S1 Episode 6: Climbing Out of Depression

Dr. Stieg talks to psychiatrist Richard Friedman, MD, about depression and PTSD: How they are different from sadness, how the brain actually changes when someone is depressed and when they come out of it, and how therapy and medication work. Plus… identifying those at risk for suicide, and getting them help.

Dr. Stieg: I’m back again today with Dr. Richard Friedman, Professor of Clinical Psychiatry and Director of the Psychopharmacology Clinic at Weill Cornell Medical College. He’s also an op-ed contributor to the New York Times. Last time we met we were talking about fear, anxiety, and I’d like to change the focus now and talk a little bit more about depression. We all get sad. What’s the differentiation between sadness and depression and when does it become a clinical disease?

Dr. Friedman: So everybody feels sad and everybody gets upset and usually it’s because so

mething happens that is upsetting. You know, you have a loss, you lose your job, you break up with somebody you love, your house burns down, you know there’s stress. And the difference between a normal reaction to loss is sadness, but depression is something different. Depression is a syndrome. It’s a syndrome in which somebody develops a pervasive sense of loss of pleasure. And the core thing about depression that most people don’t understand is it’s primarily not about feeling sad. It’s about feeling the absence of pleasure and the absence of feeling. It’s a negative state that has these associated other symptoms like change in appetite and difficulty sleeping in loss of libido. And then one thing that sad people do not experience and that is a loss of self esteem. People who are sad basically can tell you, I’m sad because this happened and I’m sad because that happened. And if you ask them, yeah, but do you feel critical or bad about yourself? The answer’s no. There’s nothing wrong with me. The world did something, I lost something, I feel fine. My self esteem is preserved. People who are depressed have an impairment in self esteem. They lose their self esteem and they think that things are never going to get better and they have distorted thinking and then they have suicidal ideas and they make suicide attempts and commit suicide.

Dr. Stieg: I’m interested when, last time we spoke about anxiety and fear, and addiction — you mentioned the need for pleasure and the dopamine. And now again, when you’re talking about depression, there’s this absence of pleasure in somebody’s life. And I’d like to link it to the concept of boredom and how we deal with boredom. And as I was reading about boredom, I was thinking, I love being bored. I liked just the absence of anything. And there’s just this feeling of being alone and quiet. And I don’t think enough of us know how to be bored. But when I was reading about it, it also went into there’s some loss of pleasure and that’s why the person is bored and they’re waiting. They don’t know what for, but they’re waiting for something to happen, which is kind of like what you’re saying about depression. You know, it’s, these are the world’s fault. Explain that to us.

Dr. Friedman: The difference is the person who’s just bored, because at the moment there’s not a lot of stimulating things happening in their life and there’s a kind of pause. They can experience pleasure and excitement when they’re put, where they put themselves in an environment where they’re stimulated. Whereas if you’re depressed and normally you’re an excited, happy, enthusiastic, engaged person, I’ll put you in those situations that usually you love and they’ll fall flat. You won’t feel excited and you won’t be able to climb out of that bored, depressed state because something has changed in your brain to make you unresponsive to it. That’s the difference.

Dr. Stieg: Are we then saying that everybody that is clinically depressed needs medical management?

Dr. Friedman: No. Actually most of them will get better spontaneously.

Dr. Stieg: And how long? How long does that take?

Dr. Friedman: It can take a couple of months to get out of a depressive episode, so you wouldn’t want to leave it untreated. But the natural course of depression after first episode is the majority of people will get better.

Dr. Stieg: And during that time they should undergo what?

Dr. Friedman: So the fact that the depressed brain is biologically different than the non-depressed brain doesn’t mean that you need a biological treatment to get better from depression because your brain is responsive to lots of influences like talk therapy, which is very effective in treating depression. But you know, we know that that changes your brain also. So does exercise. So does travel. So the brain is very open to influence and the depressed brain is open to lots of influence. So if I get depressed people to exercise and I get them to talk about what’s bothering them, they feel better. And if you actually study people who are depressed with different types of treatment, when they get better, the brain changes in surprisingly similar though not identical ways to treatment.

Dr. Stieg: Are there, functional MRI scans that have been done that demonstrate the brain is, has plasticity and can improve structurally with either talk therapy or a biologic therapy?

Dr. Friedman: Yes. So there are imaging studies showing that the changes from talk therapy and the changes from antidepressant therapy are very similar though not exactly the same. And so these are blood flow changes. So they’re functional, not structural, and they converge and they look pretty similar, but they’re not exactly the same, which is probably why talk therapy and antidepressants are in combination, complimentary and synergistic.

Dr. Stieg: Is meditation beneficial for a patient or a person that has a predisposition towards depression?

Dr. Friedman: Well, we know more about the benefit of meditation, I think for anxiety than for depression. Clearly it’s effective for anxiety. I don’t think it’s actually been studied well for major depression.

Dr. Stieg: I was just thinking about it because of the known positive impact on structural changes in plasticity within the brain with meditation. I was curious whether there was any data on that. Every patient I see, they always worry about, “Am I going to pass this on to my children?” What component of is genetic? And if I’m depressed, how much do I have to worry that my children are going to be depressed?

Dr. Friedman: The heritability of depression is actually small. Most people who are depressed don’t have a parent with depression. You know, I always think this is funny. When people go out and they get the 23andMe and they get all the genetic markers and they have a risk factor for disease X, Y, and Z. You know, the little secret is most of those risk factors, especially with behavior contributes so little to the overall risk that most people with those factors don’t have the disease. And most people with the disease may not even have those risk factors. I would say. You know, if you’re somebody with depression, the odds that your kid has depression are maybe slightly higher than the general non-depressed population, but it’s not that high.

Dr. Stieg: You’re a depressed patient and you’ve seen your psychiatrist, you’ve done talk therapy that hasn’t helped you try the serotonin reuptake inhibitors and that hasn’t helped. Is there anything new coming out that’s being used to treat depression?

Dr. Friedman: Yes. So there are a new class of drugs starting with ketamine. Drugs that actually work on a new neurotransmitter in the brain that the current classes of drugs don’t touch. And that’s glutamate, which is a different neurotransmitter than all of the current available antidepressants target.

Dr. Stieg: So we’ve gotten back to the uh, glutamate re-uptake inhibitors. We found some new drugs?

Dr. Friedman: Ketamine is an old anesthetic, right? And it has very strong, very rapid antidepressant effects.

Dr. Stieg: Transcranial motor stimulation is quite interesting and it’s being used in the treatment of depression. What is it and does it really work?

Dr. Friedman: Right? So transcranial magnetic stimulation involves just putting a magnetic field over the scalp with a magnet and then inducing an electrical change in circuits in the brain that are involved in mood and it doesn’t involve being unconscious and you don’t need anesthesia and has almost no side effects except maybe a slight headache and it is effective. It’s not as effective for depression as—

Dr. Stieg: 50% of the time? 75? What, do we have any numbers?

Dr. Friedman: Most people who get it tend to have failed, you know, lots of treatments. So the response rates are lower than you would expect. Maybe 50%.

Dr. Stieg: Cause of the hardest of the hard cases?

Dr. Friedman: You’re dealing with resistant patients so they may be lower. It’s not as effective as the most effective treatment for depression, which is ECT or electroconvulsive therapy.

Dr. Stieg: Which is much more involved and — what are the side effects of that?

Dr. Friedman: The side effects of VCT? You know the side effects of the brief anesthesia, you get some memory loss for events right around the day you have the treatment.

Dr. Stieg: But not permanent memory.

Dr. Friedman: No, no, no, no. There’s no evidence that there’s permanent memory loss, in ECT.

Dr. Stieg: And and is that a really effective therapy? Or again, is it, are we talking about the hardest of the hard cases?

Dr. Friedman: It is the most effective treatment for depression.

Dr. Stieg: Do you use it early on in a therapy then or not?

Dr. Friedman: Yeah, we use ECT for people that have failed several antidepressants, so it’s for refractory patients.

Dr. Stieg: Post traumatic stress disorder is also a very popular subject right now with, with the veterans coming back and it’s a complex psychological disorder, but one part of it is also also involves depression in the PTSD patient. Do you treat the depression separately or do you treat the entire syndrome for the patient?

Dr. Friedman: So people that have PTSD and depression are particularly complicated to treat and hard to treat because you can’t treat one without the other and they often go together so you have to treat them both and the treatment for PTSD is never just a medicine because PTSD is basically a form of fear learning that’s gone awry and in order to learn not to be afraid you need therapy, you need some form of psychotherapy because you’ve had to learn something.

Dr. Stieg: Treatment for PTSD involves some talk therapy but also eye movement desensitization and the numbers that I was seeing for that actually astounded me, that they’re effective 80% of the time. Is that true?

Dr. Friedman: There seems to be no question that EMDR works. We don’t know how effective it is and whether it works in people who have more severe PTSD. And it works by moving the eyes in a certain direction while you get the patients to talk about these upsetting experiences they’ve had and somehow they have some change in their brain and their experience so that they don’t have the same symptoms they had before.

Dr. Stieg: But it’s effective.

Dr. Friedman: It’s effective, how effective it is and for what forms, how severe the PTSD is. We don’t actually know.

Dr. Stieg: Your therapeutic goal with post-traumatic stress disorder is what?

Dr. Friedman: The goal is to teach the person that the thing they’re afraid of is no longer a danger and they should learn to be unafraid. The problem in PTSD is that somebody has learned that a previously safe situation is now dangerous. So if I were mugged on the street — I’ve never been afraid of being in the street, but when I develop PTSD, I’m now going to be afraid to walk out on that street because it’s associated with a terrible thing that happened to me. So in treatment, you’re going to take me and bring me out to the street in a safe setting and show me actually the street is no longer a danger and you have no reason to be afraid of it. And what you’re going to be doing is teaching me that I have learned an association, which is now incorrect and I’m now going to feel safe on the street. But what you didn’t do with this treatment is get rid of my old association. It lives in my brain alongside the new safe memory you gave me. So the problem is that exposure therapy gives new safe memories but cannot touch the old bad ones.

Dr. Stieg: How do we go about reconstructing our memories?

Dr. Friedman: Since the old bad memories are in the brain and they live aside the new ones that we’ve given people, the two are in competition with each other, which leaves people with PTSD always vulnerable to being retraumatized. So can you take an old bad memory and alter it? That’s what you want to know. And we know there’s some early evidence that you can interfere with memories and you can actually alter them. Experiments were done, let’s say with people who have spider phobia — arachnophobia. And what happens is you can actually interfere with the link between the thing the person’s afraid of and their emotional reaction. So they can actually be around the spiders without being phobic of them. They will still remember that they were afraid of them. So you’re not getting rid of the biographical information. They know that they once were afraid, but when they see the spider, they don’t have a fear response anymore. That’s possible to do.

Dr. Stieg: That makes sense to me. Cause I was thinking that once a memory is in your brain, unless those neurons die, it’s going to be there. So I guess it would seem to me that, you know, through plasticity, how are we reassociating these connections so that instead of being a terrible response, you can actually cope with the situation.

Dr. Friedman: Yeah. Because you probably can alter the link between emotions and the actual, you know, memories. But some trace of the actual learning is going to be there.

Dr. Stieg: That leads us into, for me, a sad subject, as we talked about depression, suicide is the worst manifestation of that. What is happening there?

Dr. Friedman: Well, what’s happening that people who are depressed, severely depressed, feel hopeless and they actually don’t believe they’re ever going to feel better. And so they’ve got a distorted view of themselves in the world and they often develop suicidal feelings and thoughts. And about two to 12% of people with depression will go on to kill themselves. And considering the rate in the general population is about 12 and a hundred thousand. Having depression is a very big risk factor for suicide.

Dr. Stieg: In terms of the cause of death, you know, that’s a fairly significant number. What global number do you quote when somebody says how many people die of suicide related to depression? Is it a million a year or?

Dr. Friedman: So the lifetime risk of depression, let’s say, just pick 10% so now you’re talking about, you know, 30 million of whom only a small number have severe depression cause severe mental illness is rare. So it’s a much smaller number than that.

Dr. Stieg: My loved one says to me that she’s depressed. When do I need to be alarmed about the level of her depression?

Dr. Friedman: Yeah, well if you have a loved one who’s depressed, you want to get them help and you also want to know whether they’re feeling or thinking about suicide. So people should not be afraid to ask that question. A lot of people are afraid that if asking the question is somehow going to encourage people to do something they wouldn’t do. People are afraid to ask or talk about suicide will somehow implant the idea. That’s incorrect. We know that’s wrong.

Dr. Stieg: Are there environmental factors that play into suicidal rates changing?

Dr. Friedman: So the suicide rates have been going up and down for the last 100 years. So what most people don’t know is that although the rates have gone up in the last few years, they’d been much higher in the last 100 years. So the highest point was right after the Great Depression. The real problem is that the suicide rates have not dropped over time. Like every other major illness that kills people, like the rate of heart disease and stroke has gone down. Why?

Dr. Stieg: With the advent of all your drugs you haven’t been able to change this? *laughs*

Dr. Friedman: Cause you know what it is? Because we threw a lot of money at these problems and we started treating them. We have statins, we have anti-hypertensives. So with depression, yeah, we have antidepressants, but it takes more than an antidepressant to get people better and keep them better. So the problem is, you know, as a public health problem, we’ve done almost nothing to change the rate of suicide in the United States in the last century. We need to treat people, we need to go after depression the way people declared war on cancer. Declare war on depression.

Dr. Stieg: Is there a link between if I’d manifest signs and symptoms of depression when I’m 15. Am I more likely to have a serious depression when I get to be 50 and maybe commit suicide versus, I’m 40 and I start getting depressed.

Dr. Friedman: The curious thing about depression is you can have a chronic depression that’s very treatable that just hasn’t actually been evaluated or treated and you get better within weeks and also so chronicity and difficulty in treating or getting better or not related. Or you could have an acute depression, which is super hard to treat. So the amount of time that somebody has been ill isn’t actually a good predictor of whether they’re going to get better. There are other factors of the depression.

Dr. Stieg: Are there forms of depression? I mean we as doctors like to come up with classifications for everything. Number one, are there forms. And number two, are there particular forms that are worrisome to you as a psychiatrist for leading to suicide?

Dr. Friedman: Yes. The most serious form of depression is what we call delusional depression or psychotic depression where somebody doesn’t just feel depressed and feel worthless and hopeless, but they develop delusions and they have thoughts that say, people are going to kill them or they’re going to die of malnutrition, or they have delusions of poverty. That could be a very wealthy person and basically say, my life is over because I’ve lost all my money. And you look at their bank account and you say, what are you talking about? You still have a job. They have an idea which is false and not responsive to reality testing. That’s a very severe form of depression which is associated with a high risk of suicide.

Dr. Stieg: Are there new drugs coming that will help us treat depression and hopefully diminish the suicide rate?

Dr. Friedman: Yes. There are a group of new drugs that target a new system of the brain, the glutamate transmitter in the brain that have an advantage in that they work faster than the older drugs. And they have specific anti-suicide effects, which is distinct and interesting.

Dr. Stieg: And this would be, we could use this across all populations, children, adults.

Dr. Friedman: Well we don’t know yet, aside from adults with failed antidepressants cause those are the ones who are now getting it and being studied. So we don’t know yet whether kids will respond or adolescents with depression will respond.

Dr. Stieg: As a psychiatrist, I, I’m sure that depression is one of the major things that you have to cope and deal with on a daily basis. What is the key message that you want to get out to people about number one, recognizing it and number two, helping somebody that has it.

Dr. Friedman: So I think the most important thing to realize if you’ve got depression is you’re in good company. It’s extremely common. It’s also very treatable that if you’re depressed, even if you believe that things aren’t going to change and you’re not going to get better, you’re wrong.

Dr. Stieg: You’ve got a treatable illness, and the trick is to get them to understand and believe that, right? Yeah. Yeah. You just beat them over the head. Dr. Richard Friedman, thank you so much for spending this time talking with me about both suicide and depression, and I hope that we’ve provided some insight into the treatment of these diseases.

Dr. Friedman: It’s my pleasure.