E9 - Depression - When All Else Doesn't Work

When the algorithm for treating depression begin to have more branch point than words hinting at what to do next, we'll come to your aid with this podcast. Tune in as we briefly review the treatments reserved for the refractive cases.

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Transcript

Dr. Amayo: 0:00

So we are assuming, you've done, you've done your due diligence, you've checked out. Are you guys having a social hour in here that I wasn't invited to? Because all I hear is him giggling from down the hallway. Welcome. So today we have a special guest Dr. Sweet baby cheese. I'm trying to do scholarly activity at the end of the hallway. We are too, three jokers are just laughing hysterically in the background.

Thanh: 0:27

Welcome to the Y in Psychiatry!

Dr. Amayo: 0:29

Hi, this is Dr. Amayo C/L fellow.

Thanh: 0:32

Where we delve into the intricate nuances of psychiatric topics.

Dr. Handratta: 0:35

My name is Dr. Handratta attending psychiatrist. I did my residency from University of Connecticut and then I did my fellowship from Georgetown University in consultation and liaison.

Thanh: 0:45

Each episode features interview style discussions that explore the intersection of the mind medicine and the human experience. Together we'll uncover the hidden why and the groundbreaking discovery shaping the psychiatric landscape. So grab a seat, warm beverage, tune in, and let's embark on this journey to unlock the mysteries of the human psyche. Only on The Y in Psychiatry.

Dr. Amayo: 1:12

Welcome back to the Y in psychiatry today. I think today, so after we've talked about all the side effects of SSRIs and SNRI, today, we are going down one more level on that step of algorithm, how to treat depression. And before I continue to tell you guys about that, I'm your host, Dr. Amayo Psychiatry, consult/liaison fellow. And with me as usual is Dr.

Dr. Handratta: 1:37

Hi, I'm Dr. Handratta. How are you guys doing?

Dr. Amayo: 1:40

They're doing well. I hope. If not, stop listening and call 9 1 1. And so we talked about the first step, right? The first step. Actually I'll say first step is, rule out medical causes. Make sure you have the right diagnosis, that it's not bipolar disorder. See if you can do some behavioral modifications and some psychotherapy. So you've done all that and then you, the next step, you start a SSRI or SNRI, depending on the patient factors. If you dunno what I'm talking about, go back a few episodes and you've done all that. And Say, I have a patient that I've exhausted all my SSRI capabilities, and yet they're still having symptoms of depression. Yeah. PHQ9 is still a seven and it came 98. I'm not getting good response. What should I do next?

Dr. Handratta: 2:27

Okay, so the next is if you want to be as happy as, uh, Miracle, get some sleep deprivation. Miracle just came back from Texas. He hasn't slept, but he got his license. Hi. Congratulations. Congratulations. Yeah. Yeah. So let's go to Y in psychiatry. So if you fail the first step, right? So then you go to step two in the algorithm. So step two is if you, basically the step one has been ineffective or you're not able to tolerate the medication from step one, right? So step one, we talked about SSRI, we talked about SNRI. We talked about bupropion, we talked about mirtazapine and vortioxetine as well as vilazodone. So suppose that you tried all these things you're not able to tolerate or the ineffective go to step two, but before going to step two, always make sure that the patient is adherent to the treatment, right? So compliance is very important. We have problem in with compliance in psychiatry. We have problems with compliance in any field of medicine. Especially if you go to a diabetic clinic or in hypertension clinic is the same thing, right? So always good to ask the patient, Hey, in a week how many times or in a month, how many times have you forgotten to take the medication? That's a appropriate question to ask the patient. So they will tell one or two days, right? Make sure that they're adherent to the treatment. The second thing that you need to actually make sure is that you have used the medication at a therapeutic dosage for a therapeutic period of time, right? But if you do not give like an adequate dosage trial and adequate duration trial, then the medication will be ineffective, right? The third thing is that make sure that your diagnosis is correct, right? Dr. Amayo already spoke about make sure that you've ruled out bipolar disorder and other. Comorbid psychiatric disorder. Then what we do is that if the patient has shown a partial response to the treatment not a full response, then we go with something called augmentation. So one of the augmentation strategies at psychotherapy, right? Like cognitive, behavioral therapy or interpersonal therapy. The second thing is, what you can do is you can actually augment with F D A approved atypical antipsychotics. So few of the F D A approved atypical antipsychotics is adding aripiprazole or brexpiprazole or cariprazine or quetiapine. We won't be actually talking about quetiapine in step two. We'll talk about it in step three because quetiapine is associated with metabolic side effects. Then if this is not work, then you basically augment the antidepressants with s ketamine intranasal spray. Or intravenous ketamine. Intravenous Ketamine is not FDA approved for depression, but esketamine is right. And the next strategy will be if they don't respond to es Ketamine or iv Ketamine is combination of antidepressants. So you can combine an SSRI with bupropion or you can combine an SNRI with mirtazapine. And the combination of SNRI with mirtazapine works very well in patients who have depression with anxious features. But please do not combine SSRI with SSRI or SNRI with SSRI or SNRI with SNRI because the risk of serotonin syndrome.

Dr. Amayo: 5:41

And SSRI with Trazodone as well is okay.

Dr. Handratta: 5:43

It is okay. Actually, SSRI with Trazodone, because the dosage of Trazodone that we use is very low, and you require at least like 70 to 80% blockage of the serotonin transporter to have the antidepressant effect of Trazodone. So your dosage has to be like above a hundred and. 15 milligrams. Yeah.

Dr. Amayo: 6:01

And so the next step in our algorithm for man management of depression, add a psychotherapy or you can add a antipsychotic. And it sounds like these three are the f D A approved ones with less risk. So aripiprazole, brexpiprazole, and cariprazine. These are the D2 partial agonist medications. And then esketamine and ketamine. We talked about ketamine in one of our other episodes. And then you can, do some combination of a SSRI or an SNRI with another medication with a different form, right? So that doesn't work. What next do we do?

Dr. Handratta: 6:38

So if that does not work, Then you go with step three. Step three, right Now, step three basically means that now this is a patient who may not be managed, who cannot be managed in a primary care clinic, right? Because most of the psychiatric patients, they see the primary care physicians actually for depression, right? We get like a small subset of those patients actually, who are not able to be treated with the primary care, come to psychiatry. Wait, are you saying even at step two, a PCM, a primary care, physician can prescribe an antipsychotic. Yes, they can. That's why actually we have something called collaborative care clinic. So now psychiatry is actually going towards collaborative care. So the collaborative clinic is a primary care clinic where you have a social worker or a nurse who is basically embedded in the clinic. So the primary care provider will see a case and they do a PHQ9 or a GAD7, or they do a PHQ2 or GAD2 and it comes positive. They refer the patient to see the case manager who's a social worker or a nurse. They will do psychiatric interview and at the end of the week, they'll call the psychiatrist. Discuss all the case. The psychiatrist will look at the medical, record, the labs, and look at the scales, and then we'll come up with a treatment. And the treatment is then actually sent in a format to the primary care provider who implements and writes a prescription. And then the case manager or care manager will follow up the patient. And this is collaborative care clinic. That's cool. So majority of the patients can be managed in a primary care clinic. Yeah.

Dr. Amayo: 8:16

Except when you get to step three.

Dr. Handratta: 8:18

Exactly. So step three is basically means that these patients have tried step one, tried step two, and they're still not responding to the treatment, or they've shown a partial response, right? Then you go to step three. So step three, you have to actually get the psychiatrist inward, right? If the psychiatrist is not already involved. Dun. Yes, exactly. Again, the same thing, right? You have to actually make sure that you have used a therapeutic dosage. For a therapeutic period of time, you have to make sure that the patient is adhere, adherent to the treatment. Make sure that you have not missed any medical problems which is causing the underlying depression or any other comorbidities, right? And then you basically, if you have ruled all those things out, then again you actually use other augmentation strategies. So in this augmentation strategy, combine an antidepressant with quetiapine and Tappin is used in step three because of the metabolic side effects. And then we will talk about actually, what are the things or the tests to be ordered actually when you prescribe an atypical antipsychotic. Next season. Yeah. Next season we'll do that. And then if this does not work, then you combine the antidepressants with lithium. Lithium, or with T3, which is also called cytomel. Because T three actually penetrates the blood-brain barrier better than T4. T four. So we use T3. The game plan here is actually to start T3, get a baseline before you start the T3. Get a baseline free T3 and TSH level.

Dr. Amayo: 9:47

So just to clarify, T3 thyroid hormone.

Dr. Handratta: 9:50

Yes. It's a thyroid hormone

Dr. Amayo: 9:52

But now levothyroxine medication.

Dr. Handratta: 9:54

So it is not levothyroxine.

Dr. Amayo: 9:55

So it's levothyroxine is T4 it's, yeah. So the T3? Yes. Oh wow. So it basically crosses the blood brain barrier. It crosses.

Dr. Handratta: 10:02

So that's what you need. And T3 augmentation works very well, especially in female population who have atypical depression. That's a population that will respond to T3. So the game plan is when you start T3 your game plan is to have the free T3 at the upper level of normal. Okay. And your T4 at the lower level of normal. Without any. Side effects. Side effects, like the patient should not actually have arrhythmias. And also make sure that you check the bone mineral density. What if their T s H is already. So what if the Ts H is already very low? So the baseline T3 or T4 is already maybe closer to the upper level of normal. Would you still do T3 then? You will not. You will not.'cause you do not want it to actually cross the threshold. Okay. Okay. So the Tsh it depends on the lab. It's actually 0.45 and low. Then I will not do it. Okay. Yeah. Then basically we'll go with other strategy. Okay. So the other strategy is combining the antidepressant with I do not know how well this works, but it's actually in the algorithm. So with L-methyl folate or Sami? Asil methionine. Now you have to understand that level one treatment, as placebo controlled trials, randomized controlled trials. So the level one we talked about has a lot of strong data. Level two also has data, but not as strong as level one. Level one, and level three is usually like case control studies. So they're not Right. So you're

Dr. Amayo: 11:27

Taking cowboy grain of salt.

Dr. Handratta: 11:29

Exactly. Exactly. So I don't want people to actually like, just prescribe. So, I want people to suppose that the combination of L-methyl folate or SAM-E does not work with the 90%.

Dr. Amayo: 11:40

Do we know why, what the theoretical we basically know actually that L-methyl folate and SAM-E basically works on your methionine cycle. So if you have a deficiency of, say, an enzyme actually in your folate cycle. Yeah. Then you can actually use this particular treatment, or they have a polymorphism in the enzyme, which is called as methyl tetra hydro folate reductase. Then this particular treatment may or may not work. The data is not too strong. But these are treatment resistant cases. Would you get a genetic test before you do it? Because I know there's a subpopulation that has that deficiency and they have a tendency towards depression and mood disorders. So would you get a genetic test before you do it?

Dr. Handratta: 12:29

Yes, I usually get a genetic testing done. Okay. And if I see that there's a polymorphism in the methyl folate reductase, then I'll add L-methyl folate to the combination. Okay. Yes. Right now, suppose that this augmentation strategy does not work, then you combine the antidepressant that is SSRI or SNRI, right? With ECT, we can use electroconvulsive treatment. The response rate is very high. We all know that ECT should actually be in level one, right?

Dr. Amayo: 12:57

In some cases.

Dr. Handratta: 12:58

Exactly, but we don't do that actually because of the cognitive side effects and the stigma that is associated with ECT, but it's one of the most effective treatment for treatment. Anti depression, right? Or you basically can use rTMS trans magnetic stimulation, right? Where you focus on the left dorsal, lateral prefrontal cortex, or basically you switch from an SSRI or SNRI to monoamine oxidase inhibitor. Oh, which a lot of psychiatrists are scared to touch, right? Or you switch them to tricyclic antidepressants. Which we don't use it that often. Neurologists use it for insomnia or for chronic pain, So this is the treatment strategy in level three. Level three.

Dr. Amayo: 13:38

And just to make sure we all get it, so you trial first with quetiapine, if that doesn't work, lithium try T3 depending on their thyroid hormone levels methylfolate and SAM in some certain populations. ECT is always an option in any of the steps. TMS as well. And then you start to think of mono oxidase inhibitors. And then if that doesn't work, call your local priest and Craig. No.

Dr. Handratta: 14:06

So step four is basically like you do three, have not actually tolerated level three, or you have developed side effects with the medications in level three. Then you actually go with step four.

Dr. Amayo: 14:18

So if you trial that and you call your local priest and that didn't help, then you go with step four. What do you do with step four? So step four is three antidepressant combination, right? So none of the data, again, is not very strong. These are case reports. These are not randomized controlled trial. I want the one people to know about it. So if everything has failed and the patient is not, Mable for E C T or R T M S, either because it's not available or it's too expensive, right? They cannot actually do intravenous ketamine because the insurance doesn't cover it. Or s Ketamine because the insurance doesn't cover it. So then, or it's too expensive, you only insurance covers. Then you go with step four. So step four is a three drug combination, right? So it's basically combining an SSRI or SNRI with Mirtazapine and bupropion. Or combining an SSRI or SNRI with mirtazepine and lithium, or combining SSRI or SNRI with bupropion plus atypical antipsychotic. And if this does not work, then you can use vagal nerve stimulation. That's another option that you have which is going to be an invasive procedure. But that should actually be the last option if nothing else. Helps the patient. So SSRI, N D R I and the atypical antipsychotic.

Dr. Handratta: 15:43

Yes. Yeah. Yes. So that's all actually regarding the treatment algorithm for major depressive disorder.

Dr. Amayo: 15:51

And that's all we have in today's Why in Psychiatry.

Dr. Handratta: 15:56

Happy Friday, guys. Happy Friday.

Katrina: 16:03

Thank you for joining us on today's episode. Our tireless team is already hard at work, cobbling together another potpourri of fascinating discussion for next week, so be sure to tune in, visit our website and our podcast feed and let us know your thoughts on the episode. Subscribe so you don't miss our releases every Wednesday. Until next time, keep smiling, keep shining, and stay curious.