Well, it's the end of the year. We're off the winter solstice. Dr. Malzberg, you know, we're in the dead of winter. There's no light outside. A lot of people get depressed. How about you?
So I have a balcony and this is the first time I've had a balcony. And it turns out there's a lot of sun. It's just cold and you don't see it. So I go outside every day and it's wonderful. With the jacket. You go outside in the cold and the cloud?
There's very little clouds. Okay. It's just cold. It's not bad. It's not much I have to worry about because I'm closer to the equator than most people. All the same, it can get cloudy.
It's one of those things...
It's one of those things I don't do that I tell my patients to do, which is go out even though it's cloudy. You know, uh, the sun peaks through you were saying.
Yeah. My, my advice, this is not, I don't, I, I actually go outside and it's, my mood is better than it's ever been.
Well, very good. If you don't know and you're listening, um, Getting outside in the wintertime, early morning, particularly before 1 m. or some period of time, getting a little sun exposure can be pretty helpful for seasonal depression. That is what I recommend. But that is our topic today, right? Not seasonal depression, but depression. Isn't that right?
That's correct. And my recommendation is I don't do it for theoretical reasons. Like I'm not theoretically happier. Like I feel better in the moment when I'm outside in the sun. And I find that's a helpful thing. If you tell people to run theoretically because exercise is good, they don't do it. But pay attention to how you feel. If you're in the sun, you feel good. So don't do it for theoretically feeling better.
Do it because you'll feel better in the moment.
That's good. It's a little bit of sun worship. You know, it's a classic thing for many humans. You feel good in the sun. I think that's true.
Yeah, and I'm not just bullshitting. I'm in Brooklyn, so it's, you know, sub 30, and I throw a jacket on, and it's nice.
That's definitely too cold for me. So should we be introducing ourselves at least by name at the beginning of these? I feel like we should have more of a ritual, you know? Dr. Fu and Dr. Malzberg. Well, yeah, but we should probably say our own names. Well, you've already said them. So shall we jump in?
Let's jump in.
To the topic today.
So today we're talking about depression and we want to focus a little bit more on the tips and the tricks of the trade. So I'm just going to go question by question and see how it goes. So, you know, I want to get pretty specific rather than, you know, wax theoretical. So I guess to get started, you have a patient who has depression. Depression, what's your typical basic algorithm for starting a med?
What's your first line?
You know, I already have the strong urge and intent to derail you from a set list of questions. Oh, I'm aware. The first thing that I'm going to say is that you can't really talk about depression. As one thing, because depression isn't just one thing. Depression is a symptom, right? And probably the biggest mistake that early career and trainee people in mental health treatment make is that they say, this person feels depressed.
They're talking about depression symptoms. They have major depression, right? And that's just not always the case. Now, depending on your patient population, right, if you're seeing kind of bread and butter upper middle class depression, lower upper class people, yeah, you're going to see major depression, you know, in the single episode sense. But there's just so many variations. Just pay attention to DSM-5. How many modifiers, specifiers that is, they have available for the depressive disorders just tells you that this is not one thing that we're talking about when we talk about depression, even major depression.
Great point. And as you're saying, so depression is a symptom and the goal of a provider is to find out the diagnosis and treat the diagnosis. Depression can be reflection of major depressive disorder, can be reflective of bipolar disorder. A common thing I see, actually a personal anecdote, I have a friend whose girlfriend, he keeps skipping all of our important hangouts because he says his girlfriend's depressed, but she's not depressed.
She has borderline personality disorder as inappropriately diagnosed by me. And... They get they get into fights and then she says he can't go out. And I get upset.
Depression of personality is what I call it. Really should not be overlooked because it very much looks like and even feels like to the patient major depression. But you can tell you based on the life course and the onset and various other factors that it's not quite the same.
Yeah, and so if she were to come to an appointment and she said, I'm depressed, and I said, let's treat your depression, let's use a medication, you'd be missing out on figuring out the diagnosis because even though she would use the word depression, it can be, but it's not a major depressive disorder that you would reach for a major depressive disorder medication.
Yeah, even if there's some kind of benefit... which, personally, I don't see tons of benefit for... depression of personality and use of serotonin-based medications. Even if there's some benefit, it's just not the same kind of benefit that you see in, let's say, a 40-year-old woman who comes in with her first episode of major depression all day, every day, low mood, low motivation, early awakenings, leaden paralysis. You put that lady on a little Zoloft, she's going to start responding right away.
And that's just not the same animal that As a depression of the personality, which is still a depression, still a mind state that causes suffering and problems for that patient. Right. But then you're just going to be spinning your wheels if you're throwing meds at something that is supposed to be treated best by something else.
And you're making a great point. So the point of this particular podcast is treatment of major depressive disorder. So Dr. Fu's main first point, which we didn't intentionally decide this, is make sure you have the diagnosis right. Depression is a symptom. Make sure you're treating the diagnosis. You're not treating the symptom.
Yeah. So I guess the most important thing there would be to say... How do you know it's what we today call a major depressive disorder, which is still not a single entity, but at least it cleans things up a little bit more? Well, you know, there's a concept of differential diagnosis. You've already gone through a lot of good ones there in terms of considerations. I would add a very important one.
If you pay close attention, PTSD and trauma disorders can closely resemble and mimic depressive disorders. Several of even the core diagnostic criteria in the DSM match or at least mimic aspects of major depressive episodes. So be careful. Not everyone is comfortable with or even knows to be disclosing their DSM criteria traumas. And they'll just say, hey, I'm depressed. You know, I'm withdrawn. I'm not leaving the house anymore.
I can't sleep. Well, it sounds like depression or it could be a trauma disorder. So, you know, it's a little bit less important in a sense in that trauma disorders do respond to SSRIs and similar treatments. But it is important because you're not going to address through the psychotherapy and the behavioral component, the avoidance, traumatic remembering and those kinds of issues.
Great point. And I'm going to keep us on. So I want this particular podcast to be about depression, major depressive disorder, medication, tips, tricks, and pearls. So feel free to go on tangents, but I'm going to reel us in if they're going too long. So going back to the first question, you bring up a wonderful point. What is your typical algorithm for major depressive disorder? What's your first line med?
What do you usually reach for?
I mean, I got to be honest with you. I don't love the topic because it's so researched. You know, you can it's just stardy. You can do stardy on this. And I do think it's more important to talk about how to accurately identify a major depressive disorder. But I'll stop diverging. What do I go for first? Easy. SRIs. Why? Well, they're low risk risk. and they are higher efficacy, and the side effect profile is not too bad.
This is assuming that you have accurately ruled out the possibility of a bipolar disorder. Somebody with a bipolar disorder generally can become agitated or worsen if you give SRI, serotonin reuptake inhibitor, So do be careful about that. Again, we are talking, you've confirmed the diagnosis of unipolar depression and nothing else. Zoloft and Lexapro are my favorites. I generally prefer Zoloft. Why? Because more room for titration. You have four steps up to 100 and four steps up to 200 rather than two steps up to 10 and two steps up to 20.
It's just a little easier to work with in that sense and tends to have less medication interactions.
Wonderful. I typically consider there to be four first line in how I practice. I have pretty much four first line antidepressants that I use. As you said, it's Zoloft and Lexapro. If I'm choosing an SSRI, how I choose between those depends on how I'm feeling that day. I also consider Bupropion first line and I'll reach for Mirtazapine for the appropriate patient first line.
Okay. I mean, I love those meds. To me, they're early meds to the Bupro and the mirtazapine. In my mind, I consider them to be augmenting agents. I rarely do the mirtazapine because of the weight gain risk, but if you do have someone where weight gain is not a concern and they have sleep problems, almost everybody with a true major depressive disorder has a sleep problem, then mirtazapine is a great choice.
While Buterin is is a great augmenting choice for people with energy issues and anorgasmia from the SRIs. You can actually give bupropion for anorgasmia in the absence of a mood disorder. It seems to help. You can find some small studies on this. But why don't I do it first line? Well... It's just enough people who respond with too much jitteriness, insomnia, or appetite decrease that they don't want.
But if you have people who are not too anxious, sleeping fine, and eating too much, you know, then Wellbutrin becomes a very nice choice.
Yeah, I agree. You know, I try to typically push for Zoloft or Lexapro first line. But for a patient who doesn't want the SSRI side effects of a little bit of weight gain or sexual side effects, then I am fine with bupropion. And then mirtazapine for a patient where sleep is a big issue and patients either underweight or not concerned with their weight. I would say underweight.
Yeah. then I would choose that med. But I typically push for Zoloft or Lexapro first.
Now, what do you like to do if the first med doesn't work?
I'm having you start out with the questions. I give commentary.
Okay, fine. I'll answer my own question then. You know, it's the classic thing is, okay, you've done the first med and it's not working. What do you do next? Well, what you really have to make sure of is that you're at an adequate dose. And what is an adequate dose? Well, that depends on the person. But you can, as a rule of thumb, say that it's at minimum three quarters of the maximum dose under the FDA approval.
If you're not really there, it's not quite an adequate trial. Now, there's reasons to start switching before you get to an adequate dose, obviously, and that's side effects, right? So if someone doesn't tolerate a medication, then it's time to switch. Don't bother. But if it's tolerated and they're not responding, push the dose. You should push the dose. Be wary. A lot of patients are scared to push the dose for a variety of different reasons.
You want to find out why and talk about it. You know, there can be good reasons to be afraid. And with a little education, they might feel more comfortable. But then if something's not working and it's an adequate dose, you either switch or you augment. Now, I like to augment, but really, the research does not show superiority of one approach or another. You can switch or you can augment.
Yeah, so you talked in abstract terms about what the minimum effective dose is. For my brain, I have Zoloft 50 to be the minimum effective dose. And of course, you mentioned it's different patient to patient. But in terms of expectations across a broad range of patients, Zoloft 50 milligrams is my minimum effective dose for the average patient. And then Lexapro, I have somewhere between 5 and 10 as the minimum effective dose.
Yeah, but I'm not talking about the minimum effective dose. I'm saying that if you have... your sri monotherapy and you are going to say this is time to switch or augment really you should be at three quarters of the maximum dose that's what i'm saying an adequate dose um to say that it's a treatment failure in my book is three
quarters of the maximum now your question was what would i switch to um well would
you switch or augment do you like switch or augment
Again, it depends on the patient. If I had to give an answer, if the side effects are really bad and the patient's having a tough time with it or they find absolutely no benefit, I like to switch. And my instinct is to switch first just to reduce the number of medications. That said, there are cases where you see a little bit of an effect, but... you have side effects or something that makes you not want to push the dose higher, then I would augment.
But I switch is my first instinct.
Yeah. I mean, it's clean. You know, it's a good idea. You keep it simple. Why am I on the augment team? Because I find that one medication usually doesn't immediately treat all the ill effects of depression right away. Most people have sleep problems. Obviously, those sleep problems tend to improve when you've gotten someone to an adequate dose of SSRI. But I like to add a little something for sleep.
And I don't just mean the star D augmenters. I mean things like trazodone, hydroxyzine, gabapentin. See our episode on sleep for more details.
Yeah, and just be careful when you say something like star D because I know a lot of people have read it, but a lot of people listening here will have not read it or know the implications of it.
Well, it's kind of a landmark study where they tested several arms of treatment for depression and would either switch or augment depending on lack of response. And there was even an arm of psychotherapy as well. So sort of a lot of our kind of standard practice for treatment of major depression is at least inspired from that study, if not follows it directly.
Now, we talked a little bit about how do you approach dosing? What do you typically start a patient on? So let's talk about Zoloft and Lexapro specifically. You decide that's the starting medication, average patient that there's no considerations in regards to past history or anything. What dose do you start at? How long do you continue that dose? What's your approach?
It really depends on the severity of the depression and how soon I can see the patient. So let's pretend we can see people in four weeks and it's moderate severity, right? For that, I would probably try to get them to 50 milligrams before the next visit. If you're in a situation where you can't see a patient for a couple months and they're still moderate severity, you may want to give them a little bit more of an option to go even higher.
But really, you should be checking in at least with telephone briefly. to see if they're able to tolerate it. And of course, if you have super close follow-up for some reason, and this person has never been on antidepressant, you might even be able to stay at a rather low dose. People can and do respond to very lower doses of SSRIs. It just sort of depends on the person.
There's no predicting it. What I recommend is find out if they've had anything like it before. And if they have, then you'll know. around what kind of dose they might start to see effects from. And if they haven't, then start low, go slow, but try to follow up soon so that you can address anything that's going on.
Yeah, and I want to make this as specific as possible. So the most common approach I take is, let's say I start Zoloft. What I do is I say, we're going to do 25 milligrams for one week. If you're tolerating it at one week, increase to 50 milligrams. So I usually email the patient after the appointment so they're not overwhelmed with information that they have to remember.
So I'll say, I'm going to prescribe a 50 milligram tablet, break the first four tablets in half, take that for a week, and then assuming you're tolerating it, go up to 50. If you're not tolerating it for any reason, continue. If you're not quite sure, reach out to me and we can discuss. Lexapro, if I'm not in any sort of rush, I usually do the same thing with a 5 milligram.
So I'll say take 5 for one week and then go up to 5. And that's just because I've had a lot of patients have more difficulty tolerating Lexapro if I go 5 to 10.
It's just kind of funny in terms of the approach. I agree, yet when I do the same thing as you for Zoloft, if I'm going to do Lexapro, I get them to 10 pretty fast. It's just it's almost psychological on my part in that, you know, it's I've had problems with getting five milligram tablets from pharmacies locally. So often I don't have that option. So that's why we go pretty quickly to 10.
And in outpatient, I'm not too uncomfortable with getting people relatively, quote unquote, aggressive up titration schedules for SSRIs if I'm confident they don't have bipolar disorder because I warn. I just tell them what to look out for in terms of adverse effects. And it's a medication you can, okay, well, you shouldn't stop any medications without consulting with your physician first. But it's not one where we have a life-threatening withdrawal syndrome, right?
So I will tell patients, for example, with the 5 to 10 on the Lexapro, hey, if you're not able to handle that 10, then just bring it back down and call me.
Yeah, and again, in terms of personal preference, this might just be in terms of – I've lost so many patients to – not lost them in terms of they stopped coming to me. But patients who I start at Lexapro 5 and they just get intolerable side effects and need to stop it, which might have just been a bad person. Can you remember what those side effects were?
um it's been different for different patients the most common is like anxiety and difficulty sleeping which you know could as you say be representative of a bipolar illness response but um typically it's like just a discomfort uh from starting the
medication yeah i find that i i used to get more of that and the further i get along the less i get why because i'm specific in the diagnosis and And if you can detect competing diagnoses, like I said, the bipolar and related disorders and anxiety disorders and somatization type patients, then you avoid a little bit of that adverse effect. Why? Because most adverse effects in most people that have unipolar depression only, it's just nausea and diarrhea.
You're going to get a little bit of that stomach cramping. It's going to last three to five days and get better and come back briefly with each dose increase until it gets better again. And of course, the anorgasmia as the major sexual side effect that can really occur from the medication rather than underlying illness. Uh, the, if you don't know this, the people who might have a little bipolarity, even if they'll never have a real bipolar disorder or have very high levels of anxiety, then yeah, going too quickly on the medication like Lexapro can definitely, uh, cause some reactions there.
Now, um, can you talk a little bit more about how, in terms of dosing, um, you mentioned you're relatively aggressive. Uh, do you have, like, let's say you What's usually your target dose for the average patient?
Well, actually, my target dose is whatever gets them into remission. And I'm a fan of using the PHQ-9 not as a screener, but rather to track symptoms because it covers a lot of the symptoms. It's shorter and easier to administer than something like the ham. or the BEC, and I can do it in a visit. And I don't take it for exactly what it is. I don't just look at the number and say that's definitely what the status of their depression is.
But knowing the patient and knowing their response style, I can interpret the number and also track it over time. So beginning from not every visit necessarily, depending on time, but depending on, beginning from early in the treatment, I start looking at PHQ-9. And if their number drops to close to five, then I'm more inclined to not increase the dose. But as long as their number is, you know, above a 10, let's say, roughly, I'll keep increasing the dose up to the FDA maximum.
Yeah, you bring up a good point in terms of using PHQ-9 or scales because there's so many times that... Patients have been on medication for a while and they say it's not working. Having that baseline and where they're at now is so helpful. And I'm not saying patients aren't aware of their mental state or their depression. I struggle to be able to tell when I'm anxious or stressed because and having those like objective numbers can really you can find yourself in a bind when you have a patient that like you don't quite feel like they're depressed but subjectively they feel like they're not doing so great if you have those numbers they're so helpful to look at and say like hey let's look at how you're doing before and what you're scoring now and then sometimes even that is a helpful process of them saying like yeah i guess i guess now that you think about it i am doing much better i do see the you know the improvement reflected in the numbers
Absolutely. It's a huge part of it. Totally agree. It's, you know, it's not just about patience. I can't remember what I did last week, you know, if I don't take notes. And the process of taking notes and reflecting can help consolidate memories and can bring up other ones that wouldn't have come up without using the screener. And you can get a more nuanced look at someone's actual mental status over the last couple of weeks instead of just going like, have you been depressed?
Well, how much? OK, how's the energy? You know, you get different answers depending on what you do. And yes, being able to reflect on progress or even lack of progress can be pretty helpful, right? Reflecting on progress, showing people how far they've come and also telling people, listen, you know, you've been at this for about a year and you've told me you don't want any medication changes.
I haven't seen any changes in your symptoms. Isn't it about time that we try something new? It can be helpful, too.
Now, I'm curious, when when would you reach for an SNRI?
Personally, I'm not a huge fan. I don't find that they have any efficacy over the SSRIs, and I find that they have slightly more side effects. Even if it's just slight blood pressure increase of the duloxetine, slightly more side effects. Another problem is Effexor is just an awful medication in terms of withdrawal syndrome. It's very strong and uncomfortable. So I avoid that entirely. Now, if my pair mix would allow me to be given Christique more, I would be.
And then I would probably reach for that equally compared to the other SSRIs, but it's not really available for me. So when do I reach for SNRI? Mostly if I see a reason to that is not the depression that comes with the depression. Does this person have a migraine disorder that's been diagnosed and they're not getting enough treatment for? Does this person have a chronic pain issue that they have, there's a good medical explanation for, and that they're not getting adequately treated for?
Then you might as well use a medication that's dual use there.
Yeah, you bring up a good point. I think a lot of practitioners just assume SNRI is a much stronger medication that you should reach for whenever something doesn't work. The number needed to treat is actually pretty big regards to if you use an SNRI compared to an SSRI. And it comes with risks. It comes with side effects. As you mentioned, the Effexor is really, really tough to get off of.
If you look on the internet, you'll see horror stories in terms of patients trying to get off of Effexor and having to go down by one milligram at a time just to try to come off.
Yeah. I mean, it's burned into my head because early in my training, I had a case on consultation liaison service where there was a little old lady who came in from her nursing home with mysterious psychiatric illness, psychiatric medical illness. And I took a careful history. And it just turned out that she decided to abruptly stop taking her Effexor a few days before. And the withdrawal syndrome was so bad it resembled a medical illness to her and to her caretakers and even caused a little delirium.
So I saw that and I thought, man, you know, this based on what people have mentioned patients about the feeling of getting off of Effexor, I'm just not going to reach for it. Not to mention also that you don't even get the norepinephrine effect on Effexor until you get to a relatively higher dose. And so what's the point is what I say.
Yeah. And we both brought up things in terms of clinicians practice, how, uh, formative early experiences are. I had a few early experiences where patients couldn't tolerate Lexapro, so I go slower. You had a formative experience with an SNRI. Those things, for good and for bad, change different clinicians' approaches. That's why you can hear totally different things depending on who you're talking to because people just have My sample size for these medications isn't thousands of patients, especially for not the core medications.
Our sample sizes are pretty tiny, and our early experiences can really paint how we view the medications. Well, I might be at thousands at this point, but yes, early on. No, but you have thousands of effects prescribers?
Oh, sure. For each individual medication, certainly not. Yeah, that's definitely true. Also, a special perfecter because I never use it now.
Yeah. So, you know, in terms of when I would reach for an SNRI, if I saw someone do okay on an SSRI but not great and, you know, they failed too, and when I say failed, like you didn't see a huge dent but you saw a little bit, I think an SNRI is appropriate.
Yeah. Or another SSRI. Don't be afraid to just switch to another SSRI. The mechanisms are not totally the same even theoretically. And one person cannot respond to one SSRI and they can respond to another. So don't forget that. Now, in terms of common ones, we might as well cover them. We have our Prozac, which is nice for people who forget to take their medications because it lasts so long.
And we also have paroxetine, which makes people a little sleepy because of the anticholinergic. It causes a little weight gain, so I tend to not use it.
Yeah, I guess, you know, in terms of how I think about it, I think of Zoloft and Lexapro as my first line. So if Lexapro fails, I switch to Zoloft and vice versa. As you point out, Prozac tends to be a little bit more activating, has that longer half-life. For a particular patient, I will start Prozac first line if, you know, there's a little bit of non-compliance or, I don't know, I think that it'll be helpful to activation.
Then, as you say, Paxil has a little bit of anticholinergic. It also does have a little bit of norepinephrine reuptake. I believe older clinicians really love it for anxiety, if I'm not mistaken.
Yeah, I think there were some studies in the 90s or something that really inspired that. I don't see it as any better than the others. It's more that anxiety, people with anxiety disorders tend to have worsening anxiety and ruminations at night. So if you give them something that makes them sleepy, they're going to help them with that. And it does not have to be Paxil. It can be a little gabapentin, for example, a couple of years old left.
Then Luvox, Fluvoxamine, pretty much I reserve for OCD. I also don't think it's that special for OCD, even though some people do.
It's hard to say. It's got that weird sigma receptor thing that we don't understand. It may even help you with COVID, oddly. The main reason why I don't reach for it frequently is because it tends to be more expensive and often gets rejected for approval. So not really a point doing it unless you're grasping at straws for OCD treatment.
Yeah, and does have drug-drug interactions. Yeah. Yeah, there are other problems with Luvox. And then citalopram.
Oh, I never use Celexa citalopram. There is no point. The active enantiomer is Lexapro, okay? There is no point. Well, there's one point. If you want to prolong someone's QTC, you should use Celexa over Lexapro. If you actually look at the FDA data, Lexapro up to its... 20 milligram dose did not significantly increase QTC. So it seems to be the higher doses of Celexa that were more implicated.
All the same, they recommend you don't go above 10 milligrams in the elderly for Lexapro. And I suspect, though I'm not certain, that Celexa having both enantiomers is a little bit more sedating in some patients. than Lexapro. So that might be a reason to do it. But since I'm Mr. Augment, I don't really bother. I just give a medication for sleep alongside my SSRI. Oh, and about what you mentioned for the sleepiness versus activation, Prozac, etc.
Yes, certain SSRIs are more likely to be either activating or sedating, but it's important to remember that it's completely variable. Patient to patient, You never know what's going to happen necessarily. So I often tell patients, if it makes you sleepy, take it at night. If it activates you, take it during the daytime. Figure out what works for you. It's not terribly predictable.
Yeah, and to play a little bit devil's advocate on your ideas of Celexa slash citalopram, I used to have that very hard line, like, there's no point. It's just, you know, that inappropriate enantiomer. I had a very thoughtful mentor who said she's seen a ton of patients that had tried Lexapro in the past and had completely different response to Celexa. She brought up one case that like the patient felt super uncomfortable on Lexapro, had terrible sexual side effects, and then Celexa worked great for them.
A lot of these meds like even though our pharmacodynamically, it wouldn't make a ton of sense in terms of what we understand. As we kind of said earlier, we don't really know a lot about these medications and there's possible... I don't take that hardline approach of never use Celexa, just as a counterpoint.
Yeah, I mean, I'm not going to freak out on people who use Celexa, but I'm still not convinced. If you applied the same rationale to... brand name versus non-brand name medications, it's still just not prudent, in my opinion. There's just so many other choices that you can use something that's definitively different that's not worth playing around with. And also, in my opinion, a lot of people's different responses at different times to the same medications, and you see this all the time with many different medications, It's more because there's a lot more going on with patients, with people than a single medication.
There's a different context in their lives. There's different mindsets concerning the medication that they're taking at that time. There's different stressors. So that's usually a better explanation than Celexa and Lexapro are meaningfully different.
But I think the lesson I want to get across is I hope people keep an open mind for these things. What we would expect to happen with a medication, you don't always see in patients. And... There will be things. I don't think, you know, a super hard line approach of this medication. I guess I'm just trying to say, like, keep an open mind for what you see.
Don't let your preconceived notions of what you expect from medication to influence what you see. Does that make sense?
Yeah, I totally agree with that. You never know what's going to happen. We don't understand as much as we think we do. And we got to be open to surprises and things that we don't expect and listen carefully to the patients.
So yeah, I think to integrate our two ideas, if a patient had a bad experience on Lexapro, I'm not going to pick Celexa. That said, if a patient tells me that someone else switched them on Celexa and Lexapro is awful to them, I also believe them. So I agree with your approach that I am thoughtful with the fact that I think of Celexa not as great as Lexapro, but I'm also willing to accept patients' experiences if it's counter to what I believe.
Yeah, I totally agree with that. If someone comes in and tells me that Lexus was worth for them and Lexapro didn't work with them, I wouldn't go like, look at you. What are you talking about? It's the same medication. I'm going to switch you back to Lexapro now. No, no, no. That's crazy. Just go with what works. And yes, there are differences between different manufacturers, different brands.
It's a little messy.
Okay, so outside of our first-line medications, how do you think about choosing a next med? You mentioned you don't like SNRIs. What other medications do you pick? How do you think through it?
Well, I think we're really stepping into augmentation territory at that point. And as I already mentioned before, on day one, I will give sleepers. And by that, I mean the non-habit-forming ones that are more likely to support deep, healthy sleep, trazodone, gabapentin, are my first lines for that. If you can't tolerate or have to take something else for some reason, hydroxyzine is a fair choice too. So those I barely consider augmentation, but technically that counts.
Oh, and forgot to mention mirtazapine, which we've talked about already. Now, let's say we've gotten past that point. We have someone at a adequately dosed SSRI or SNRI, and we want to add something. As we mentioned, there is Wolbutrin and Mirtazapine, but you could also consider Buspar. And unfortunately or fortunately, you can also venture into the territory of the second generation antipsychotics, which is very popular in the
, but high risk.
Yeah. Tell me more about your thoughts on the second gen antipsychotics.
So I do think they work, and I don't think it's just that it's people misdiagnosed with bipolar disorder or something like that. I suspect it's just that the second-generation antipsychotics have a lot of different receptor effects, unique ones, that are not present if you have a selective serotonin reuptake inhibitor. So... They work, you know, and what are the lower risk and probably efficacious ones to use? Naturally, the ones Abilify with its unique action at low doses and the ones that have been tested and approved for bipolar depression would likely be expected to work in unipolar depression too.
So that's things like Raylar, Latuda, Fanapt, I believe. There's a couple others as well. I don't like to jump to these. There are so many other choices, including psychotherapy, which is really what you should be pounding the table with before you go to a second-generation antipsychotic. But some patients do respond very nicely to a low-dose one, as long as they're willing to accept the risk of tardive dyskinesia.
Yeah, I have a lot of points I want to make right now. The first point I want to make is this conversation is only about medications. I think we both have a lot of opinions in terms of lifestyle changes, in terms of therapy. I just want to emphasize to the listener, the goal of this podcast is to learn about medications and how to think about them. Not that...
I think lifestyle changes and psychotherapy are part and parcel of treatment. So I just want to make sure you're not... This is just how to think through meds. This doesn't replace all that other stuff. Second thing in regards to antipsychotics... I agree. I don't like antipsychotics. I also think it's not appreciated that a lot of antipsychotics are depressogenic. They can lead patients to depression and long-term aren't great.
A lot of these medications come with really bad side effects, really bad metabolic effects. There's risks of... of EPS, tardive dyskinesia, typically not the lower doses like we're talking about, but they're still there. I don't like antipsychotics personally.
Yeah. I mean, I don't want to frighten people too much. They're extremely effective. We probably shouldn't call them antipsychotics. We should probably just call them something else because they do a ton of different things. But yeah, they're not without risk. You know, a strong medication is strong in other ways too, including with side effects. So use with caution. There are lower risk interventions.
You mentioned Buspar, which I don't tend to reach for. Any other medications? There's, you know, when would you ever pick like a Vilazodone, Vortioxetine, any of these newer ones?
Well, I'd certainly pick them, maybe even Firstline, if they were more available for my Paramix, but they're not. They're perfectly fine medications. I don't find them particularly superior to the SSRIs, the traditional ones, I mean. But, you know, I haven't used them very much. So unfortunately, I can't comment. For cost reasons, I wouldn't go to them first. If people have exhausted a lot of other possibilities in the past, then that would be a better reason to go to them.
Back to Busvar, I didn't used to be a Busvar believer. What I found is that it was probably not being adequately dosed. You can be relatively aggressive with the titration of it. And you shouldn't expect it to give you the moon and the stars. It's got a little bit of benefit. It's more beneficial in some people than others. And don't forget that you can also use it to help combat the anorgasmia again from the serotonin medications.
So yeah, walk me through how you dose and how you think about dosing.
Well, it's funny because if you look at the package insert instructions, you have to... up titrate relatively slowly and over closer monitoring. I have not seen it to produce significant adverse effects in most people. Anything's possible, and so you should give people warnings and tell them to drop the dose again. But Buspar, well, make sure you're giving it at least twice a day. The half-life is relatively short, and you need to reach an adequate serum level.
So twice a day is minimum, you're probably not going to get very much out of it if you're not doing it at least twice a day. Three times a day is usually too much for some people, for most people. Some people are okay with it. So I start usually at 15 and 15, 15 in the morning, 15 at night, and I will step up in increments of 10 pretty much each visit until we can see some response.
Obviously, if you're not seeing any response, then we don't use it. But I'm definitely not reaching for it very often, and most of the time I do it If I'm noticing either sexual side effects or still residual poorly treated anxiety.
So you mentioned 15 BID. How do you increase the 10?
Add it on either in the morning or the night, whatever the patient is most comfortable with. And, you know, so it goes from 15 to 15, 15 and 15 to 15 and 25, for example, and then 25 and 25. OK, and then at that point, you're about 10 milligrams down from the typical FDA daily maximum. So it's only a few steps to get to the whole maximum by taking up to 30 on one of those doses and then both of those doses if you need to.
Awesome. I do want to move to a little bit about side effects and whatnot, but I'm curious, before I do, any other medications that you commonly use that you want to talk about before we jump to side effects?
Well, I know this is supposed to be medications only, but the most important, quote, medications for depression are behavioral activation, exercise, light exposure, and psychotherapy. those are what reach going to get people better if you if they can't go to psychotherapy i will at least have them work through a workbook of some kind you know feeling good slash feeling great from david burns is a very nice one for your classic melancholic depressive uh you know get out of your mind and into your life uh from the act people uh haze is his name is a good one too uh You just have to find one that people are willing to do.
And just even get out of the house 20 minutes twice a week. Do you think you can do that before the next visit? Something as little as that. That will augment your depression treatment more than any single medication if you're only talking about medications.
Yeah, and you bring up a good point where we're really not hammering it enough that you do see providers just try medication, medication, medication, medication. People need to be doing something. They need to have a purpose in life. They need to be – one of the most important things is having small goals and achieving them. You brought up the core things that are low-hanging that we know that are helpful for mood.
Exercise is probably more effective than any antidepressant. The issue, of course, is that a lot of people can't exercise because they're depressed, etc. Sunlight is huge. Relationships, friendships, being social, meditation. These are core things that before just switching medications, medications, medications, see if you can get the patient to
to do those things first. Yeah. And by the way, your initial psychoeducation about the medication is important too. Whatever medications you are picking, this is what I tell people, the medication is not the treatment. It's part of the treatment. And how do these work? You're not just going to start feeling happier. This is not a happy pill. What this medication probably does is that it makes it easier for you to change.
And if you look at the more recent research on how these medications might work, that's probably a the case, or at least that's our best understanding of it for now, it gives you a little bit more neuroplasticity. So I tell them this medication will reduce your symptoms. It does do that. But more importantly, it makes it easier for you to change. So you will have to carry through some changes.
And I want you to pick what those are. And, you know, if you just let the medication do its work, sure, you might feel a little better. But if you really want to be better long term, then let's figure out some things that are going to change in your life. Now, medication wise, though, I think we would be remiss if we didn't talk about some of the older ones that you can go to if people have failed all these previous options, the TCAs and the MAOIs.
Ooh.
Yeah, scary stuff.
Let's get to those. But you bring up a huge point. We are going to do another podcast in terms of just general approach to appointments and therapeutic relationship and whatnot. But yeah, what you said is so, so important. Yeah. How you pitch these meds is going to have a huge impact on how the patient views the meds and what their expectations are. If you're prescribing these things from a stance of, I am a gatekeeper, I give you the meds and this treats your thing, you're going to have so much worse outcomes than if they understand that these things are going to allow them to live the life, to make the choices that will get them better.
It's such a crucial aspect to prescribing these medications.
Mm-hmm.
All right. So, yeah, TCA's and MEY's. Do you want to just start spitballing?
Well, I got to tell you, you can read about the particular characteristics of each TCA, but they're so rarely used that I don't even know them off the top of my head. And I probably use TCA's more than the average psychiatrist today. Obviously, the older psychiatrists, they use plenty of TCA's. They've got a lot more experience, boots on the ground experience. Well, I'll say about the TCA's, be careful.
You know, they have much more side effects. They are dangerous in high doses in QTC prolongation. They make people have anticholinergic side effects like dry mouth, urinary retention, and they're very sedating. but they're also very effective uh they seem to be actually more effective than our ssris and i think it's similar to why we use the second generation antipsychotics because their medications have a lot of different actions in the brain um in terms of which ones are better tolerated again just depends on each person uh probably nortriptyline is a decent one to start with uh But you will just have to figure out which one makes sense to you that you feel comfortable with to start with or that the patient feels comfortable with.
There's so many choices. And then MAOIs, the problem is that you have a risk for a hypertensive crisis with certain foods. Dr. Malzberg, it is tyramine. Tyramine. And in a way, all the best foods have this to some extent at a wine party. If you think about like a Nice board of meats, cured meats and cheeses. There's more than that. You should look it up. What can you do about that?
Well, Selegiline has a patch version where I believe that's less of an issue based on metabolism. Don't quote me on that. We should probably fact check that. But, you know, some patients just don't eat these things anyway, and they're not so concerned about it. Unfortunately, there are some more interesting MAOIs that don't have that interaction that are simply not available in the United States. But if you're listening from outside the
, you might be able to find some options that work for your patients. But the side effect profile and risks of both of these classes, the TCAs and the MAOIs, it really does reserve the use, in my practice anyway, to patients who have failed even the SSRI and second-generation antipsychotic combo.
Yeah, so selegiline is, so in terms of thinking about MAOIs, selegiline is a selective MAOI, and they have a patch which makes it so it's going to decrease the risk of the tyramine reaction. There are three non-selective MAOIs, which if you want to like learn, do you know Dr. Ken Gilman by any chance? No. No. He's got a blog, com. He's probably the biggest outspoken advocate for MAOIs.
He's very passionate that they're under-prescribed and underutilized. That's probably right. I definitely recommend checking out his blog if you ever want to consider prescribing those medications. He is insanely bullish on MAOIs in that he minimizes all the risks that Um, but that said, he's, it's an incredible learning resource. And his big thing is, as you kind of point out, there are food restrictions. They're not life-changing for most people.
And you can get around them without major changes in, in your lifestyle. Um, the, the tyramine foods with containing high tyramine might be overstated than what, or is overstated compared to like what we learn in medical school. Um, But yeah, he views these medications as like point blank, the most effective antidepressants and thinks that we reach for other medications. We keep switching other medications when these patients deserve a trial of MAOIs earlier in the treatment algorithm.
Yeah, there is an argument that if you failed to serious trials of the standard treatments that you should begin to reach for TCA's and MLI's. That is an argument. Do I practice that way? I don't personally, but I also rarely get to a point of failure because of how particular I am about diagnosis and other non-medication treatments. Now, there is one more class of medication that many psychiatrists do use off-label for depressive disorders.
that I would wag a finger at. Do you know what I'm thinking?
Oh, boy. And yeah, actually, I agree with you with the MAOIs. I don't prescribe them that often, but I do think they are a great option for patients who have failed a bunch of treatments and who you feel like you have the right diagnosis. If you do want to learn about them, com. I'm not getting paid by Ken, but yeah. Maybe you should be. medications that are used.
I'm assuming you're talking about benzos.
Oh, no, no. Benzos are, I don't see any independent efficacy in depression, even though they're being given a lot. Some people like to give a benzo early on to help with the anxiety. Amphetamines. But then, yes, some people like to give a benzo or set of hypnotic early on in the initiation of SSRI. in order to help with the anxiety of initiating that. Some patients will need that.
I find that proper psychoeducation and giving a sleeper is adequate. You do not need to give people a benzo. But yes, some people do give stimulants, psychostimulants for depression.
And you have thoughts.
I do. I don't approve of it. Why? It's symptomatic treatment. It doesn't seem to we don't see a lot of evidence for long term effects. Anyone that takes a stimulant will feel better. You take away that stimulant, they will feel more depressed. That's just kind of how they work and don't quite understand why. But the risk is a little too high, and I don't see enough clinical benefit from it.
Now, people that have a lot, a lot of energy problems, quite responsible, well-engaged in the rest of their treatment, there is a little argument, maybe an off-label risk. modafinil or low-dose psychostimulant could help. But all the same, medications are not supposed to be there to be giving a specific transient effect. The purpose is to bring the patient forward in their treatment progress.
Yeah, and I agree. I do have a lot of patients where there's a huge pull to reach for a stimulant. But I agree that it's really diminishing returns. It's one of those things that you say the patient's going to love the first few doses. But thinking long term, you know, it's really catching a patient in a bad cycle. And I agree. I tend to not like to use them.
Yeah. The main exception for me is geriatric depression coupled with more apathy, abolition. That is probably a product of something more neurocognitive. You know, a little light dementia or even full dementia where there's a lot of abolition, apathy, low energy. Add a little stimulant. That's okay. There's something more neurobiological going on.
Yeah, and I, you know, in terms of other options, I would want to talk a little bit more about TMS. I think we should have, do you know Dr. Owen Muir? I know the name. Frontier psychiatrist. He's super bullish on TMS. I think we should try to get him on as a guest.
I mean, great choice. Great choice along with ECT for very serious cases. But TMS, of course, better tolerated. Most people aren't as afraid of it. Probably more available by far than ECT these days, I would think. Yeah, I've had patients who had nice response from TMS. And it's just like any other treatment. Some people get a nice response. Some people don't get any response or can't tolerate it.
But definitely something in the algorithm to refer out to if you don't personally have practice with a TMS machine.
Now, before kind of moving on to those bigger guns things, I do want to talk about side effects from our most commonly used antidepressants. And if you have any tips for managing those side effects. Yeah. You know, ones that I commonly see, weight gain, sexual dysfunction. You talked a little bit about the BUSPAR tip, which is great. Bruxism, you see a decent amount with the SSRIs. Any thoughts in terms of things that you've seen helpful for managing those side effects?
Only certain of those side effects do I have advice for. Weight gain, the best advice is to avoid weight gain inducing medications. Avoid weight gain inducing medications. Prevention is the best strategy there. Now, don't get me wrong. Some people also begin to gain weight, even on the medication that treats depression that does not itself cause weight gain. Why? Because a lot of people lose their appetite when they're depressed.
And if they're chronically depressed, they're not eating. And then you begin to treat the depression and they begin to return to previously existing unhealthy eating habits. We are Americans. Everybody has unhealthy eating. I have unhealthy eating. So you might have to do some basic doctorally education about how to eat more healthily rather than eating automatically. That's an episode for a dietician. For sexual side effects, main ones, buspar and bupropion.
Those are going to be most helpful. and otherwise switching of the medication or lowering the dose are pretty much your choices. You can find certain lists where people speculate on or draw data from trials about which SSRIs are more likely or less likely to cause sexual side effects, but in my experience, it's just quite individual. Now, the bruxism, tooth grinding. You know, Honestly, probably the safest thing would be a mouth guard, which would be quite annoying, but it would protect your teeth.
You could consider maybe using a sleeper of some kind. I have no evidence for that. Maybe a gabapentin or a trazodone. But who knows? Maybe you're just sedating the patient so they don't notice the teeth grinding. Probably best thing to do is switch or to use a mouth guard.
Yeah, I think it might be helpful to have the – like let's say a patient is experiencing bad bruxism and the medication is super effective. So switching isn't really the step you want to take. Have them talk to their primary care doctor. I have seen recommendations for abuse prone. I haven't anecdotally seen it work. Yeah, a lot of that is, as you mentioned, wearing a mouth guard and then discussing risks, benefits of continuing the medication.
Yeah.
And of course, the really most common side effect, the nausea, diarrhea, stomach cramping, it's transient. So if someone's very sensitive to nausea, you could even consider giving some undansetron early on. But most people can, they're fine with it. It's not too bad. And it goes away after a few days.
Have you done that? Are you giving patients undansetron?
No, I haven't needed to do that. But I know people can do that.
Yeah, I have the same experience. And whenever you're kind of, we're talking about expectations are really important. It's always a balance of giving patients information about the medications and then causing a potential nocebo effect where if you say, oh, the nausea is going to be awful, then the nausea will be awful. It's always a tough balance to strike because it's important that the patient understands all the information about the medications, but it's also important that you don't push them to experiencing things
Your level of belief and anxiety about medications matters. It comes across to patients. Just try to be as reasonable as you can as far as that goes and try to stay positive. You can't benefit from something you don't believe in. Your mind will work against it. That's just how it would work.
Yeah, and in terms of kind of your point, the psychoeducation that I provide with the nausea, anxiety, early side effects of the medications, I say, listen, there are certain side effects that they're going to be the worst that they're going to be the first dose you take, specifically the nausea, the GI upset, maybe feeling a little bit uncomfortable. I expect that to get better over the week.
Most patients don't report big complaints after a month. Yeah. So if you experience those side effects and they're tolerable, try to push through it. I expect it to diminish. And then I say there are side effects that if you do experience them early on, we don't expect them to improve. There I'm thinking the sexual side effects. It's not something that's going to improve with long-term treatment. And if there's any sort of emotional blunting, that's not something we would expect to improve.
With the weight gain that you had mentioned, I do feel even if the patient is trying to lose weight, there does seem to be some mild metabolic changes. If I'm not mistaken, the data shows like on average, patients going to gain five pounds over a long term treatment. um i do find even patients that are trying their best implementing changes they can gain five pounds that are really tough to come off of and when they come up i mean
anyone can gain weight but i'm going to point it again to most of this country has eating problems and dietary problems and it's kind of baked into our society itself i'm not convinced that it's the medication i think it's from the treatment effect again loss of appetite large part of depression for most people to have a major depressive episode so it would make sense that treating it would increase in appetite.
But yeah, you know, if there's something that seems to be more related to the medication, if you believe that, probably the best choice is to augment with Walbutrin. You know, it can be used independently to lose weight.
I disagree. I do think, because I've just seen too many patients come off of SSRIs and lose that annoying five pounds. So, you know, in terms of how I, in my head, I think it's a small, for the average patient, it's a small amount of weight that they do see an increase. That's on every patient. And in terms of the cycle that I provide, I say on average, we see about a small weight gain over a long period.
There's patients who gain a lot of weight and there's patients who lose weight. I do think that there is some metabolic changes that occurs just because I've seen so many patients stop the Zoloft, stop the Lexapro, and then those five pounds come off.
Yeah. Check their anxiety and threat salience if we can. We should do a study. I think you're just more keyed up.
Next important question. How long do you treat for?
Oh, well, the classic is, of course, treat to remission and then at least a year before you make some changes. That's not really data supported. It's just kind of prudence because what we do know is usually even if you treat to remission, an early stop or decrease can seems to can it can result in a return of depression. And let's not talk about the data. Let's just think about it in terms of quote-unquote common sense, right?
Like I mentioned, the medication isn't the treatment. The medication helps you change. If you yourself have not made certain changes in your thinking, in your feeling, in your relating, in your behaviors, then getting off the medication early may just bring you back to where you were. You would want to make sure that the depression's gone and that you're also implementing all these changes in your life long-term before you try to some slow and careful changes and trying to get off the medication.
Yeah. And, uh, I, I work with a lot of patients that don't want to be on medications and are hesitant to start an SSRI. Um, you know, some, some important facts that might dictate these things. I, it is important to know that probably half of depressions are one episode depressions and half of people who have depression are going to have chronic depression that they're going to have recurrence if you come off the medications.
Um, Um, typically what I do is I say, listen, as you said, we, we get you in remission. Um, usually from there, I start the clock and at six months we start having the conversation of what is our next steps. Um, so if you've been in remission for six months, we start to engage in the dialogue of do, what do we think? Do we want to continue this med?
And I use the patient as a guide. What are their experiences? At six months, you'll see patients say, you know, I want to get off this medication. You'll see patients who say, listen, I started this medication. My life turned around. I want to continue it. And I tell the patients, we use your experience and your desires from starting the medication as a guide for what we do next.
Yeah, definitely should be patient guided. But I would say, yeah, six months would be my minimum. I prefer a year, but again, totally not database, right? So go off of what the patients want and ask them, what have you changed about yourself, about your life since starting treatment? Do you think you'll be able to stay with that? And don't be afraid to be on the medications, but helps you.
The purpose of this is to improve your life, not to arbitrarily be on the medication or not be on the medication.
It might be partially data-based because my understanding of it, which might be wrong, is risk of relapse if you were to pull it off. And six months seems to be a general number where the risk isn't huge. Like if you pull off at three months, the chances of relapse is super high. If you pull off at six months, you're talking about a smaller risk of relapse.
Right. So yeah, there, yeah, it's about the risk of relapse does get higher or lower depending on when you do it. But I mean, let's be frank, the fact that we pick six months or a year is arbitrary and based on our calendars. That's what I mean. You know, it's, it's, it's not a hard and fast rule. It's just a guideline.
Yeah. Um, all right. We talked about a lot of different things. Um, anything else that you think is, is super important or a topic we should go into that, uh, is kind of the core bread and butter of antidepressant medications?
Well, I think it's probably worth mentioning that there's a lot of hype in certain areas of the internet or of society that feel like SSRIs, antidepressants, Or any psychotropic medication are just super scary medication that completely changes how people think and feel. Now, obviously, they have some effects on your brain functioning. We wouldn't be using them at all, right? But the fact is that it's less a problem, I think, about the medication itself and more about selecting the right medication for the right person at the right time.
And that's why the diagnosis, as I mentioned at the beginning of the episode, is so important. Why do some people get worse than antidepressants? In my opinion, it's mostly because they have some kind of a more bipolar disorder type condition and experience antidepressant-related agitation and sleep problems. That's probably, in my opinion, why we see the increased risk for suicidal ideation in people under the age of 25 on antidepressants.
Because some percentage of those depressed teenagers and young adults do not have unipolar depression. They have something closer to a bipolar depression.
Now, you bring up a good topic in terms of, you know, people being hesitant for the SSRIs. And, you know, I think it's those early appointments where you're developing and we're going to do another episode on, you know, relationship and, you know, with the philosophy of treatment. But I find that Developing a good rapport and a patient that trusts that, you know, they feel that I'm trustworthy.
We have a good relationship. That's probably infinitely more important. It's more important than the nitty gritty of the medications you pick. And when I have a patient who trusts me, who thinks that we have a good relationship, that they can rely on me. the treatment goes so much better. I see less side effects. I see better response to medications. And all that stuff is, the relationship is occurring at all times during the first appointment.
Patients like to know that you have their best interest in mind, that they feel understood. Another thing, as I mentioned, I work with a lot of patients who are hesitant about meds. them knowing that I have no agenda for them to be on meds or not be on meds, and that my only goal is for them to live the life that they want to live. My goal is not be on medications.
You know, I think that stuff comes across very through... It comes across in my interaction and how in subtle ways in terms of how I'm talking to them.
And yeah, that's a really important point, because a lot of people are already trained to expect that you're there to throw a medication at them. That's why they're seeing you. Right. And if therefore, if you don't take active steps to show that the treatment process is more than the medication, then that's the natural assumption. I don't blame patients who think that that's what you're there to do unless you show otherwise.
So we have to show otherwise. We have to show that the treatment is the engagement in the entire process and the changes that they make and not the pill.
yeah um and that's why the relationship is so important and you know these pill mills popping up that go through the algorithm and send you medications uh i think
hymns has one where you know everyone has one i saw an awful one recently there was one on reddit uh it was a reddit ad for a company that promises to treat your anxiety and performance anxiety it's literally a telehealth company that hooks you up with a doctor to talk about whatever you want to talk about, and then give you propranolol. Propranolol. Yeah. Okay. Something that you can get from any primary care doctor and they got a specialty telehealth company for now.
It's ludicrous.
Which can, beta blockers can worsen depression, fun little, you know.
Yes. Yes, they can.
And, you know, I think that's important to bring up because for patients out there that are searching for the right medication for them, it's much more important to have a strong, good relationship with a practitioner who has your best interest in mind than searching out the right medication for you.
Yeah. Don't look for the right medication. Look for the right treatments. Beautiful. Anything else? I think that'll do it. We are coming to the new year. We'll be out of the winter. Look towards the future, everyone. Look towards the future.
That's beautiful. Thanks a lot for listening.