Antidepressant Tier List: Psychiatrists Rank Depression Medications for MDD

Summary

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Psychofarm Podcast: "Antidepressant Tier List – Psychiatrists Rank Depression Medications for MDD"

Date: May 19, 2026
Hosts: Dr. Malsberg (A) & Dr. Fu (B)
Theme: Deep-dive, evidence-based, and experiential ranking of antidepressant medications used for major depressive disorder (MDD)—with a candid, practical, and sometimes irreverent psychiatrist-to-psychiatrist tone.

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Episode Overview

This episode shifts gears from typical clinical didactics and dives into a popular internet trend: the "tier list." Drs. Malsberg and Fu rank antidepressants for MDD, debating pros, cons, quirks, and clinical subcultures related to each. Their candid, sometimes tongue-in-cheek style adds an engaging layer to their expert insights, aiming both to inform and challenge common psychiatric prescribing habits.

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Key Discussion Points & Medication Tiers

1. Ground Rules & Philosophy of Tier Ranking

• Dr. Fu wants a rules-based, “real-life” tier list: “I’m gonna pick the ones that I think are just all arounder best in real life... the ones that I would actually prescribe first.” (04:28)
• Dr. Malsberg prefers a more "feels-based" approach, debating the complexity of real-world prescribing, where efficacy and side effect profiles must be balanced differently for every patient. (03:53–05:34)
• Both agree: Minimizing side effects is key, but “most efficacious” often competes with “best tolerated.”

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2. Stimulants & Benzodiazepines—Firmly in the F Tier

• Stimulants (Adderall, methylphenidate, Dexedrine):
  • “It's not a very good antidepressant… Proper psychiatric treatment is not something that you build tolerance to.” (B, 07:44)
  • “F. Because we're talking about depression.” (B, 10:36)
  • Exception: Very niche use in geriatric apathy (not MDD).
• Benzodiazepines:
  • “They are symptomatic treatments that create habits, build tolerance and stop working. They're not fundamental treatments...” (B, 27:56)
  • Both hosts allow for short-term use in crisis-driven, agitated depressions but emphasize avoiding regular use for MDD. (A, 29:13)

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3. SSRIs—Core First-Line Choices, But Not All Equal

Sertraline (Zoloft) – S Tier

• “Great medication. First of all, you can titrate it on multiple steps… just works. Works pretty great… S tier.” (B, 11:49)
• Preferred for safety (esp. pregnancy/breastfeeding), flexible dosing, and fewer drug interactions.

Escitalopram (Lexapro) – A Tier

• Sought for “purity” as an SSRI but may be less well tolerated due to individual metabolic variance.
• “Lexapro used to be in my S tier… across increasing clinical experience… still a great medication, probably my number two.” (B, 13:09)

Fluoxetine (Prozac) – A/B Tier

• “It's kind of like Haldol… old, high FDA max… can be effective even at low doses… Great for patients who miss doses (long half-life)... but maybe more side effects.” (B, 21:24)
• Dr. Malsberg: “I put it in B strictly—has nothing to do with the medication itself… I get anxious about using Fluoxetine just because I think I've used it slightly less.” (A, 22:59)

Paroxetine (Paxil) – C Tier

• Effective but: “Weight gain, anticholinergic effects… short half life... I cannot rank this one highly.” (B, 33:33)
• “It's sedating. It does have bad withdrawal because… anti muscarinic... bad for pregnancy... and weight gain.” (A, 34:25)

Citalopram (Celexa) – B Tier

• “Basically Lexapro, but makes you more sleepy and it causes you more QTc prolongation.” (B, 36:19)
• Clinical take: Sometimes effective where escitalopram isn’t, but rarely preferred first-line due to side effects profile. (A, 36:53)

Fluvoxamine (Luvox) – Questionable/Niche Use

• “Pretty much only use in patients of OCD... The Sigma did some mysterious ssri. That goes its own way... too many med-med interactions.” (B, 40:24)

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4. SNRIs—Efficacy with Withdrawal & Side Effects Caveats

Venlafaxine (Effexor) – B Tier

• “It works... but withdrawal syndrome..., famously the worst withdrawal… works well, but just be careful.” (B, 43:14)
• Not usually first-line unless comorbid migraines or pain.

Duloxetine (Cymbalta) – B Tier

• “More balanced than venlafaxine, supposedly... little special indications with regards to pain.” (B&A, 47:07)

Desvenlafaxine (Pristiq) – B Tier

• Slightly better tolerability, less drug–drug interaction than Effexor, but otherwise similar. (A, 49:10)

Levomilnacipran (Fetzima), Milnacipran (Savella) – A Tier (Rare Use)

• “Maybe, maybe, maybe actually fulfilling the promise of snri.” (B, 48:29)
• Limited real-world use, often blocked by formulary/cost.

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5. “Atypicals”: Key Non-SSRI/SNRI Antidepressants

Mirtazapine (Remeron) – S/A Tier

• “Despite my hatred of weight gain, I must put Remeron in A class. Oh man, it works so good... Great med.” (B, 50:51)
• Dr. Malsberg: “Spectacular medication, incredibly sedating. Warn your patients they will feel like a zombie (first few days), but this usually gets better.” (A, 51:53)
• Useful for patients with insomnia, weight loss, or prominent GI symptoms.

Bupropion (Wellbutrin) – A Tier

• “Great medication, can give you a pep in your step... beware of using it in patients who have a lot of baseline anxiety...” (B, 55:41)
• “Doesn’t have the typical side effects—weight, sexual, or sedation—but is overhyped for anxiety... Know who will actually benefit.” (A, 55:41)

Trazodone – C Tier

• “Not tolerated enough by most people at high dose required for antidepressant effect... quite efficacious for sleep, not necessarily for depression.” (B, 58:56)
• Beware paradoxical reactions due to active metabolite (MCPP). (B, 60:28; A, 60:50)

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6. Augmentation, Mood Stabilizers & Second-Line Agents

Lithium – S Tier (For Recurrence/Resistant Cases)

• “If we narrowly define major depressive disorder as simply the state of depression… and we take the population… who don’t respond to psychotherapy… over time you are going to see more and more of those people who may have a bipolar depression… Lithium is all the way at the bottom… as it always is in real life.” (B, 17:08)
• Dr. Malsberg: Lithium should be “used significantly earlier” in recurrent or temperamentally loaded depression; low-dose lithium is underused. (A, 19:03)

Atypical Antipsychotics (Abilify, Seroquel, etc.) – Use with Caution

• Abilify (aripiprazole):
  • Initially S tier as adjunct, but: “Even at low doses, the risk of tardive dyskinesia is there... Do not dose Abilify above 5mg if what you are trying to do is treat MDD without psychotic features, do not do it.” (B, 62:33–63:33)
• Seroquel (quetiapine):
  • “Great augmenting agent… appetite and weight gain are significant; it’s hard to get patients off it sometimes.” (B, 64:32)
  • Both: Only for treatment-resistant or properly diagnosed cases, given side effect risks.

Lamotrigine (Lamictal) – Not for Standard MDD

• “Too niche... do not put it up there… S tier med for bipolar, not for MDD.” (B, 71:07–71:53)
• May help with “emotional dysregulation," but not routine for MDD.

MAOIs & TCAs – Deep Reserve

• Both hosts wish there was more room to discuss these—reserved for "true treatment resistant depression."
• “Consider your TCAs and MAOIs if you know what you’re doing.” (B, 72:44)
• “Phenelzine and selegiline patch in A or B tier probably.” (A, 72:57)

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7. Newer/Expensive Agents

Vortioxetine (Trintellix), Vilazodone (Viibryd) – B Tier

• “Didn’t really pan out in terms of the promises… expensive, not particularly more effective than others… something you try if the others are not tolerated.” (B, 65:28–66:33)
• Vilazodone may marginally help with sexual side effects, but not dramatically.

Esketamine (Spravato) – D Tier

• “Works great in a select amount of people, can be life-saving… but probably has opened up the field to more peddling of drugs instead of treatment… only a seven day treatment effect.” (B, 66:58)
• Dr. Malsberg: “So many patients are seeking it out as a drug to ignore other problems… not all patients, but it raises risks.” (A, 68:15–69:24)

Buspirone – B Tier (Honorable Mention)

• “Big fan… relatively well tolerated, efficacious for anxiety/irritability augmentation… seems to help SSRIs’ sexual side effects.” (B, 69:24–70:15)

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Notable Quotes & Memorable Moments

• On Stimulants for Depression:
  “What you feel on a stim… is the euphoria and energy burst and you will build tolerance to that. Proper psychiatric treatment… is not something you build tolerance to.” (B, 07:44)

• On the Challenge of “Pure” SSRIs:
  “Purity is very overrated, both in real life and in medications. I love a dirty drug… that can do multiple things at once.” (B, 15:39)

• On Wellbutrin and Patient Selection:
  “You should be learning patients that respond well to SSRIs versus patients who will respond well to bupropion.” (A, 55:41)

• On Seroquel as an Augmenting Agent:
  “It works great, and anyone who doesn’t care about weight gain and appetite increase… but it definitely causes a ton [of both]…” (B, 65:06)

• Cautious Optimism on Lithium:
  “We have to remember that there are varieties of major depression… agitated depressions… do they respond to mood stabilization? They may.” (B, 17:24)

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Timestamps & Segment Highlights

• 03:00–06:00: Setting up tier list philosophy; rules vs. reality.
• 07:19–11:49: Why stimulants and benzos get flat-out F’d.
• 11:49–16:21: Zoloft and Lexapro—Why they're top-tier mainstays.
• 17:08–20:41: The lithium “statement” and debate on early use in recurrent MDD.
• 21:04–25:45: Prozac’s quirks, pros/cons in clinical use.
• 33:56–36:53: Paxil and Celexa—Sedation, withdrawal, & modern practice.
• 40:01–41:29: Luvox and the “sigma enigma.”
• 42:03–46:53: SNRIs—Venlafaxine, duloxetine, desvenlafaxine: tolerability and withdrawal.
• 50:05–55:41: Mirtazapine and bupropion—the atypical first-liners and key clinical pearls.
• 58:56–61:34: Trazodone and paradoxical reactions.
• 62:33–65:28: Antipsychotic augmentation—the fine line of risk vs. benefit.
• 66:58–69:24: Esketamine, the hype, and clinical realities.
• 72:42–73:27: TCAs, MAOIs, and the importance of diagnostic precision.

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Summary Table – Antidepressant Tiers (Major Depressive Disorder)

(Approximate ranking from conversation – host preferences may vary)

| Tier | Medications (Examples) | Key Rationale | |:------------:|:---------------------------------------------------------|:----------------------------------------| | S | Sertraline, (Lithium for select pts), (Mirtazapine)* | Best blend of efficacy/tolerability | | A | Escitalopram, Mirtazapine, Bupropion, (Pristiq) | First-line in many; specific profiles | | B | Fluoxetine, Citalopram, Duloxetine, Buspirone, Vortioxetine, Vilazodone, Desvenlafaxine | Good options; more side effects or less robust evidence/effect | | C | Paroxetine, Trazodone, Cymbalta | Side effects/better alternatives exist | | D | Esketamine (Spravato) | Rare, highly selected use only | | F | Stimulants, Benzodiazepines | Not antidepressants, risk of harm | | Question | Lamotrigine, Antipsychotics, MAOIs/TCAs | Special, case-by-case or under-used |

*Mirtazapine's position is hotly debated between S/A by the hosts; similarly, antipsychotic augmentation and lithium are S-tier only for select patients.

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Final Takeaways

• Individual patient factors, diagnostic precision, and minimizing side effects remain central to effective prescribing.
• SSRIs and mirtazapine/bupropion are front-line for most, with SNRIs, TCAs, or MAOIs reserved for specific comorbidities or resistant cases.
• Augmentation should be cautious—and antipsychotics/lithium used only when rationale is solid and monitoring robust.
• Newer agents and esketamine: promising, but with significant caveats.
• "Treatment-resistant depression is where personality disorders go to hide." (A, 65:15)
• "The tier list you use for medication should really be tailored to your patient population." (B, 73:04)

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For more, see: psychofarm.substack.com

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Transcript

[A]

Welcome to the Psychopharm Podcast. This podcast is for education and entertainment. It certainly is not medical or psychiatric advice, diagnosis or treatment. Listening does not create a doctor patient relationship with me or Dr. Fu. Your patients certainly don't change your treatment plan because of something you hear on the show. If you're a clinician, do not use this podcast as a clinical reference or substitute for your own training, judgment, thinking and up to date sources. Opinions are our own and don't necessarily reflect any employer or affiliated organization and that you to be detached from reality.

[B]

Good morning, Dr. Malsberg.

[A]

Morning. How we doing?

[B]

Oh, not too bad. I've got a hot new mic. A hot mic, if you will. I don't know if it's going to be any better than usual. I think there was one vote to kill the Ewoks, which I think is pretty cruel but fair. So hopefully this will go some ways in accomplishing that.

[A]

I. I maintain that it's not your. You're not the one at fault. I think it's a production error, so I don't think the hot mic will fix anything, but we'll see.

[B]

It occurs to me that if it's your first time listening, that was complete gibberish and maybe even disorganized speech, which if you don't know the context, speech can sound disorganized. So you do want to be a little careful about calling it disorganized if you're talking to someone with a lot of flight of ideas or delusions because maybe it's not disorganized speech. Maybe they're just talking about something you don't really understand.

[A]

Yeah, and let's not go too into it, but we've got a terrible production team for our podcast.

[B]

You're the production team, right?

[A]

That is correct. It's mostly me.

[B]

Okay. Speaking of disorganized speech, I don't know if we're going to be talking about the medication solution for that today, but I believe today's topic is concerning medications. Is that right?

[A]

So today we will. We're making a tier list for medications. I see YouTube videos all the time of these tier lists. I don't quite understand it. I feel like I'm just slightly above the generation that is on YouTube all the time and knows what exactly these are. But I do see them all the time and we are trying to sell out more and create low tier content.

[B]

Age is just a state of mind, Dr. Malsberg. And you know, I'll be honest, I actually don't know your age, but I always anticipated that you were actually the age for these YouTube tier lists, but that you're just, you know, kind of old soul, kind of a hipster dude who does not get into YouTube of all things except for educational purposes.

[A]

Well, maybe that's just because you don't know my age and let's not talk about it.

[B]

That's rude. Anyway, we won't talk about it.

[A]

Maybe I just have a young sounding voice. Well, let's get into it. I've never done one of these things. I'm assuming you've never done one of these things. I have no idea how it's going to go, but we'll make it up as we go.

[B]

I mean, I've done tier lists in my head for things that aren't medications exactly. I think I've had these discussions professionally about favorite medications. But I think that if you're going to get into a project where you do a medication tier list, you gotta set some ground rules. And I think we can do this in two different ways. It can be a real life tier list. In terms of which medication would you 90% of the time pick first if there is no problems with it? That's one version. And then another version I can think of would be the desert island medication lists. Pretend for some reason you are airdropped onto a desert island and you have to treat 100 patients who are, you know, reflective of the general population of patients. And you only get one medication in each class. Kind of like desert island discs, but with medications. So which rule set do we want to go by or do we want to do both?

[A]

You know, I don't like those rules because there's medications I like that I don't commonly use or medications that I don't like first line. I think counterintuitively we put no standard. We don't even discuss what our rule set is. We just wing it. What it's feels based.

[B]

Okay, you know, I'm not going to agree with that. I'm definitely going to do rule sets. I'm going to go with rule set one. Okay, let's go ahead.

[A]

But the only issue is I don't know, there's so define. Tell me what rule set one is again.

[B]

I'm gonna pick the ones that I think are just all arounder best in real life. Like the ones that I would actually prescribe first. And unfortunately for me, I think that's gonna be pretty boring because we're going

[A]

to find my issue is first, I don't like because we have medications that are for treatment resistant depression, and we have medications that are great medications that you should never use first.

[B]

Well, I think we're going to get into that. But nonetheless, I think that you'll find it's going to be hard to see me violating my usual rules. And my usual rules are that I'll never pick medications that will cause weight gain or appetite increase if I can help it. And I try to minimize side effects. That's kind of rule one. And then rule two is most efficacious. So that tends to be how I go. I feel like a lot of psychiatrists out there go in the opposite direction. I think a lot of people go for most efficacious first and then don't worry so much about the side effects. But, you know, everyone's a little different.

[A]

My only issue is, like, mirtazapine. I'm going to. That's going to be a high tier on my list. And that causes a lot of weight gain. So it's like the patient population matters.

[B]

It does, but that's what I mean. All arounders. I don't use much mirtazapine despite its great efficacy.

[A]

All right, well, I'm going to use your list as what goes on the screen, and then I'll just yell at you when I disagree.

[B]

Okay, that sounds fine. All right, so what diagnostic class are we starting with in terms of picking medications?

[A]

We're doing depression. So major depressive disorder.

[B]

Okay, do we mean true recurrent biological type major depressive disorder, the cousin to bipolar disorder, or do we mean dime stored depression from personality and stressors that happens to meet major depressive episode criteria?

[A]

All the above.

[B]

I want all of the above. Oh, boy.

[A]

Okay. Yeah, understandably, you want a very specific set of rules of what we're doing, and I want nothing. We just grade the medications.

[B]

Well, obviously it's going to be Adderall because that's going to get you the most return visits. No, that. That's a joke. Do not put Adderall. Let's put Adderall into F or. No, not even question mark. Adderall immediately goes into F tier. Why are we going to do that first? Because too many psychiatrists will essentially ignore anxiety and depressive disorders and call it neurodevelopmental. Maybe not so many psychiatrists, though. I definitely see psychiatrists doing it, but just a lot of clinicians out there. I think for run of the mill meets criteria, major depressive episode, you gotta go with search, reline. Search, reline. Hold on, hold on, hold on.

[A]

Shouldn't we explain why Adderall's in the F class first to me, it's not obvious. It's not obvious.

[B]

That's not enough. Okay, go ahead.

[A]

There's, I mean, I think there's a lot of people will report that they feel better on Adderall. And we also know that methylphenidate is commonly used for geriatric depression. So we can't write off stimulants just with one sweeping blow. But maybe we can come back to it.

[B]

But I will explain more. Those are some good points. First of all, it's not a very good antidepressant. What you feel on a stim on method or cocaine or speed, which is what Adderall is, is a intoxicant effect, that is the euphoria and energy burst and you will build tolerance to that. Proper psychiatric treatment of a major depressive disorder is not something that you build tolerance to. Now there is something called tachyphylaxis on the order of years of exposure to a medication where a medication becomes apparently less effective. But it's not a long term solution. Freud tried to use it cocaine to treat a bunch of stuff. You can read his cocaine papers and everyone concluded it didn't work. It's like every few years people try to treat everything under the sun in psychiatry with a stimulant because it feels great and people love it. It's not a solution, it's a drug. Now for the geriatric class there is an exception that should be made for geriatric depression or geriatric neuro cognitive disorders that come with apathy. Okay, apathy, this is sort of a unique thing, not exactly negative symptoms, but apathy can happen in older age people and a little stimulant treatment can be helpful for that. But that's very niche use and not run of the mill major depressive disorder.

[A]

Yeah, I'm glad you brought this stuff up because what I do see is I see a lot of. Now you see all the time patients are treated for ADHD to the exclusion of all the other diagnoses. And the thing is, as you mentioned, people feel good on the medication. So oftentimes they'll say like, oh, it actually really helps my depression because the first few times you take it, boom, you feel great. It's a very rewarding drug. The important thing is it doesn't treat depression in the long term. And what I've seen with so many patients who have ADHD plus depression is you're, you're not treating the depression and you'll see irritability creep up. You'll see somatic symptoms creep up, you'll see all these other things. And then the ADHD isn't getting treated because you're the person isn't addressing the underlying depression. So, yes, it does work, in my opinion. It does quote, unquote, work the day, the first day, but it does, it is, it is a very ineffective antidepressant.

[B]

That's right. And if you've ever even just been treating what seems to be plain ADHD executive dysfunction, and there's a sense that the stimulant stops working in some sense or needs a higher dose after initially working for a few weeks. That's not the medication treatment effect, that's the drug effect. So do not fall for that trap. Okay, folks, it's important one.

[A]

So does that mean. Can we. Should we put methylphenidate as D or F?

[B]

F. Because we're talking about depression.

[A]

Okay.

[B]

Is it frozen? It looks. Oh, there we go.

[A]

Yeah, we're good.

[B]

Snapping into place. I think we should stop, you know, running our ideology and talk about actual depression of treatment of depression, though. And again, gotta go with my boy. Search relay. Oh, all right. Zoloft, boom, boom, squirt rolling as they like to call it due to the diarrhea. Um, it is a great medication. First of all. You can titrate it on multiple steps. Okay. Eight steps to the FDA maximum. Pretty useful. Secondly, just works. Works pretty great. Third, does not have much in the way of med med interactions. Arguably at a higher dose, may inhibit 2d6 according to some people, or maybe in older adults. But basically, clinically, not a problem. No significant QTC prolongation. Yes, does have more GI side effects, maybe, but those tend to dissipate at each dose after, you know, up to a week or so. Effective, well tolerated, great first line medication. Absolutely S tier I.

[A]

100% agree. It is almost always the medication I reach for first. I feel like I used to reach for Lexapro more like it was almost a 50, 50 split. And for some reason, I mean, maybe there is a reason. I actually tended early on to reach for Lexapro for boys more and Zoloft for girls more. I wonder if it had something to do with the fact that we're supposed to use the name Sertraline. I wonder if Sertraline has the most, I think the best safety in pregnancy and breastfeeding. And I wonder if somehow that just seeped into my brain. That wasn't something I was doing intentionally. I think it was one of those. When I look back, it's like Oh, I tend to reach for Escitaloprim where more often for men. Now I tend to reach for Sertraline first line pretty much for all patients. Now why do I reach for Sertraline in front of Escitalopram? So the main thing is you do see more because of the way these drugs are metabolized. Sertraline has a bunch of different sips that metabolize it. For patients that have a ultra slow or ultra fast metabolization of whatever escital pram's metabolized by, you will get patients who have really bad response to escitalopram more often than with Sertraline.

[B]

Yeah, I would say in my experience you do see a little bit more poor tolerance. Alexa. Just a hair. Lexapro used to be in my S tier. I used to reach for it first, but that was earlier in the career and across increasing clinical experience. Again, still a great medication, probably my number two. But I wouldn't put an S tier. I would put it into A tier. And you know, it only has four titration steps, unfortunately, which I don't like. I like to have more steps. I think that works psychologically and physiologically. For more people who are treatment naive, you've got to consider the possibility of qtc prolongation above 20mg because it hasn't been tested. Though it probably is unlikely. The FDA label kind of handcuffs you in the elderly population saying you can't go above 10 milligrams because you're being ultra careful about QTC prolongation. But similar to Sertraline, efficacious, relatively well tolerated compared to some of the other ones and few med med interactions. So pretty good med.

[A]

Yeah, I used to. In terms of. I guess we'll try to do a little bit of didactics in here. Acetelloprema is the quote unquote, purest ssri. I used to think that meant that it's gonna have the least side effects or just like the most direct effect. I find that sertraline has less side effects overall and sertraline is a little bit better tolerated, even though it is the quote unquote, most pure ssri. I've had patients who tolerate citalopram better than escitalopram, which goes against what we're taught. You mentioned the doses on sertraline. My one complaint is there's no 150 milligram pill.

[B]

There's a capsule, actually.

[A]

Really? I must not be able to get a coverage.

[B]

I don't know if it's available everywhere. Actually.

[A]

So many patients that I have to have on two pills, which is more inconvenient than. Yeah, I feel like.

[B]

But you get the option. You get the option. And then what I like about doing the step from 100 to 150 is that you can say, listen, if this doesn't work out for you, take the one hundred and half of the fifty, giving the patients real control. And then also, of course, if you have real control, then you have the sense of control I think can help a little bit of anxiety when it comes to med titration.

[A]

Yeah. But, yeah, we are in agreement. I have escitalopram at A tier. I would have been fine if you put it in S tier. I would not have fought you.

[B]

Now, speaking of what you mentioned in terms of pure purity versus dirty, I think I agree. Purity. Purity is very overrated, both in real life and in medications. And I would say that I love a dirty drug. Okay. I love medications that can do multiple things at once. You get it all in one pill. Now, this is a problem when the dirtiness. That means hitting multiple different types of receptors and having activity at multiple different types of receptors. It's a problem if that comes with weight gain and appetite increase, because nobody likes that. And it's bad for you physically. But for the rest of them who don't necessarily do that and have a little bit more multiple action. Good meds. I like those.

[A]

Yeah. And theoretically we should be using. Because I've seen people use the word dirty because it causes a lot of side effects. Dirty should mean it hits a bunch of different other receptors. I almost feel like slutty is a better word, but yeah.

[B]

Well, I mean, I thought there was going to be a implication of that without stating it outright. Dr. Malsberg. We don't have to get all zoomer about that. Speaking at YouTube.

[A]

All right, our next one is going to be Fluoxetine Proac.

[B]

What? I thought I was making this. You're. You're saying I apologize.

[A]

No, I'm not putting it anywhere. I'm just holding it.

[B]

That's okay. I. I want to do a bit here. So if you can put the Prozac down for a second. I actually would have done that with you if I wasn't about to do a bit.

[A]

All right.

[B]

But for major depressive disorder, I'm going to do a bit here. And this is controversial. I want to put lithium in S class.

[A]

Okay.

[B]

Put it up there. But there's a caveat.

[A]

Oh, great bit, Dr. Fu.

[B]

It's because lithium is all the way at the bottom there under the Xanax, as it always is in real life.

[A]

Wait.

[B]

Oh, yeah, there you go.

[A]

Boom.

[B]

Why? Well, if we narrowly define major depressive disorder as simply the state of depression that somebody is in, and then we take the population of people who have recurrent major depressive episodes that require medication, treatments and don't respond to psychotherapy treatments or lifestyle changes, as we go down and narrow the population of people that have experienced that, over time you are going to see more and more of those people who may have a bipolar depression, that the underlying cause is a bipolar disorder, not a unipolar depression. And on top of that, we have to remember that there are varieties of major depression. Again, not from personality, not from trauma, not from stress, but any more. Biological major depressive episodes can be agitated depressions where you have severe insomnia, you have just psychomotor agitation. Are these bipolar disorders? No, not by our modern definitions. But do they respond to mood stabilization? They may. And it can explain why the antipsychotic augmentation is so effective in the studies. In my opinion, that may be an artifact of our poor differentiation of people who have a physiology, let's call it a psychophysiology closer to a bipolar disorder, yet never actually qualify for a bipolar disorder. And yes, there are a couple little studies showing efficacy of lithium as an augmentation agent in unipolar depression. So I'm putting it up there more as a position statement than a true. This is a first line medication for

[A]

depression and I wanted to do position statements. That's why I wanted to make it feels based. I am supporting your S class of lithium and again, not for first line, but we talked about this. Nasir Gaymi is a huge proponent. He's, he is a proponent of the manic depressive illness being any sort of recurrent mood disorder independent of polarity, and feels that lithium is first line for any patients who fit that. And he's a big proponent of arguing that lithium should be used significantly earlier. And he thinks it should be used for any patients with temperament issues. One thing that's important that people need to, I think providers should get better at is using low dose lithium. So There's a good YouTube channel called Psych Education. It's Dr. Jim Phelps. He has a few videos that kind of walk through thinking through using low dose lithium. Now the thing is like it's just convent. It's not just convention. But with low dose lithium we don't need to be monitoring all labs or we don't need to have the same lab monitoring schedule that we have with higher dose lithium. We wouldn't expect the, the same level of kidney dysfunction, the same level of all the other problems with lithium. And I do agree that so many providers are scared of lithium. We should do it. We need to do a lithium episode. I've had so many people that say they're scared to use it and I feel like if we just did one good episode on using it, I think we would change two people's practicing habits.

[B]

I hope so. But as you know, I'm always like, oh, you know, can we really make an episode out of that? Just like today when you mentioned this as a topic, I was like, this isn't going to make an episode. We have to cover every single diagnostic class ever. But now it's obvious to me that you're right. So we'll keep that in mind.

[A]

All right, let's, let's. So you did your bit. I don't know if I would call it a bit. I didn't.

[B]

I don't know, I would call it a bit. But yeah, Prozac. Totally, man. I absolutely agree. That's the next one that we're going to put up. For me, that's a class.

[A]

So I'll let you go and then I'll explain why I have it in B class.

[B]

Oh, B class for you, man.

[A]

Okay.

[B]

Proax. Awesome. Okay. Is it the best tolerated? No, but it's kind of like Haldol. All right. It's so old that the FDM max is really high, so you have a really high upper cap in terms of level of drug activity when you need it. Secondly, that also means that the starter dose, the low doses, even 10 milligrams, can be completely efficacious for people who are medication naive or have relatively lower disease burden. Okay, great med. Another good thing about Prozac, just like Abilify, if your patient tends to miss doses, skip doses. Great medication. You can just give a higher dose and they skip a few doses a week. Long half life still gives you effective serum level. I believe they even had FDA approved a once a week version of Prozac at one point. Fluoxetine, that is called something else where you only have to take, I think it was like 80 milligrams once a week or something, which would be equivalent to a, you know, 20 milligram daily dose or something like that. I don't recommend you do this, by the way. These are strategies that you can use for patients with limited adherence, despite counseling downsides why it's not S tier? Well, maybe a little bit more sexual side effects, possibly maybe a little bit more activating or agitating in some and plenty of medication. Medication side effects medmed not side effects. Medmed interactions a little bit more common with Prozac.

[A]

Yeah, I guess. In terms of a few comments, the reason why I put it in B class is strictly has nothing to do with the medication itself. For some reason with Sertraline and Escitalopram I know exactly how to think about the dosing in terms of when I'm at halfway FDA max when I'm thinking starting dose. For some reason Fluoxetine always gets me a little bit nervous and I don't know if it's because there's capsules and tablets and I don't know. For some reason I get anxious about using Fluoxetine just because I think I've used it slightly less than Sertraline and Escitaloprim. Now I guess a few other comments.

[B]

I think you're right to feel that way. Go on.

[A]

Yeah. And I don't know if it's just in my head

[B]

but I would say that that's actually from the fact that it's the oldest one and therefore like Haldol, the FDA max is higher. Fluoxetine, I think it is easier to go too high to where you tip the scales for risk over benefit where there's more side effects than benefit and people just think that FDA maximums are equivalent. They are not equivalent. Do not assume that the max of FDA approval on one medication is equivalent to another. Fluoxetine is basically the Haldol of SSRIs.

[A]

Now the other comments with regards to what you're saying, I do think of it having population based slightly less efficacy compared to Sertraline or Escitaloprim. Maybe it's the Cipriani study, it just comes up a little bit less effective than Escitalopram and sertraline. There are more drug drug interactions. So any sort of patient that I'm worried about drug drug interactions I'm going to be a little bit more wary about. I do really like the extended half life. It is great for patients that you expect to miss a few doses. Now a lot of people categorize Fluoxetine as the most weight neutral. I think there was some study that like in a short, very short term there might have been like some even weight loss. I don't see a significant difference. I don't think it's anything that will make Me actually think that there will be a big difference if I switch someone from one of the medications to fluoxetine. Clinically, I haven't seen a big difference. I'm trying to think if there's any other comments that I have with regards to Fluoxetine, it is known to be a little bit more activating. I don't typically see it much worse though than, than Escitaloprim. Yeah, that's, that's my, my reflection.

[B]

Yeah. You know, when it comes to weight gain, I personally try to disregard the hard numbers found in population studies because the population studies can't differentiate between weight gain as a direct metabolic cause of a medication and weight gain as a consequence of treatment. What do I mean by this? If you sedate a person or if you treat their anxious depression, that lowers their appetite, then their appetite will come back. And if that person does not already have healthy eating habits and they happen to be in the United States like our patients, then they're probably going to gain weight. Right. That is different than a medication that we know to directly stimulate the appetite through some known mechanism or that even induces a drug created metabolic syndrome, like for example, Seroquel. Right. So I, I, I don't consider any of the SSRIs except for Paxil a direct weight gain causing medication. Can they apparently cause a more drug driven weight gain in some patients? Yeah, yeah, you see that occasionally, but you can kind of tell from actually checking in with the patient about their eating habits at baseline and their eating habits after the medication. Now if we were being just straightforward about this, I think the next one that we would rank would probably be Paxil. But before that I want to add more into the F tier.

[A]

Okay.

[B]

I want to add, we have Dexedrine down there for some reason. Let's just put that right next to the Adderall. And I'm also going to go ahead and put in any benzos. So Adivan, Xanax, both of those go into F tier as well. Where else do we, what else is on the list here?

[A]

Okay.

[B]

That's all the ones that we have there.

[A]

We might as well put, I don't see dextron. Ah, there we are. Right there.

[B]

Right there. Okay. Okay. We'll hold off on the rest for now. I think we put all the benzos there.

[A]

Right. Why are you putting the benzos in F tier?

[B]

Again, similar to the stimulants, they are symptomatic treatments that create habits, build tolerance and stop working. They're not fundamental treatments of the Underlying condition so much as they are that they're drugs that help people feel better temporarily. You know, really not too different than a prescribed version of a street drug in my mind. Okay. Controversial. I know, I know back in the day, especially for the word, well, population. A lot of people would give a couple weeks of benzos with the first start of the ssri. Okay. I think if you need to do that, you may be using SSRIs too early. Okay. If a patient is going to react with that level of anxiety to an SSRI and they are not so psychomotor, you know, slowed and majorly depressed, why aren't we just giving them a talk therapy and behavioral activation instead? The effect size is the same. While why subject them to the ssri? There's really no point to do that, right? No need for the medication unless the patient is motivated, willing, feels good about it, or it's like a medical necessity. And anyway, I do prefer to stabilize the sleep using other agents anyway.

[A]

So I agree with putting in the F class. I will again defend it a little bit. There are a lot of patients that I'm not. Acute stress reaction is not what I'm trying to tell you. When patients have very high stress and I see an agitated type depression, I've seen it be incredibly helpful. Especially patients that have really, really, really bad insomnia. I'm not talking about chronic insomnia. I'm talking about patients who. I'm thinking of a lot of patients who have like a ton of stress at work, have some, some major crisis or death in the family. And the benzodiazepines can help as a short term, one week prescription to get over that crisis, which is partially depression. Now I agree. I don't think of it as. It is symptomatic treatment. You can use other sleepers. I do find the benzodiazepines are the most likely to have not a lot of problems when not in terms of long term. I'm talking about trazodone. Sometimes I'll have patients who have a paradoxical reaction with the metabolite. Um, other medications, sometimes they don't work as well or they work for a little bit. The benzos will knock people out. So I do keep it in F tier, but I don't think it's a completely useless medication even in short term depression. Although I'm not thinking of it as treating the depression so much as much as things going along with the depression. In sense, it's keeping them functional while under a lot of stress.

[B]

Yeah, it's not ineffective, it's that it's not effective for what we're trying to do. That, that's my philosophy. Yeah. I think that what you're referring to can just as easily be accomplished by high dose hydroxyzine, low dose trazodone, gabapentin at higher doses, you know, mirtazapine if you have to Seroquel over benzodiazepine any day, there's a lot of choices. I think if we're going to do a short term hypnotic, I would reach for a cerebral every time over a benzodiazepine. Don't get into it is what I say we're doing. We're doing a tier list absent of. What's that?

[A]

I said we're doing it. We're going to do a tier list for insomnia. So we, we'll, we'll get into the more details in that one.

[B]

Yeah, yeah, yeah. It's not as if benzos are without adverse effects. It's just that so often people love the drug effects so much. Understandably. They work great, you feel great, we ignore the adverse effects. But people are just as likely to have adverse effects on these medications. I just stay away from them.

[A]

All right, let's move on to our next one.

[B]

I think we got the Axel Paxil. Oh boy. You know, it's a very hard one for me to place. It's gotta be either B or C and I have to fight against my bias. I think it is a B class medication. Ultimately with a big caveat, I would give it B minus if I can because it's quite effective. Okay. There's a reason why it's been FDA approved specifically for so many neurotic conditions. It's great in terms of its efficacy, it works quickly and it's a sleeper on top of being an antidepressant class medication. Get a lot of bang for your buck there. All in one tablet, easy to dose. There's a long acting form and a short acting form. A lot of good options. But weight gain, weight gain, weight gain, anticholinergic effects, dry mouth, dry eyes, constipation, what else? With Paxil that's a problem. Well, it's a very short half life so if somebody is not very meta adherent then it's likely to cause a little sense of withdrawal in some people. So it's uncomfortable. I was taught that hey, this is something you should consider for patients of poor method adherence. They'll notice to withdraw and remember to take medication. I feel like that's very outdated Set an alarm on the phone, use a pill organizer. I think that's a ridiculous notion. So despite its efficacy, I cannot rank this one highly. I certainly never use it first line and I hardly ever prescribe it as you know, because of the weight gain.

[A]

First off, that's hysterical. The idea of using it for patients who are not medadherent because it's so punishing when you miss it.

[B]

Yeah, it's ridiculous.

[A]

Just a small plug to leave a review if you can Leave a review will help other clinicians find our show and will let us keep making it. If you're on Apple podcasts, open the show page, scroll to ratings and review. If you like us, tap five stars. If you're not sure what to put for the review, just say hi Dr. Fu. And if you're on Reddit or YouTube, leave a comment. Dr. Fu reads absolutely every single one. Let's get back to the show. I just got a dog. So there's the new movement is all positive reinforcement and that is not using positive reinforcement in your line of reasoning for medications. So paroxetine because we got to make sure we use.

[B]

Don't tell me they're gentle parenting dogs now too.

[A]

There's a lot of people who refuse to use any sort of balance training. But paroxetine, they're called SSRIs selective serotonin reuptake inhibitors. They are not all selective. So paroxetine hits inhibitors is anti muscarinic and that helps me to organize all the information that you kind of just mentioned. So it is sedating. It does have bad withdrawal because we know any anti muscarinic medication is going to have bad withdrawal, short half life now bad for pregnancy. And what's the other bad one? Bad for weight gain. Most of that you can categorize as anti Muscarinic. I'm not saying that that is the reason why, but that does help me categorize a lot of the problems with Paxil. Now as you mentioned, the anti muscarinic also probably has some effects with regards to helpfulness in some anxiety disorders. And that's why you said neurotic conditions but anxiety, you know, for, for people who don't. Don't know what that means. The it has a lot of.

[B]

I think that's why it got an approval for ptsd. Right. Because the PTSD treatment for diagnosable PTSD early on majority of what you're really, what you really should be doing is sleep stabilization. Yeah. And Paxil will both your sleep stabilization and the treatment of the severity of core PTSD symptoms. So great med for that, but I'd rather skip the weight gain and just give a sleeper with Zoloft, which is what I usually do.

[A]

Yeah, I would probably put it in C now. It's funny, I think we're balancing, like right now. A lot of people just simply don't use Paxil, so I think it's higher rate than that. But then anyone who's using Paxil, first line, you gotta knock it down. I probably would put C, but I'm fine with B.

[B]

You know what, let's put it in C. You've convinced me. Okay. It was on the edge. Put it in C. You know, bad Paxil, don't give so much weight gain. We can use other things.

[A]

All right, what's our. I think, round out the SSRIs, but I'll let you keep us going.

[B]

Should we? Well, let's briefly put Celexa in. It's basically Lexrophobia that makes you more sleepy and it causes you more QTC prolongation. I never use it because of that, because there's just so many other choices. But I can see why an older psychiatrist might use it. It has to be in B class. It's again, just Lexapro, but it makes you more sleepy and it prolongs your heart rhythm. So it's not a bad medication by any means. It's just got some downsides. And in my opinion, there's hardly a reason not to use a different medication.

[A]

All right, let me go off my soapbox in this one. So little Didactics. Citalopram is both enantiomers of Escitalopram, so that's why it's named Escitalopram, because it's the S enantiomer. So theoretically, the R enantiomer has a little bit of antihistaminergic activity, and that's why it's probably a little bit more sedating. Now, I have seen on their Reddits, people being like, oh, a nurse practitioner. Now I hate. I strongly dislike the NP hate on Reddit. And I try my best to defend the NPs. The they'll say, like, the nurse practitioner switched them from Escitalopram to Citalopram. What a moron. And what I'll say to that is oftentimes these medications like the reactions patients have to medications isn't what we would expect based on what we know pharmacologically. So I don't see patients respond to Citalopram as if it's escitalopram. With a little bit of sedation, I've seen patients get opposite responses and opposite side effects. I've seen patients who have not been able to tolerate escitalopram and then tolerate citalopram perfectly fine. So now I don't think it makes sense to go from escitalopram to citalopram for, for most of the time. But if someone does have a good response to citalopram, I don't say like that's not possible because they something. You know, we don't know how these medications work exactly. And how patients respond to them is. Cannot be deduced from what we understand pharmacologically. So that's my soapbox.

[B]

Yeah, it can be defended exactly as you have. I simply never do it because there's just too many options out there. You know, if you take every permutation of hypnotic anxiolytic sleep support medication, plus primary serotonin based anxiety depression medication, never have to reach for the same medication twice. You know, if it's been a few years and I want to do a trial again and they're super against escitalopram and there's some reason why I want to use it, I really can't imagine the situation, I might do it. But basically, if I'm on my third or fourth medication and this isn't some kind of a super zebra patient like someone with autism spectrum disorder, borderline personality disorder, psychotic features, and like three hospitalizations where it's like clearly both a social, psychological and a biological thing and I'm doing all kinds of weird stuff. If you're treating major depression and you're on your third medication in a row with no remission, reconsider your diagnosis.

[A]

Yeah, absolutely. One last comment about citalopram. I feel like 40mg is the max dose. Except it's 20mg is the max dose for I think elderly patients, I think patients over 60 patients who are poor. Two C19 metabolizers. Yeah. Max dose is 20 milligrams. There might be another population, but I can't think of it off the top of my head.

[B]

We have not yet exhausted the rest of the ssri. So let's do Luvox. The sigma. The sigma of the SSRIs technically has sigma receptor activity where.

[A]

Sigma grind set.

[B]

Luvox. Yeah, Sigma grind set. Antidepressant. I don't hear.

[A]

I'll never use it for.

[B]

I think we should keep it in question mark. It's just simply such a backline choice that you pretty much only use in patients of OCD that I don't think we can fairly grade it. The Sigma did some mysterious ssri. That goes its own way, isn't it? I've had some patients get a little sedated on it. It's not too hard to titrate. The main reason why I don't use it more is because I think there's random insurance denials and it's just again, too many med Med interactions. There's no particularly good reason to use it over the other. I haven't seen that Sigma thing actually play out in better clinical response for major depression. So very niche pick, you know, but maybe it's a sleeper hit that we're just not using enough. Hard for me to say.

[A]

Yeah, the med bed interactions, it inhibits, especially CYP1, A2 and then basically all of them. 2C9, 2C19, SIP3A4. I think it was studied a little bit for like Covid because of the Sigma enigma.

[B]

Yeah, apparently there was a signal that it reduced Covid mortality, I think. But who knows? Who knows?

[A]

All right, what do we got next?

[B]

Well, we surely are now in the realm of the Snris Boom. And I think we should start with good old Effexor Ventures. Okay. Geez. Between B and A class for me. Between B and A class. Let's put in B. This is a B class.

[A]

B for me.

[B]

Benlafaxine. And why? Well, you know, it works. I have to admit, it works. And you know you're gonna see all kinds of psychopharmacologists crying, you guys are pretending this is a snri. There's no norepinephrine activity until at least 150. Some studies do not show a blood pressure response when used with so and so medication. In the studies, there's no norepinephrine activity. Well, there may not be, but belief is strong. And I just tend to see more response on this compared to some other medications. For some reason I can't explain. It seems to be pretty well tolerated actually. The only downside is the awful withdrawal syndrome. I'd probably put it in a class and I'd probably use it a lot more often. I might even put it in S class if it weren't for that terrible withdrawal syndrome. Famously the worst withdrawal syndrome out of all the antidepressants. I've even seen an elderly person get medically hospitalized once because of the withdrawal from Venlafaxine. So, you know, works well, but just be careful.

[A]

You.

[B]

You want to, you know, taper it slowly. It's also a little annoying, I feel like, because I want. I'm fine with it titrating up, but I also feel like I wish it came in smaller increments for titrating down. But if you have to come off of it, you're just gonna have to accept some brain zaps and whatnot.

[A]

Yeah, I. I think I have less warm feelings for Venla vaccine. Yeah. The withdrawal is famous. You'll hear lots of horror stories. That said, I've actually had relative success. The patients that I've tapered off, I had no major hiccups, but I'm not minimizing it. I've also seen horror cases. I've seen patients in the emergency room crying, just feeling absolutely horrendous as a result of them affecting withdrawal. So I'm not.

[B]

I'm not saying very hit and miss.

[A]

I'm not saying. I'm not minimizing and saying it's not real. But for the average patient, before they have a complicated withdrawal, I don't kick and scream. I tell them to probably be careful about what they read online. Now, I don't like Venlafaxine because it's improvement over SSRIs. It's relatively small, so it's not like it's this big hit medication. It can raise blood pressure, it can raise heart rate. So there are more side effects. There's more problems. Now in Europe, there's a warning for overdose concerns because of its cardiac effects in overdose. I think that's something in the US that we don't pay as much attention to, that there are cardiac problems as a result in terms of arrhythmia risk with these medications.

[B]

Yeah.

[A]

So I tend to avoid it with anyone with anything.

[B]

It's just not as much as the TCAs. I mean, it's real, but it's just not as much as the TCAs. That's all.

[A]

Yeah. So I think of it as, like, very marginal improvement over the SSRIs. A lot of side effects, a lot of problems. Now, I don't think it's a useless medication. I will use it, but I don't think you jump the gun. I don't think there's ever a patient that I'll use it first line, unless I'm using the two birds, one stone, like migraine or something very specific that makes me feel like it would work. But in general, I'm doing First line sertraline. SSRIs. I don't typically start with emfaxine.

[B]

Yeah, I don't go for the SNRIs unless, as you say, they have migraine disorder, a diagnosed fibromyalgia. I don't believe in it, by the way, for apparent adhd. If you really think there's a diagnosable adhd, you should probably be using at least Atane Strattera. But, you know, it's useful. I'm warm to it because I've been burned enough from receiving for some reason. I don't know why this is. Maybe you can shed some light on this in the community here. For some reason there's a lot of people doing Venlafaxine plus Zoloft. And no, it's not a cross taper.

[A]

Okay.

[B]

They love to do Venlafaxine plus Zoloft, Snri plus ssri. I totally disagree with it. But then I've been burned by trying to pull off the Effexor first and seeing worsening and then putting them onto Effexor monotherapy and maxing it out and seeing significant improvement. So I've warmed to it a little bit.

[A]

The combo that is a little famous is the California rocket fuel, as coined by Steven Stahl, which is Mirtazapine and Venlafaxine. Anyone who's using an SSRI and Snri. Stop it. Stop it.

[B]

Yeah, pick one, please. Pick one.

[A]

That's, that's bad.

[B]

You know, we might as well throw a symbol on here. I think it's C class. You know, there's nothing terribly wrong with Cymbalta. It's on the first one. It's just the first one there. It's again. C class. C class.

[A]

Ah, I, I, I don't have, I have Ven.

[B]

Oh, you want to put it up in B class.

[A]

I think of it as. I think Venlafaxine is probably a little bit more effective. And then duloxetine has probably little special indications with regards to pain.

[B]

Well, again, the Duloxetine runs into the same problem as the Venlafaxine. It's unclear how much of a norepinephrine reuptake inhibitor actually is. It's more bad marketed that way. Yes, we believe it.

[A]

What's that? It's more balanced than benlifaxine, supposedly.

[B]

But I believe when they actually go in and study the norepinephrine reuptake inhibition using that method where they measure the blood pressure after giving. I already forgot the name of the other chemical, but it may not be very potent at all. As far as that goes, the only true Snri on the market may be

[A]

Lebonacipran. Wow.

[B]

I can't remember the brand name right now, but it's Milnazepran. Savella. Savella. I'm going to go off of my very limited experience with Savella, which I've been able to get approved for patients who have existing diagnosis of fibromyalgia who I'm treating for depression because I obviously can't use Fatzema. My patients are low income, so no one gets Fedzema. I would put this one maybe an A class.

[A]

Whoa.

[B]

Maybe, maybe, maybe. Yeah. Actually fulfilling the promise of the snri, you know, and yeah, lots of good titration steps that you can use. Do we also have does venalfaxine lying around here? Yes, we do. Pristique. This is again theoretical. And so I'm going to let you move these around if you've got more experience with them than me. I can't use it very much. Again, too expensive. But I'd put it up in a class. Better tolerated, less withdrawal. I've heard than the ven for some reason, but who knows?

[A]

Yeah, we've already talked.

[B]

I'm shooting in the dark here.

[A]

Just some, some facts. So it is not, it isn't generic. Whether it's on formulary is a different question. Desvenlafaxine theoretically is. Has less drug. Drug interactions than Benlafaxine. I haven't noticed significant difference in terms of efficacy with the two medications. I would put it at probably.

[B]

Yeah, it's like hit and miss level for the SNRIs. I feel like it's a. Some people it's like no better. And then for some people, suddenly it works. It's very hard to say. Could be completely random. And based on the. What's happening in their lives, I can't rule that out. But you know, when you're doing med management, you just kind of have to work along a certain set of things.

[A]

All right, what do we got next?

[B]

You know, we probably should have done the atypicals. Oh, yeah, Klonpin goes up there. We probably should have done the atypicals before did the snris. Because personally I would consider atypicals before the snris. I don't mean atypical antipsychotics. I mean the, you know, non traditional antidepressants, Wellbutrin and Remeron. Okay. Despite my hatred of weight gain, I must put Remeron in A class. Okay. If it was not for the weight gain. And in many patients, especially Asian patients who are more sensitive to antihistamine effects, significant sedation. Oh, man, it works so good. Works so good. It's almost S class. Great med. Mirtazapine. Let's put that at the front of the list.

[A]

Yeah, I have it.

[B]

I have it on right after Lexapro.

[A]

I have it in probably the S class now, in my opinion. Oh, oh. For some reason. There we go. In my opinion. First line medications for antidepressants. I'm thinking of escitalopram, sertraline, mirtazapine, bupropion. I think those are all reasonable first choices depending on patient profile. I very, very, very rarely deviate from those four. Now, mirtazapine, weight gain. So for patients that need to gain weight, great medications. It is incredibly sedating. Incredibly, incredibly, incredibly sedating. Warn your patients that they will feel like a zombie. Now, why do I think it's important to warn patients? Because I tell them, the first three or four days, you're going to feel like a zombie. Usually what I see with patients is it gets better. And as they adapt that zombie hollow, like, can't do anything feeling is better by day four. And usually it gets better every single day. And there's. Think of the first period as kind of getting past the hump. Another important thing, some people say at the higher doses it's not sedating or it's activating at the higher doses, the better way to put it, in my opinion, is it's not going from zero to seven and a half is not as sedating as going from 15 to 30. So to me, the important thing to teach is it's.

[B]

Did you mean the opposite? It's more sedating to go from zero to seven and a half than it is to go from 15 to 30.

[A]

Correct. Correct in that, like, it going from 15 to 30 is more sedating, but it's significantly less of a jump than going from 0 to 7.5. In fact, 0.

[B]

Yeah.

[A]

The most sedating jump is 0 to 2.5. So for patients who are on super low dose and they're on, you know, I'm on 7.5. What do you mean? I need to get to 30 milligrams. They'd be like, are you nuts? I'm going to be a zombie. You have to teach that. I don't say, oh, it's activating and you'll have more energy. But the jump isn't as big of a jump from the beginning stages.

[B]

Yeah, that's the old tradition, right? I don't believe in it. I don't think it stops being sedating or increasing sedation at any dose. As you say, it is less of a serious issue for most patients once you get into the 30 range. But I've had patients that just can tolerate that change anyway, so it really depends. And again, Asians more sensitive to antihistamine effects, so just be aware of that sedation. Great med, by the way. Forgot to mention, if you're afraid of GI side effects and sexual side effects. Okay. And actually gets you probably some norepinephrine action through a unique mechanism versus snris, which on paper are named to that but may not get you much. Norepinephrine action. Also has a pathetic but still statistically significant reduction in some populations for meth use disorder. You can get like three less meth days in the month. Pretty good, huh?

[A]

Yeah. The reason why you bring that up is there's like this paper of like, we now have a drug to treat meth as if like this is going to totally changed the landscape of meth use. Yeah, it helped a little bit.

[B]

Well, it doesn't stop everyone here from throwing it on every single person who was incarcerated that has a meth use disorder and wants to sleep because the dorm is noisy. A lot of that going around around here?

[A]

I imagine so, yeah. Great medication, very sedating, does increase weight, does help with GI side effects. So it's a poor man. Zofran.

[B]

Okay, Wellbutrin, Great med, Hit and miss tolerability. Love to throw this on on almost everyone who doesn't respond to just one medication. A class, certainly a class as well. Great medication can give you a pep in your step. Beware of using it in patients who have a lot of baseline anxiety. Even if this is a medication that seems to treat anxiety in the long term, if the patient can tolerate it, the initial burst or worsening anxiety may be intolerable. This is also a medication that you can use with or without depression if people are having problems reaching orgasm. There's been several studies showing that this helps you reach orgasm faster. So you can use this for anyone with an orgasmic disorder, little weight loss and appetite decrease, which a lot of people like. People use it off label for adhd. Never seen it work for that, but why not go ahead and throw it on? Watch out for the sleep problems and lots of nice little formats. You can play around with it. You want to only have them exposed to it in the daytime for some reason. Sure. Use the SR once a day, but do not play with the dosing. If you're using it as monotherapy. If you're using it as monotherapy, you should probably just use to XL types.

[A]

Absolutely. I think this is a spectacular medication. Doesn't have very sought out by patients because it doesn't have the typical problems that we see with there's not weight gain, there's not sexual problems, there's not sedation. We think of it as a mild stimulant. Now my warning to providers is a lot of times people use bupropion for anyone who says they don't want weight gain for any sort of disorder. To me as a clinician, you should be learning patients that respond well to SSRIs versus patients who will respond well to bupropion. There are patients with depression that I say, like I'm telling you, that Zoloft will be a much more effective medication for you. I think, as you mentioned, with anxiety, yes, it does help anxiety for some patients, but it does worsen anxiety for a lot of other patients. And you see, I feel like we see pendulums swing so far as if people are answering the question of either yes, it's bad for anxiety or no it's not bad for anxiety. And there's nuance here. So I feel like in med school I learned never use it for anyone with anxiety. And now I see all over LinkedIn of like, why are you not using it in your anxiety patients? What's wrong with you? For patients who have that very strong anxiety, I do see it worsen long term. And oftentimes what I'll see is they'll get a little benefit in the beginning as their depression gets treated. But then four months, six months down the line, I do see a little bit increase in irritability, a little bit less, little more insomnia. There are problems. So there are patients that come wanting a medication that doesn't have problems. And I provide the psychoed that like, yes, it would be ideal that we could have an SSRI that doesn't have problems. But that said, I don't think we use an incorrect medication for you just because it doesn't have the problems you don't want to have.

[B]

Yeah, yeah, the anxiety increase can be substantial. Don't just throw it around because the database shows that the people who tolerate it improve their anxiety. I have had patients with severe anxiety actually end up having a major catastrophe at work because of how bad the anxiety was when they started it for a medication like Wellbutrin in An anxious patient. If we are going to trial it, I recommend they try it for the first time on a weekend or something or when they have nothing to do.

[A]

Yeah, awesome. Let's see. Also it is a 2D6 inhibitor. Make sure you get your blood pressure

[B]

and heart rate 2D6 inhibitor and thus can be used to increase effective dose of your Abilify Maintena and Aristada which maxes out at a 15 to 20 milligram daily dose. This is not medical advice that may increase possibilities side effects and it's technically an off label strategy.

[A]

Yeah, and we also have ovelity, which I don't think I didn't. I used a template that already existed. This one doesn't have ovelity.

[B]

Yeah, this is a weird template. Where are my TCAs? Where are my Maois? And yeah, I had it on my template.

[A]

But I like this one because it had colors and it was already pre made and I couldn't update it.

[B]

Yeah. And why are there so many antipsychotics?

[A]

To make it fun.

[B]

It's weird. It's a weird template. Let's do trazodone. I think I have to put poor old trazodone into C class. C class because we're rating it for major depressive disorder. We're not rating it for trauma disorder or insomnia. It's just not tolerated enough by most people, you know, at a high dose, a dose that you would need for the antidepressant effect. And I don't think when I have had it at that high for people that it's that efficacious for depression. Primarily quite efficacious for sleep, not necessarily all that efficacious for depression. But that again is probably a bias because I only get it up that high in very rare individuals who happen to need this severe polypharmacy type treatment and also somehow don't have a QTC problem at a higher dose of trazodone.

[A]

Now I guess some teaching points. Low dose trazodone is not a small antidepressant. So it is one of those medications that you need to get it to the higher doses. The mechanism is through serotonin reuptake, the same as the SSRIs, except it's not selective. I haven't seen it be a home run. I typically, as you say will have low dose trazodone and then an ssri. I agree with the C class recommendation.

[B]

One thing to add, trazodone has an active metabolite called MCPP and that can cause Agitation in some people. So don't be surprised if even at low dose trazodone, or especially at low dose trazodone, some patients report a paradoxical effect on their sleep or, or their mood. Not everyone likes that. It's apparently a designer drug that people don't like and cause dysphoria.

[A]

Important teaching point here. So it's tough because what I do with that information is be careful about how you talk to patients because you're using it for insomnia, which has a lot to do with anxiety. And by telling them that they might have a paradoxical awful reaction and not sleep that night, you're going to worsen their anxiety using that medication. The flip side is if someone comes and says I slept terribly on my trazodone, you have to believe them. And it doesn't mean you don't provide psychoed, but just be wary about how you provide that. Psychoed.

[B]

Yeah, I pretty much say, hey, this works great for a lot of people and for some people it doesn't work at all and might even make the sleep worse. We don't know. Why don't you just try it out? See if you like it. If you like it, keep taking it. If you don't like it, don't keep taking it. That can be helpful. But I think your population is more neurotic than mine.

[A]

Believe all insomniacs. All right, okay.

[B]

We're low on time. Let's go a bit quickly. I'm not going to put any of the antipsychotics on this list except for Abilify. No, no, no, don't even put them on the list. I don't even want them on the list. Get them off, get them off. Terrible. They shouldn't be on this list. That's for a different day. But actually, I'm sorry, we're going to put Abilify, low dose Abilify in S tier. Oh man, that's controversial. S tier. Get it up there. But it has to be. That's why under, under 5 milligrams. The data and the clinical experience shows that this is a very good augmenting agent. Works great. Probably has a unique effect. That's probably true also then of Brexpiprazole and maybe of Raylar. Not clear. A little early to say, but you know, the dopamine partial agonists seem to be pretty good as an add on. But while we're briefly putting it in S tier, let's put it down a. Thank you.

[A]

Very good.

[B]

Read my mind.

[A]

I refuse to let you get away with putting an S tier. You are not going to.

[B]

Yeah, you read my mind. I wanted to emphasize how efficacious it is, but even at low doses, the risk of tardive dyskinesia is there. And especially in patients without schizophrenias. Okay. The risk of tardive dyskinesia is higher.

[A]

Now let's see if we can do so. One helpful thing, TDScreen AI is a cool, free AI to help screen your patients for dyskinesia.

[B]

I didn't know this exists. I don't know. Until I can read a research on this, you should know how to do an aim. See the research, read the aims, read the aims, read the, you know, directions and actually do an aims. And you can do a modified version of the AIMS over video. If you have assistance from a family member or a nurse.

[A]

I'm not letting you lead to an increase of antipsychotic use for.

[B]

I don't think you can get any higher. Do not dose Abilify above 5mg. If what you are trying to do is trying to treat major depressive disorder without psychotic features, do not do it. Just don't do it. It's not worth it.

[A]

So, yes, please, please be wary, be mindful when you use it. Don't throw it out. I think there's so many important caveats. Make sure you have the right diagnosis. Make sure you're not ignoring other things. Please don't use more antipsychotics unless you feel very confident with what you're dealing with. Okay.

[B]

You know, there's going to be a lot of laypeople who are going to skip to the end of this video. So let's put it down in the question mark section. Abilify.

[A]

We can't go from S tier to a tier to question mark.

[B]

Yeah, I think that's indicative of how we want to think about it.

[A]

Okay.

[B]

And in the same way, let's go ahead and put Seroquel in the question mark.

[A]

Well, I agree with. I think we should put it in.

[B]

Oh, no, no. Come on. Good old Seraph. It's just awakening.

[A]

It works so good. I was thinking. I, I didn't. I didn't have it in particular. I should be going like this.

[B]

I would not put it anywhere because it's an augmentation agent. So it goes into question mark. But as an augmentation agent, it's pretty dang good. I would give it a B. It works great. And anyone who doesn't care about weight gain and appetite increase, but it Definitely causes a ton of weight gain and appetite increase. Increase. It's got lower risk of tardive dyskinesia than other ones. And it's pretty dang well tolerated. It's so well tolerated, it's hard to get patients off of it sometimes once they're stabilized because they're like, oh man, this helped me so much. And then their sleep will destabilize when you pull it off, at least temporarily. So use with caution. Seroquel.

[A]

Yeah. And I hate. I don't want to have the high risk medications be up top. Have people be prescribing lithium and antipsychotics. Make sure you have the right diagnosis.

[B]

People.

[A]

Treatment resistant depression is where personality disorders go to hide. Let's carry on. Yeah.

[B]

Oh, lithium. Actually, I'm not as worried about if you're sticking to 300 to 400.

[A]

No, it's fine

[B]

dose.

[A]

Yeah.

[B]

Okay. Vorteoxetine. It's okay. It's all right. You know. You know that meme maybe on YouTube where if that guy eating that, I think it's like a burger or something. He's like, ah, that's all right. That's Trinitylex. So I think it belongs in B tier.

[A]

I think it's B. I've used more.

[B]

Really?

[A]

I'll let you go. Okay.

[B]

It didn't really pan out in terms of the promises. Right. Like helping with cognition or is this the one where they claimed there was some improvement in sexual side effects? I think there might be a little bit of that.

[A]

Whereas you have the signal for sexual side effects. 40 OxyTime has the maybe cognitive effects question mark.

[B]

Oh, yeah. When they wanted to call it Brintolex, but there's always like some kind of nsaid. Already called that. Anyway, I would put vortioxetine and vilazidone on the same tier B. This is expensive. It's not particularly more effective than others. If you're having someone who has a hard time tolerating medications, they might be able to tolerate it better than the other ones. It's worth a try. Is it something you reach for first? Absolutely not. Is it something that you avoid? No, it's called solid B tier.

[A]

Yeah. So I've used a little bit more of the velazidone. You know, I don't think I'm not gonna be using it. First line I have. It did help a little bit with the sexual side effects. So I had a bunch of guys that it helped a little bit. It wasn't foolproof. It wasn't like they had no sexual side effects, but it did help a little bit. So I do like it as a medication and I will. It is. I feel like some of these medications I'll just never get to Velazidone. I do get to.

[B]

Yeah. How about esketamine? Whoa. Everyone loves their ketamine today class medication for me. Yeah, this is a C or a D maybe. D. We're gonna upset the people put in D. It's in D. Why is it in D? It's in D for me and I won't budge from that. Why? Works great in a select amount of people, can be life saving in a select amount of people. But unfortunately probably has opened up the field to more peddling of drugs instead of treatment and also only a seven day treatment effect. And I don't think that a lot of these clinics giving out Spravato are doing the work that they should be in actually getting patients into therapy and lifestyle changes, which is how Spravato is going to work. It is a short term treatment that helps you lift out of the depression and then you have to do hardcore lifestyle changes and psychotherapy on top of that. It's not like one of the other medications in the S or the A tier where you can basically get someone mostly out of remission even if they do zero work and you know, have them live their life long term with minimal side effects. Spravato, a bit of a problematic medication. I'm glad it was discovered. I'm glad it's being used sometimes responsibly. But a lot of caveats.

[A]

I have lots of thoughts that I'm not going to go into here. I'm going to say something which I shouldn't say because it's not going to be heard correctly by the people who I want to hear it. But to me, an archetypal risk is, and I'm basing this off of the few things I've read, this is not a political. But this is nothing. Elon Musk to me is an archetypal hit story of the risks that I see with esketamine. And what I mean by that is that there's so many patients now who are seeking it out to use it in a sense to ignore other problems. And they're using it essentially as a drug, as in they're making lifestyle choices that are leading to. That are almost bound to lead to stress levels that are not manageable. And then they're trying to compensate with a drug to keep them going. And that's what I See, with a lot of patients who are seeking out, a lot of the controlled substances is. And that's not all patients. I've seen it. It's a spectacular treatment. I love that it's short, acting short. I love that it works right away. There's a lot of patients that it helps a ton of. But so many patients are now seeking it out instead of looking at the other problems in their lives. And I have a lot more to say that I'm not going to right now. But, yeah, I agree with the, the.

[B]

The cd. Um, I wish there was BUS here. And I know it's not an approved medication for depression, but I do think that the aziparones, because there's a new one too, which I don't see a point in using when we abuse brone. I hope you can edit this in, but I would put buspirone into the B class. Okay. Because it's just so low risk and relatively well tolerated. And it is pretty efficacious for anxiety, trauma and irritability, which often can come hand in hand in your major depression patients. It works for augmentation. Just don't under dose it. Start at 15, but be ready to go down if it's a patient who's more sensitive to it. And don't be afraid to take it to the max. Buspiron. Buspirone. Buspirone. Buspirone. Also, big fan of it these days.

[A]

I've also seen. Isn't there that small study that it helped with the sexual side effects of the SSRIs?

[B]

Yes. I also use it along with bupropion to help with sexual side effects. And yeah, it seems to have some efficacy for that. So if someone needs to stay on something and they're having too much energasmia, reach for the buspirone or the bupropion. Not a bad idea.

[A]

Lamictal.

[B]

I'm not going to put it up there. It's too niche. I would use it for people with obviously mixed depression or bipolar features. I would consider it for ocd. Do not put it up there. Stop it. Stop it. And then for some reason, they put lamictal. Xr. For some reason. Why do you do xr? I don't need it. Just use regular.

[A]

Where do you want to put it?

[B]

It's got enough risk that I don't want it being given more often. Unless you're a real pro, you know what you're doing and stop it.

[A]

Where do you want me to put it?

[B]

I will not sign off on this. If you leave it up there. It should stay at the bottom. It is not a mainstream treatment. Yeah,

[A]

there we go. Now it's interesting. I think there's, there's more to say about that. I think it does have some evidence for depression. I think of it as, now some people like to use it. I kind of was rallying against the bupropion because it's like people are saying, oh, someone doesn't want side effects. Then I use a medication that doesn't have side effects. But you don't use something that's not indicated just because the side effect profile matches the side effect profile that you want. For patients with emotional dysregulation and reporting depression, I do see it helpful. I don't see it helpful in MDD proper.

[B]

Yeah, it's. It's too hit and miss. The risk is too high and it's too easy for it to be basically a placebo because it doesn't really have so many side effects. I think it's an S tier med for bipolar, but we should not put it in the MDD columns. That's all I'm going to say about it. Where would you put your TCAs? I would put doxepin in C and I'll put amitryptyline and D

[A]

Sleep. Not for depression.

[B]

Oh, you use it for both.

[A]

Yeah.

[B]

And then probably clomipramine. It's like B and what's the other one I don't use? No one uses them. No point in doing a tier list.

[A]

I wish we did. I had the maois.

[B]

But consider them. Consider them if you have true treatment resistant depression, not just we're calling something that's trauma and personality depression. Please consider your TCAs and your MAOIs if you know what you're doing.

[A]

I would put the phenylzine and sledgeline patch in A or B tier probably.

[B]

Yeah, they're pretty good.

[A]

Yeah. Okay.

[B]

That's all the time I got. I hope people like this one. It's very clickbaity, very Internet, but hopefully it also has some useful information for people to at least make your own tier list, you know, because the tier list that you use for medication should really be tailored to your patient population. Patient populations are different and your diagnostic pool is going to be different and so your treatment response is going to be different too.

[A]

Awesome. Great ending point. I will see you next time, Dr. Fu.

[B]

All right, see you.

[A]

Thanks for listening. If you want to support the show, check out my very practical antidepressant course. If you want to check that out, go to Psycho if you prefer to read, you can go to Amazon.com you can just search my name Gregory G R E G O R Y Malzberg M A L Z B E R G and the book is Psychopharm's Guide to Treating Depression. It's a nice, easy, readable, practical guide to medications for depression

[B]

SA.