levels of cortisol signals the hypothalamus and the pituitary to shut off the stress response. So, if we're not in a depressed or anxious state, then we're shutting off that response over time. But, if the person has depression, the feedback loop starts to break down, creating a cascade of neurobiological consequences. The brain's cortisol receptors, which are glucocorticoids, become desensitized and cortisol production is not turned off resulting in chronic hypersecretion.
Paul Edgar Keck, Jr, MD:And by the way, these are not anabolic steroids.
Tracey Goodman Skale, MD:These are corticosteroids. Corticosteroids.
Paul Edgar Keck, Jr, MD:Totally different And
Tracey Goodman Skale, MD:endogenous there too. So, if this goes on too long, the hippocampus can atrophy and because high levels of cortisol become neurotoxic. So in my office, I had all kinds of inspirational quotes, which are the most important thing, but I also had all these brain charts and brain models because neurobiological illnesses. The hippocampus is involved with mood regulation and memory, so we don't want to be messing with the hippocampus. Increased cortisol also decreases what we call BDNF, which is brain derived neurotrophic factor, which is essential for the growth of brain cells.
Tracey Goodman Skale, MD:Unchecked, cortisol also stimulates pro inflammatory cytokines which alter neurotransmitter production. So, when we talk about neurotransmitters, think serotonin, norepinephrine, dopamine, that kind of thing. And that in turn deepens depressive symptoms. Other neurotransmitters that are getting some attention now are glutamate and GABA. So glutamate is excitatory, GABA is inhibitory.
Tracey Goodman Skale, MD:Not excitatory like that's a good thing. It's within the neurotransmitter system. So, these neurotransmitters are increasingly recognized as central to mood regulation. They're involved in newer treatments like ketamine, which blocks glutamate.
Paul Edgar Keck, Jr, MD:Blocks a glutamate receptor.
Tracey Goodman Skale, MD:So, more neuroscience. Hyperactivity in the amygdala leads to increased reactivity to negative stimuli, and the nucleus accumbens, just some more fancy terms to throw out here, is associated with reward. So, if you have a dampening in your nucleus accumbens region, you can't feel rewarded. So, you're in a chronically depressed state, you can't feel joy. So, it all goes back to that loop we discussed.
Paul Edgar Keck, Jr, MD:The amygdala is like the panic button of the brain. And so, when it becomes over reactive, then you feel chronically anxious. Vicious cycle.
Tracey Goodman Skale, MD:Right. Chronic stress causes reduction in neuroplasticity. So, you often will hear people talk about neuroplasticity of the brain and the importance of doing crossword puzzles and all these things to keep your brain stimulated and nerve cells growing, chronic stress is damaging to that process. So, get ineffective communication between nerve cells. Bottom line, we need to decrease our stress, we need to decrease our overall inflammation, but again, it's this whole mind body thing.
Tracey Goodman Skale, MD:And then, by the way, there's all kinds of research going on between the gut brain connection as well, and that involves inflammation. So, thanks for indulging me and letting me talk a little bit about receptors and HPA and all that kind of thing.
Paul Edgar Keck, Jr, MD:Well, there are a lot of real world experiences you and I have had working with people with the system going awry. And one of the key symptoms of depression is early morning awakening. Mhmm. And that happens... That's a clear marker that somebody's cortisol is elevated.
Paul Edgar Keck, Jr, MD:And early morning awakening means, like, three, four in the morning compared with when they would normally wake up. But I can remember, when the market crashed in 2008 around the whole real estate disaster. And I saw for the first time about a dozen men, there just happened to be men, who were in the finance industry. No prior psychiatric struggles at all, but their portfolios had crashed. And it wasn't just their own losses, they were horrified because they were managing money for a lot of other people.
Tracey Goodman Skale, MD:So responsible for a lot of people.
Paul Edgar Keck, Jr, MD:And felt very guilty about that. And then they started watching the markets 20 fourseven. Just incredibly unhealthy. And there's nothing you can do about it until you're you're open for business. So actually one of the very first things I suggested to all of these men was quit watching the markets until you can do something about it.
Paul Edgar Keck, Jr, MD:So part of stress is a perceived inability to control a potential adverse outcome. And this gets us back to the Stoics, but one important sign of good mental health to ward off risk of depression is, What can I control?
Tracey Goodman Skale, MD:Also anxiety, though, too. So that's an anxiety. Depression often is seen as a lot of times people are ruminating about things in the past that they cannot fix, and then they're depressed about it. Anxiety, a lot of worrying, thinking about the future and trying to anticipate the future, and then they're anxious about that. So, it's for both anxiety and depression.
Paul Edgar Keck, Jr, MD:Yeah. And anxiety and depression go like this for most people.
Tracey Goodman Skale, MD:Tell me some more stoic thing. You liked reading about the stoics. What else?
Paul Edgar Keck, Jr, MD:That's the main one.
Tracey Goodman Skale, MD:With mental health.
Paul Edgar Keck, Jr, MD:Focusing on what you can control
Tracey Goodman Skale, MD:And present.
Paul Edgar Keck, Jr, MD:Your own feelings and being present. There's a lot of stoicism and dialectical behavioral therapy. And
Tracey Goodman Skale, MD:that will be fun to talk about that when we get into all the different kinds of modalities of therapy. So I just mentioned rumination. So that's part of depression too for some people, excessive guilt, ruminating. They can't concentrate, partly why they can't sleep. They're going over and over things in their heads sometimes.
Tracey Goodman Skale, MD:We talked about thoughts of death and sometimes plans to harm themselves. It's really important for our clinician listeners out there that you're not afraid to ask about suicide. Some people have the false belief that if you talk about suicide, that's convincing the person to do it or giving them the idea to do it. You're not giving them the idea to do it. They've probably thought about this before.
Tracey Goodman Skale, MD:And you always talk about, Paul, matter of fact, and I like that. There's not emotion associated with it. It's just a factual conversation. So, it strikes me that you're talking a lot about being depressed. Have you had thoughts of harming yourself?
Tracey Goodman Skale, MD:Very matter of fact about it. It's a really important part of our mental status exam. We always ask that with our patients, correct?
Paul Edgar Keck, Jr, MD:Yes.
Tracey Goodman Skale, MD:And the same thing for family and friends. We don't want to skirt around that. If you think that something is going on, it's okay to have that conversation that you are worried about them. Sometimes you'll hear people say that have thought of suicide or actually attempted suicide that I know I've had this in my practice over three decades for sure, and I'm sure you have that they were planning to do something, but then they get a phone call they got something nowadays a text that somebody was thinking about them or somebody out there cared about them and that made them stop.
Paul Edgar Keck, Jr, MD:And sometimes it's just the encouragement of a well meaning family member, friend, healthcare provider to say, Hey, we'll get this.
Tracey Goodman Skale, MD:And we care.
Paul Edgar Keck, Jr, MD:We care. Hang in, solvable problem.
Tracey Goodman Skale, MD:I
Paul Edgar Keck, Jr, MD:have treated three people in my forty years who died by suicide. In none of those instances was that something I would have predicted. So part of, I think, the difficulty is people are also very secretive, ambivalent. One hour they may be okay, next hour hopeless. Obviously, people who die by suicide, you can't talk to them.
Tracey Goodman Skale, MD:May I ask the people that died by suicide, were they all depressed?
Paul Edgar Keck, Jr, MD:Yes.
Tracey Goodman Skale, MD:So, I have had a few people also who have died by suicide. That's expected in this work, especially if you're working with people who are very ill. Interestingly, my people all had psychosis. And it was a refractory psychosis situation. And actually, for me, it was not surprising for the particular people involved.
Paul Edgar Keck, Jr, MD:And I think that illustrates a couple points. One is it's not only depression that is associated with suicide. There can be a lot of other psychiatric struggles. These are illnesses that are serious and that they sadly do have a mortality rate, not just morbidity or sickness. No, I forgot what I was gonna say.
Tracey Goodman Skale, MD:Well, while you're thinking, can I ask you something then before I forget? We talked about depression in older population. What about depression in young people? Because that is a myth. That's the myth that young people don't get as depressed as older people, and we're seeing increased depression.
Paul Edgar Keck, Jr, MD:Second most common cause of death in people sixteen to twenty... No, 16 to
Tracey Goodman Skale, MD:Accidents 30 and homicide or
Paul Edgar Keck, Jr, MD:something, right? Suicide is right there. And there are good data that... I mean, none of these statistics are static because things change over time, hopefully for the better. But numbers for adolescents and young adults struggling with depression and anxiety and suicide risk shot through the roof with COVID.
Tracey Goodman Skale, MD:Part of it is the isolation.
Paul Edgar Keck, Jr, MD:I think that's a big part of it. And I think we're still living with the aftermath of that. But social connection is another key thing. Sense of purpose and meaning. Friends.
Paul Edgar Keck, Jr, MD:Authentic friends.
Tracey Goodman Skale, MD:Sense of belonging. That's why we often encourage people to do activities. I always tell my patients, We need to get you outside of your head. Two people are ruminating, whatever the disease state. They're just kind of stuck inside themselves.
Tracey Goodman Skale, MD:And whatever their religious affiliation or not, get involved with a church or something maybe or other kind of volunteer activities, things to get them around other people. So, that's again the older population, sometimes especially after retirement. And if they have a loved one, their spouse passed, they're by themselves. They start turning inward more and more, don't they?
Paul Edgar Keck, Jr, MD:Yeah. It's called involution. Involution. Yeah. The better we all have a sound, you don't need a thousand friends.
Paul Edgar Keck, Jr, MD:A buddy of mine in college once said, somebody only really needs two or three good And he was right. I was like, woah, where did that come from? He was 20 years old. But I think that's true. Because without those connections, then, well, you have no reason to keep going.
Tracey Goodman Skale, MD:The other thing we had talked about a little bit earlier is when you're in a depression, sometimes you feel like you just want to stay in bed and you don't want to do anything. Those self help type of books, you know, Make Your Bed, Wash Your Face, all that, there's something to that. There really is something to that. I say to my patients all the time. I know you might want to feel like you want to stay in bed and pull the covers over your head, but you will not get better doing that.
Tracey Goodman Skale, MD:No one gets better doing that. And so, you really do have to make some efforts to do a few things. And I know there's a couple of you talk about.
Paul Edgar Keck, Jr, MD:Yeah, is key. It can feel cruel as a provider telling people, You've got to get out of bed, even though that's the last thing on earth.
Tracey Goodman Skale, MD:You're overwhelmed.
Paul Edgar Keck, Jr, MD:You don't want to be sadistic about it, but it's key. I was working with a 72 year old man, former college professor, who after retirement got severely depressed, came to see me with his wife. I tried to distill down everything I learned in forty years as a psychiatrist. One of the key things was the rule of three. Do three things a day.
Paul Edgar Keck, Jr, MD:Even though you don't want to, don't feel like you need, you know, all that, it'll take an hour, at least an hour.
Tracey Goodman Skale, MD:All three take an hour or three together? Each. That's a lot.
Paul Edgar Keck, Jr, MD:It takes an hour. Could be doing the laundry, cleaning up the kitchen, could be going out to have lunch with a friend. That takes an hour. Even a doctor's appointment takes an hour to get there and back. And so when I was...
Paul Edgar Keck, Jr, MD:This person fortunately did very well and he said, you know the most important thing you told me? You know, what? Three things a day. He said, That made all the difference. So, again, it's not what you do, it's being active in getting going.
Paul Edgar Keck, Jr, MD:Although I'm still... A sense of accomplishment. Right?
Tracey Goodman Skale, MD:Yeah. Yeah. Accomplished something. Yeah. Another thing about depression in getting going is we talk about gratitude with our patients, too.
Tracey Goodman Skale, MD:Sometimes they don't see any gratitude because things seem really horrible. But if they can at all, try to write down something, one thing even. Typically, everybody says three things. But if you can find one thing to be grateful for, it could be even that you just woke up that morning or the sun is shining or something. That goes a long way.
Tracey Goodman Skale, MD:That will go into cognitive behavioral reshaping. So, CBT, Cognitive Behavioral Therapy, has been proven to be very effective for people with depression and anxiety. We're talking depression today. So, there's the Feeling Good Handbook. We've worked with our patients with that.
Tracey Goodman Skale, MD:Sometimes a combination of therapy and medication can be really helpful for people. Depression is not just mood. You were talking about that earlier. It's also how we perceive the world. So, some people's perception is very distorted when they're depressed.
Paul Edgar Keck, Jr, MD:Through gray colored glasses. Right.
Tracey Goodman Skale, MD:That's a good way to look at it. So, that's why sometimes they think the world would be better off without them because they're so distorted in their thinking. And if you present in a depressed way, the world also perceives you differently, too. A lower energy, people kind of don't know how to react to you, and then sometimes people pull away.
Paul Edgar Keck, Jr, MD:We were talking about the combination of therapy and other treatments. So, again, old enough to have been around before we had good evidence based research about psychotherapies. Evidence based means good controlled studies, so there's a comparison group and the active treatment group, scientifically rigorous. And the good news is that there are at least three or four evidence based therapies for a variety of psychiatric problems, and you mentioned CBT for depression. The tricky thing I've always found is encouraging somebody to go into therapy when they're severely depressed, they can barely even think, is probably premature.
Paul Edgar Keck, Jr, MD:Supportive therapy. Supportive therapy. So there's
Tracey Goodman Skale, MD:all different kinds of therapy. So in my practice, I did a lot of supportive psychotherapy. So there's different kinds, but supportive psychotherapy goes a long way. So in essence, we are supporting them to get them to a place where they can concentrate on doing the work of therapy because therapy is hard work.
Paul Edgar Keck, Jr, MD:Yes, it is. And so, I guess my only point was that sometimes plugging in the evidence based therapies is staged.
Tracey Goodman Skale, MD:It's not
Paul Edgar Keck, Jr, MD:right away. Depends on the person, depends on the severity, depends on, quite frankly, their response to other treatments. I mean, I've had people do so well on an antidepressant, it's like, why are we wasting time with therapy? They're 100% better. Not that common.
Tracey Goodman Skale, MD:That's not that common.
Paul Edgar Keck, Jr, MD:But I've seen it happen.
Tracey Goodman Skale, MD:Yeah, because therapy can be used. A lot of people need therapy or could benefit from therapy, let's put it that way. Most of us could benefit from therapy whether we're depressed or not. There's always something to work on. So, there's medications.
Tracey Goodman Skale, MD:There are so many different medications out there now that continue to work better with fewer side effects and work quicker. There's augmenting antidepressants with other things to see if they would work even quicker. There's still ECT, electroconvulsive therapy, people think one flew over the cuckoo's nest, it's not like that. That's still a viable option. And we will get into different treatment modalities more specifically.
Tracey Goodman Skale, MD:What are some other ways of treating depression?
Paul Edgar Keck, Jr, MD:Transcranial magnetic stimulation, TMS.
Tracey Goodman Skale, MD:That's really popular now. Vagal nerve stimulation, do people still do that? That was a thing for a while. People were doing that.
Paul Edgar Keck, Jr, MD:It's pretty uncommon.
Tracey Goodman Skale, MD:Uncommon now? Yeah. Ketamine, esketamine, what about that? We talked about that in my neuroscience piece.
Paul Edgar Keck, Jr, MD:Yeah, there's a big difference actually. Esketamine, E S, is cousin of ketamine. Ketamine is actually not FDA approved for the treatment of depression. S ketamine is because of good FDA sanctioned research studies. Now is there a big difference?
Paul Edgar Keck, Jr, MD:I don't know. They've never been compared, but each affects the glutamate system, and there's something about that system. This is new. I mean, a new This
Tracey Goodman Skale, MD:is cutting edge stuff too.
Paul Edgar Keck, Jr, MD:Minds.
Tracey Goodman Skale, MD:An MDA.
Paul Edgar Keck, Jr, MD:Yeah. Nobody was looking at the glutamate system eight years ago. So the point of that is that, these new treatments and there's a there's a pill form, of a combination of drugs that affects that system too, the response seems to be better and faster. And when I say better, remission rates, which we talked about earlier. The goal is to get people well.
Paul Edgar Keck, Jr, MD:So that's exciting. And there are a bunch of new things on the horizon.
Tracey Goodman Skale, MD:Psychedelics, potential So that's also exciting. Were studies that I remember years ago reading about this, that they took a group of middle aged women that had depression, and they had half of them be on an SSRI, a selective serotonin reuptake inhibitor, it's kind of antidepressant. Think Prozac, Paxil, Lexapro, that kind of thing. And they put the other half on an exercise regimen, and they did equally well. When they stop the antidepressant, they get depressed again.
Tracey Goodman Skale, MD:When they stop the exercise regimen, they get depressed again. So, exercise in a holistic approach is really important, too. Fresh air, good nutrition, exercise, all of that is really important. Again, mind body. So, again, we are psychopharmacologists, but we don't just push medication.
Tracey Goodman Skale, MD:Sometimes medication can be helpful. Not everybody wants medication or needs medication.
Paul Edgar Keck, Jr, MD:And I've worked with people where I've said, I don't think medication is actually indicated for you. You really need good therapy. Because it was so obvious that there were struggles.
Tracey Goodman Skale, MD:Right. And you can have a trigger or something can be a real life depressing event. You could be loss of a loved one, a chronic you have cancer now and you're really upset about that. And those are things to be upset about when people can be depressed. There used to be, in the old DSMs, they used to talk about adjustment disorders with depressed mood.
Tracey Goodman Skale, MD:I don't even know if they don't even do that anymore, do they? I don't know.
Paul Edgar Keck, Jr, MD:It's in there.
Tracey Goodman Skale, MD:We just don't talk about that so much. There's a clear precipitant and then you have a clear reaction to it. If it's sustained, then that becomes a problem. So, own father I was in medical school then, so he developed renal cell carcinoma. And he really didn't believe in going to doctors, and here I was graduating from medical school.
Tracey Goodman Skale, MD:I'm like, You really need to go to a doctor. He hadn't been feeling well for a long time. So, he finally begrudgingly went to a doctor and they told him that day, You have metastatic renal cell carcinoma, which was kind of the self fulfilling prophecy. He knew that in his head if he went to a doctor they would say he's going to die, which is what happened. And it's because he waited too long.
Tracey Goodman Skale, MD:He had frank blood in his urine for a year and didn't do anything about it. He was so horribly depressed. Here I in Cincinnati, they were in Massachusetts, and I would call home and if he answered the phone, he would just start crying, sobbing. I had never heard my father cry ever. And this was so different.
Tracey Goodman Skale, MD:And he would say, Why is this happening to me? I can't believe this is happening to me. And he just couldn't function. And I remember talking to his oncologist and primary care doc at the time and saying, I think he needs to be on an antidepressant. Here I was a medical student.
Tracey Goodman Skale, MD:They were like, But he has cancer. He's dying. He has a reason to be depressed. I said, But this is beyond this is yes, but he can't function. He can't enjoy any quality time with his family.
Tracey Goodman Skale, MD:He can't get his affairs in order. He can't do anything. He can't concentrate. They agreed to put him on a low dose antidepressant, and he immediately perked up. So, he was able to concentrate.
Tracey Goodman Skale, MD:He was able to enjoy time with friends and family. I remember being home and he was watching a sitcom and laughing. So, it greatly improved his quality of life even though he had dire consequences of his cancer looming ahead of him. So, I'm a believer in doing what you need to do to help yourself feel better and have the best quality of life. So,
Paul Edgar Keck, Jr, MD:you just talked about your dad and how cancer and medical illness triggered depression and the need to pay attention to both of those things. What about depression as comorbid with other psychiatric and medical?
Tracey Goodman Skale, MD:So many other psychiatric illnesses go with depression or medical illnesses go with depression. One makes the other one worse, so they each exacerbate each other. So, if you have depression, let's talk about depression in diabetes, just like we talked about with the cortisol, you're depressed, Your blood glucose is harder to control. Sometimes your blood glucose is hard to control. You're depressed.
Tracey Goodman Skale, MD:It goes like that. Migraine headaches. We hear headaches a lot with depression and anxiety and bipolar disorder, right? What else did you have to say about that piece?
Paul Edgar Keck, Jr, MD:Well, are somewhat surprising findings from research studies, mostly from Scandinavia but from around the world, show that, people with depression have, again, untreated depression, have a much higher rate of death from cancer
Tracey Goodman Skale, MD:Heart disease.
Paul Edgar Keck, Jr, MD:Heart disease and diabetes compared to the general population. So there's this double edged or negative synergy between depression and these medical illnesses. And then there's, of course, depression occurs so frequently with other psychiatric illnesses, post traumatic stress disorder. In fact, one of the risk factors for depression is what's called early childhood, ECE, adverse childhood experiences. And the younger somebody has a bad traumatic experience, the greater their likelihood of having depression in adolescence and through the rest of their lives.
Paul Edgar Keck, Jr, MD:So we always look for depression when somebody has OCD, PTSD, panic disorder. Substance Substance misuse. Yeah. And conversely, if they have any of those other problems, we look for depression. So you've got to look at the whole playing field.
Tracey Goodman Skale, MD:Right. And we co treat. So if someone... You were mentioning substance misuse. If someone is using substances, sometimes it's a self medicating thing.
Tracey Goodman Skale, MD:They're depressed and they're trying to feel less depressed, or they're anxious and they're trying to feel less anxious, or they're down and they're trying to be up. And then it has a life of its own, but we have to treat comorbidly. I've had someone come in completely intoxicated in my office. We can't do much psychiatrically when that's going on. Or someone literally with a needle in their arm in the parking lot.
Tracey Goodman Skale, MD:We couldn't do much that day other than get them safe. But otherwise, we're treating both. I remember working at the VA and we'd have so many people come in with suicidal ideation, but they were heavily intoxicated. And when the next morning came and they kind of slept it off, they no longer felt suicidal. So, substances can greatly affect your mood.
Paul Edgar Keck, Jr, MD:Oh, yeah.
Tracey Goodman Skale, MD:Did you have any other things you wanted to bring up that we haven't discussed yet, Paul?
Paul Edgar Keck, Jr, MD:Not offhand.
Tracey Goodman Skale, MD:Well, one of the things I wanted to go back to is that we really want remission. And we'll say that with every disease state. We can't always get that, just like you can't always get 100% remission from your cancer. Sometimes you die despite having great doctors and medicines and all these things and prayer and all these things, sometimes it doesn't work out. That can happen in psychiatry as well, but we are always striving for remission of all their symptoms.
Tracey Goodman Skale, MD:You have psychosis, you have mania, you have depression. We don't want these smoldering symptoms. I always say it's embers in a fire. At some point, they'll ignite again. Just like you were saying, if you stop the medications, the chances of recurrence come back.
Paul Edgar Keck, Jr, MD:Well, you and I talked about the role of genetic testing too, pharmacogenetic testing. And one, we're getting better and better at this as a field, but what I worked with in partnership with patients was I can't necessarily say that you're going to be doing great on drug A versus drug D, or that psychotherapy A is going to be better than psychotherapy type B. But what I would say is this is educated trial and error, educated but trial and error. So the best we can do is every treatment has a probability of helping you, but I can't give you 100% guarantee that that treatment will. But you got to stick with me, with me.
Paul Edgar Keck, Jr, MD:We're never going to quit, And the goal is to get you well.
Tracey Goodman Skale, MD:We have to give reasonable expectations because you don't say, Yeah, we're going to prescribe you this and it's going to work for you. I mean, we don't know. We hope so. The reason I like the pharmacogenetic testing is it kind of comes green light, yellow light, red light. We say it doesn't give you the needle in the haystack, but it removes some of the hay.
Tracey Goodman Skale, MD:So, there's some people that are rapid metabolizers. They might need more of something or they might have more side effects with something, and it tells you maybe what things you might want to head toward first and what things you might want to avoid. It doesn't mean you can't be on the bread side. It just means you might need way higher doses of it or much lower doses of it. And then there's some people that have, what is that?
Tracey Goodman Skale, MD:If you have two short alleles in the what, serotonin transporter or something, then we could give you all the Prozac, Paxil, Lexaprobes in the world that never respond to it, and that's typically what people give first, so that's why I like to do the genetic screening.
Paul Edgar Keck, Jr, MD:Yeah, and there are some tests in the pipeline that may actually, I think it's a little premature, but may actually allow a prescriber to say, Oh, it's not just we can't we're able to do more than just look at how you metabolize a drug. We're actually able to look at what that drug is likely to do in your brain beneficially. We'll see, but I think that's likely to come on soon.
Tracey Goodman Skale, MD:But we're really hopeful for our patients that have depression because there's so many options available to them. Like we will always say in every single episode, we're the keepers of hope. We have to keep hope for people, everybody. If your friend, your family member, your client, whatever, you have to be the person that's keeping hope alive because sometimes in their depressed state or whatever state they're in, sometimes they don't see that hope. So, that's a big part of our role.
Paul Edgar Keck, Jr, MD:Never quit.
Tracey Goodman Skale, MD:We never quit. Thank you for spending time with us today. Anything that we forgot to talk about with this depressive episode, we'll bring up in some other episode. But I'm really excited to talk to you about bipolar disorder, Paul, for a lot of reasons, but sometimes major depression recurrent looks like bipolar depression or bipolar II depression. And we're going to get into the nitty gritty about how you make those distinctions, right?
Tracey Goodman Skale, MD:Yep. Thank you so much for your kind attention today. Until next time.