Will lifestyle interventions be accepted as alternative treatments for depression? | Charles Raison
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There are various ancient practices, including meditation, hot yoga, and sauna, that may aid in the treatment of depression. Whether the medical community will embrace these lifestyle interventions remains to be seen. Antidepressants have their advantages and disadvantages, and while they are helpful for a subset of depressed people, a quarter of patients may get worse. Furthermore, certain antidepressants can be habit-forming with long term use. It would be optimal to find a strategy that recruited an individual's brain-body system to impart an antidepressant response. Alternative practices have the promise to create a transformational path that may be protective against depression. In this clip, Dr. Charles Raison discusses his belief that ancient practices are more likely than modern pharmacology to encourage resilience and stave off depression.
- Rhonda: If a person was depressed or anxious, if it hasn’t sort of life event that may be induced that, a divorce or something like that, they go and see a psychiatrist and they get prescribed...
- Charles: A medicine.
- Rhonda: A medicine, typically you know.
- Charles: SSRI.
- Rhonda: SSRI, or something like that. Which aren’t necessarily always effective and could have side effects. There are many of these different lifestyle interventions: the weight loss, the exercise, the whole body hyperthermia via your favorite method, sauna, hot yoga or hot bath. There’s meditation, there’s these, you know, psychedelics which of course, that would be something that you can’t really, it’s not legal yet. But for the ones that are, do you think there’s any hope that the medical community will embrace them, that we’ll start to have a treatment centers that people are now can, they can go and meditate, or do hot yoga or sauna, or they can at least be told by their physician, “Try this?”
- Charles: Oh, yes. Oh, yes, yes. Yes, the science is going to go this way. So it’s very interesting. I mean, I specialize in depression, that’s kind of what I do. And it’s a very, and actually my colleague, Christine Whelan and I, are writing a book about these ancient practices we’re talking about, and looking at it in relationship to the pluses and minuses of antidepressants, right? So there’s an interesting truth, or there’s an interesting thing about antidepressants that’s not widely known, which is... And it’s a lot like a lot of things. So, you know, if you look at, there’s these studies showing that if you start out depressed here, and you do eight weeks with an antidepressant or a sugar pill, the antidepressant gets you down, less depressed. Here’s the antidepressant. Sugar pill, you know, will also get you un-depressed but lesser, right? So you say, “Antidepressants seemed to work pretty well for everybody. You know, they seemed to work better than a sugar pill for people,” but that’s not the truth.
- Rhonda: Yeah.
- Charles: John Krystal at Yale did this great study where they were able... I won’t bore you with the details, but what really happens is about 70% of people will do much better short-term with an antidepressant than they will with a placebo. I mean, they really feel better. So there’s a group of people that really do well with antidepressants. And by ‘well’ here, what I mean is that they were really coming apart with depression and now, you know, couple or three weeks later, they feel like they’ve got their life back. They feel better. They feel fantastic. Twenty five percent of people that are depressed will do much worse with an antidepressant than they would with a sugar pill. And that’s what’s not widely known. We’ve seen a very similar pattern in some of our immune interventions studies. It seems like all interventions, or many interventions, may share this. That if they help some people, they may actually hurt others. So the first thing I say to people is, you know, if you’re depressed and anxious, and if it is impairing your life, I mean, where you’re really having trouble, you know, where you just, you really have it, there is some very good chance that if you take a regular antidepressant, you will feel considerably better, and there’s some chance that you’ll feel like way better, right? That could be very useful, and so it’s just bracket that. I mean, that these agents are very powerful for a not insignificant subset of the population that’s depressed. It’s also possible if you take one of those agents, that in fact, it’s not going to help you. That happens a lot. Now, what you don’t know in fact, is that by it not helping you, you know... So if you look at these studies where what happens is if you don’t respond to an antidepressant, most the time if down is good, you just stay the same. But if I’d given a sugar pill, you would have done much better, right? So you come to me and you say, “I’m just not responsive to antidepressants.” What’s actually happening is that those antidepressants are a absolutely non-optimal intervention for you, right? So there’s a whole bunch of people that antidepressants are not optional for, or are not optimal for. So that’s the first thing. So if you’re one of those people, then what do you do? And that’s where these other things become very, very interesting. But the problem with antidepressants, as I sometimes say, and I, you know, I’m a psycho-pharmacologist. I have seen antidepressants save many lives, and I’ve seen many people benefit from them. But they are a bit of an unearned grace. They take you from a state, when they work, they take you from a state where you just feel horrible about yourself, feel horrible at the world, you’re anxious, you’re miserable, you’re not eating, you’re not sleeping, or eating too much and, you know, you’re just, you’re down yourself. Everything is dark. You can barely get out of bed. You know, you’re scared of your shadow. You can’t make decisions. They can take from that and in a month, you can become like super yourself, when they work. Now you’re confident, you feel better, all that stuff that was bothering, you’re like, “Yeah, what’s the big deal? You know, sue me.” All of a sudden the world responds better. They go, “Oh, I’m so happy to see you.” This is “Listening to Prozac,” that famous book from the 90s, that’s a real phenomenon. But the problem is, and it goes back to what I said about the spring versus the thing where you become dependent on. You’re only that person when you’re taking the antidepressant. You take away the antidepressant, and it fades. So that’s problem number one. What you would really like to do is find a treatment that whatever it does, it induces something that’s less dependent on something external for your sense of wellbeing. The other thing about antidepressants is there’s some data, there are some data that the longer you take them, you may become more and more reliant. You may need them to feel good. There’s some evidence that they may induce a vulnerability, so you have to make a decision in your life, you know, are you going to to be Rhonda alone, or are you going to be Rhonda plus Prozac? And that’s a weird thing.
- Rhonda: Yeah. I think I’ve even seen some evidence where there’s changes in, there’s down regulation of serotonin receptors, for example, and you’re constantly, you have serotonin synapses that’s not, you know, being the reuptake like it should. It’s staying around, and so the receptors are like, “Oh, there’s more serotonin and so we should down regulate.” So again, if you were to take that away, all of a sudden you have down regulation receptors and it, your baseline is now even, you know.
- Charles: So relapse rate, so you can take people, and there’s a lot of studies now. You can take people that have been in full remission, taking an antidepressant for two years, you take it away and 60% to 80% of them will have relapsed within a month. I mean, especially if stop it quickly, right?
- Rhonda: Yeah.
- Charles: Whereas initially, if you take away a placebo, a lot of people do pretty well. So placebo responses are more stable and more long lasting than antidepressant responses. And that is a shocker real, I mean, for those of us in the field. So it really speaks to the fact that the strategy of dealing with the adversities of life, and dealing with depression, which is really sort of an involved response to adversity, I think it’s mostly involved response to microbial adversity, like we were talking about. Just now, that’s what it is, all around the world. You know, if you’re sick, if you’re stressed, if things are going badly and you’re vulnerable to it, that’s what sets you off into depression. Well, you know, it’s much better to take an antidepressant than to kill yourself, or to have your life come apart, or to just fall apart.
- Rhonda: Of course.
- Charles: But it would be even better if you could find something that would allow that antidepressant response to become endogenous to your own brain-body system. That’s where these alternative practices, and I think some of these ancient practices, have promise. I don’t think any of them are antidepressants the way an antidepressant is an antidepressant. I think all these things, what they do is that they set you on a path, or they open a door, for you to begin to transform yourself in ways that are going to protect you from depression. Because one of the things that when you live with depression for a long time, and you watch it, what you see is that the things that tend to make people depressed are those things in their life that are the sort of challenges that emerge out of who they are in terms of their behavior, their thoughts, their feelings, right? So they have a lot of examples, but like a lot of times, people become depressed when they, the person who always chooses the wrong partner. No matter what they do, they always end up with somebody that’s abusive to them, or somebody that, yeah. So what they need to do is transcend that pattern, and if they can transcend that pattern, then a huge driver of their depression goes away. But, you know, when they get depressed it’s because they’re approaching it again, or they give up, or they lie to themselves about it, or they, whatever. Life is like, I believe this deeply actually, that life is like a series of challenges to perfect sort of the functioning of who I am, who you are, as a being, the sort of behavioral and biological organization of yourself as an entity. This is mystical mumbo-jumbo, but I do think that for reasons I don’t fully understand, that this is the challenge of human beings. Is to sort of perfect it. If you do that, that is the ultimate antidepressant strategy. Dalai Lama doesn’t get depressed, as far as I can tell, you know. Because what he’s done, it seems to me, and I know him somewhat, is that he’s transformed the way his brain-body complex works. So he’s in states of mind that are just, they’re just inimical to depression, right? So I think that that in fact, is the ultimate antidepressant strategy. But the problem is that it’s a lifetime’s worth of work, and it’s extremely difficult. But I think that these alternative things are more likely to drive you that direction than our modern pharmacology.
- Rhonda: You make yourself more resilient, right?
- Charles: I think when they work, you make yourself more resilient, and you begin to develop perspectives that line up very strongly with many ancient wisdom traditions about the truths of what it means to be alive in this particular universe with its challenges, which are, there’s a myriad challenges. So I think that that is the ultimate way forward. How that works is interesting, because there’s not, it’s very hard to monetize that. And that’s an interesting challenge, right? Because these other ways are far more easy to make you know billions of dollars off of. Now, how you combine standard pharmacology with this pursuit for the sort of, what I call personal transformation view of antidepressant, you know, thing, that’s another really challenging thing. Sometimes people take antidepressants as an excuse not to face what’s going on in their lives. Like I’ve known many people, and patients that they knew, take an example, they’re in a marriage and they know that it’s just they need to get out, right? But there’s a famous saying that many marriages are saved by the, usually the women, because the guys are dolts, you know. Like many American marriages have been saved by the woman just being put on Prozac, because when it works, she goes, “Yeah, you know I can play bridge. I can play golf. He’s not so bad.” You know, you basically just medicate yourself away from the truth of what you know at a deeper level to be true for you. In that way, you know, the antidepressant is actually working against what I would see is this more optimal way of sort of transforming into to coming into full ownership of who you are. But on the other hand, you know, you can imagine somebody that gets up to a wall, and they know they need to do this, whatever it is, but it’s overwhelming. They can’t do it. You know, you put them on antidepressants for a while and it gives them the sort of chops to hop the wall. Then maybe the antidepressant has become sort of a tool for transformation. I’ve never seen anybody talk much about this, and I’ve only been thinking about it for the last six months or so, but it’s an interesting question. So there’s a lot of complexities around this dance of, are their optimal ways of combining these things too?
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
Tending to obstruct or harm.
A class of hallucinogenic substances whose primary action is to alter cognition and perception, typically as serotonin receptor agonists, causing thought and visual/auditory changes, and "heightened state of consciousness." Major psychedelic drugs include mescaline, LSD, psilocybin, and DMT. Psychedelics have a long history of traditional use in medicine and religion, for their perceived ability to promote physical and mental healing.
A small molecule that functions as both a neurotransmitter and a hormone. Serotonin is produced in the brain and gut and facilitates the bidirectional communication between the two. It regulates many physiological functions, including sleep, appetite, mood, thermoregulation, and others. Many antidepressants are selective serotonin reuptake inhibitors (SSRIs), which work by preventing the reabsorption of serotonin, thereby increasing extracellular levels of the hormone.
A class of drugs that are typically used as antidepressants in the treatment of major depressive disorder and anxiety disorders. Some of the drugs that fall under this classification include: Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil, Pexeva), Sertraline (Zoloft).
The junction between one neuron and another or a gland or muscle cell. Synapses are critical elements in the transmission of nerve signals. Their formation is necessary for the establishment and maintenance of the brain’s neuronal network and the precision of its circuitry.
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Depression News
- Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF).
- Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014)
- Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010)
- Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013)
- Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021)
