Steven P. Levine, MD

We’ve covered a lot of ground here today. I want to thank everyone for this rich and informative discussion. Before we conclude, I’d love to get final thoughts from each of you. Perhaps we can start with you, Angelos.

Angelos Halaris, MD, PhD, APA, ACNP, CINP: 

Thank you. This was a great idea and a great panel. It’s too bad we didn’t have 6 hours or longer to get more in depth about these very apt questions and issues you raised, Steve. I’d like to conclude by saying we need to help the public, including our patients and colleagues, raise their level of awareness of depressive illness in general, and the state of the art about what we can do. I’m not going to use the word pandemic because it has a different connotation, but it’s a very widespread problem worldwide.

Thanks to the [COVID-19] pandemic, the latest statistics as reported by the AMA [American Medical Association] a couple of days ago showed that of those who have been infected with COVID-19, about a third of them go on to develop clinical depression, anxiety, possibly substance abuse, suicidality, and even neurological sequelae. We have a serious situation here, and it behooves us to make the public and our colleagues—psychiatric and more so nonpsychiatric colleagues—aware that we have a real problem. There are a lot of things we can do. We’ve got to work as a team. We have to be cooperative and open-minded. Doing anything we can to help our patients be safe, get better, and have a life offers the best gratification of my entire career.

That’s an important message, Angelos. Hopefully this discussion we’re having today that will be shared with our colleagues will go some distance toward accomplishing that. Thank you. Lisa, do you have final thoughts?

Yes. Somewhat riffing off of what Angelos said, before the COVID-19 pandemic, the WHO [World Health Organization] said that in 2020, depression would be the leading cause of disability. That was before the pandemic ever happened. It’s 2021; no new data are out there, but each of us can hazard a guess as to where major depressive disorder lies. The overarching message for me is of love and patient-centered care. We’re living in times where there’s heightened sensitivity to everything. There’s a lot of talk in the community about who should be delivering care and what kind of care. But at the end of the day, each of us has made a commitment to mankind to help end suffering. If we keep that first, we’ll all make the world a better place.

Those are beautiful sentiments, Lisa. Thank you. Patricia?

 I definitely agree with what my colleagues have said here on the panel. We really need to look at integrative care. Because depression is going to be so much more prominent in the next 5 to 10 years, we need to look and be able to identify patients who are suffering from depression and start treatment earlier. One of the biggest issues is that treatment is withheld and not started earlier. That’s why we’re seeing so many patients who later are resistant to medication as well. Refer early, educate yourself, and please don’t be scared of the new treatments we have: racemic ketamine, esketamine, and all the other things coming down the pike that we are very excited about. Don’t be afraid. Educate yourself. Know that there are other treatment options for your patients, and they deserve to be considered if they’re the right patient.

Thank you, Patricia. Thank all of you. And thank you for watching this 

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Closing thoughts regarding a discussion on improving the management of patients with treatment-resistant depression using newer treatment approaches in a more standardized fashion. 

Integrated Care and Treatment-Resistant Depression 

 Let’s come back to TMS [transcranial magnetic stimulation] and ECT [electroconvulsive therapy], sticking first with first-line therapies with all the classes of medications and adverse effect profiles Patricia discussed. There are many examples of antidepressants that fall under each of those classes. Can any of you speak to what factors you consider when choosing a first-line antidepressant? What causes you then to potentially switch therapies either within a class or across classes?

Angelos Halaris, MD, PhD, APA, ACNP, CINP:

 Yes, I’d be happy to start by saying what I’ve increasingly been doing. Since the era of pharmacogenomic testing, I’ve become a proponent. I’ve seen excellent results with treatment-resistant depression in particular. Where appropriate, I do it from the get-go before the trial and error and hit or miss approach. That guides me in choosing what medication would be congruent.

In the absence, reluctance, or inability to cover the cost of this testing, depending on the symptom profile, do I need more of an activating or sedating antidepressant? That gives me flexibility to pick and choose between something more serotonergic vs more of an SNRI [serotonin-norepinephrine reuptake inhibitor], like desvenlafaxine, which I like because it’s tolerated extremely well and does not lead to excessive sedation. If anything, it gives patients some energy and uplifts their mood. There’s even an antianxiety component, although it’s not very prominent. That’s the approach I take. I like MAOIs [monoamine oxidase inhibitors], especially the patch, selegiline, which is a great drug. I like it a lot. But for whatever reason, it’s not first line, for better or for worse.

Sadly, as we talked about earlier, no matter what approach you take, there’s a high probability that patients will not adequately respond to treatment at some point, hence the high rates of treatment resistance. Lisa, in those cases, would you like to address when you think about potentially referring patients for ECT or TMS?

Yes. This hits home for me. Just before I graduated, I used to teach ECT to the medical students at Yale [University School of Medicine]. The first thing you have to talk about is getting over the stigma of One Flew Over the Cuckoo’s Nest. Once you get that out there and you get Jack Nicholson out of the way, this is a great treatment. Where does it fit into the algorithm? That’s the question. If we’re speaking about things like catatonia and psychosis, it’s a different conversation than where ECT fits into the algorithm of treatment-resistant depression. With anybody who has treatment resistance with psychosis, this is automatically my go-to.

One of my good friends and training buddies in residency was like, “I’ll just tattoo ‘ECT me’ on the inside of my arm if this ever happens to me,” because of that rapid alleviation of the symptoms. Also, for pregnant women who are acutely suicidal, this is the go-to I would use. I’m now a little more conservative with my younger patients with regard to the cognitive [adverse] effects. I’m thinking about TMS or a form of ketamine when I’m thinking about other forms of depression outside of psychosis and women who are acutely suicidal in pregnancy. Those are usually the ones I think of first.

Insight regarding proper timing to initiate electroconvulsive therapy to help manage depression. 

Electroconvulsive Therapy for Depression 

 Patricia, in your practice, if you’ve evaluated a patient whom you’ve diagnosed with depression, and you feel that a pharmacological option is appropriate, what are the traditional classes of antidepressants? What does their adverse-effect profile typically look like?

We have the SSRIs [selective serotonin reuptake inhibitors], which are the ones that most people go to first. Primary care physicians are usually the ones who go to them first. That’s usually the first-line treatment for most patients when they first come in if they have a major depression disorder, not treatment-resistant depression. They have a lot of adverse effects. There can be sedation. There can be issues with hypernatremia. I’ve seen patients experience that. The thing is that not all of them work the first time. We talked about that earlier in this conversation. We usually treat them with a first-line antidepressant. We also have SNRIs [serotonin-norepinephrine reuptake inhibitors] such as Effexor and Wellbutrin in our armamentarium. We usually treat them for 4 to 6 weeks. At adequate dose and treatment, it sometimes doesn’t work, so we switch to another class.

There are other things, such as tricyclics, which are the older ones and not used as much anymore, or the MAOIs [monoamine oxidase inhibitors], which most of the young physicians don’t use. They don’t have that specialty in using them, so they stay away from them, but they do work well for patients with depression. Then we have augmentation strategies. We augment with things such as lithium. There are also antipsychotic medications. Atypicals are also used for augmentation therapy.

There are these other things that we use. But usually when a patient comes to me with treatment-resistant depression, all these things have already been exhausted and used. This is when we turn to something like esketamine or ketamine or look at things like TMS [transcranial magnetic stimulation] or ECT [electroconvulsive therapy]. Because at this point, they’ve really struggled with this illness. They have all these other issues happening in their lives. Maybe they can’t get up to go to work, are having problems at home with their families, or can’t take their kids to school because they’re getting so depressed. That’s when it’s time to use something else, and we use these other modalities.

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Dr Patricia Ares-Romero highlights the traditional classes of antidepressant therapies available, reacts to common treatment-related adverse events, and describes when each type of therapy is most appropriate within a patient’s treatment course. 

Traditional Classes of Antidepressant Therapies 

 Let’s transition to discussing other treatment approaches for depression. Angelos, can you talk a little about first-line treatments? Do you tend to use psychotherapy as a first step in treatment? If so, do you use psychotherapy alone? Do you recommend it along with pharmacological treatment?

 Excellent question. First, it all depends on the initial evaluation, which I like to make as thorough as possible. It’s certainly not a 20- to 30-minute initial assessment. That’s a nonstarter. It’s 45 to 60 minutes, possibly with a follow-up to complete the initial evaluation if necessary. I really want to make sure I understand what the patient is going through. What life circumstances do they have to cope with? What are the stressors in the patient’s life? What’s their history? All these are factors are very important and will guide me as I choose the treatment approach.

For the most part, I consider medication a top priority, but not exclusively. I am a staunch proponent of combination treatment with a psychotherapeutic modality concomitantly in the same session. It may just be a matter of supportive and educational therapy, providing a listening ear, showing empathy and compassion for what the patient is going through, and giving them hope where hope is appropriate without misleading them and giving false promises. I want to see them frequently at the beginning, not, “Here’s a prescription. Nice knowing you. Come back in 3 to 6 months.” That’s malpractice in my view.

Very often, I choose intensive psychotherapy, depending on the situation and what the patient is also struggling with. I had the fortune of being trained in some kinds of intensive dynamic psychotherapy, and I still apply it as appropriate. If the patient is interested in embarking on it, that could be as often as once a week or once every other week. At the very least, a monthly supportive therapy for the first 4 to 6 months is my modus operandi.

Lisa Harding, MD: My approach is a little different. I have an MA [medical assistant] who’s an E-RYT [Experienced Registered Yoga Teacher] 500-hour teacher. Before the infusion or insufflation, my patients all undergo an introduction to mindfulness meditation, and they have a 10-minute body scan, exercise, and meditative process before they undergo their procedure. This came out of papers that talked about psychotherapy. There’s this psychedelic thing that happens with ketamine that we really can’t quantify or tap into. We’re talking about this really unconventional approach with this new treatment. It leaves a lot of questions unanswered and ready to be answered.

If you have a major depressive disorder, it’s your first episode, and it’s mild, psychotherapy might be the thing. I primarily treat people with treatment-resistant depression, so we’re usually starting an intervention modality. I give patients some grace in starting psychotherapy because I don’t want somebody with a MADRS [Montgomery–Åsberg Depression Rating Scale] of 32 who’s struggling and has been failed by these conventional medications to then engage in psychotherapy, which is sometimes really taxing. I show them some grace. Sometime midway through the treatment, they start psychotherapy.

The appropriateness for initiating psychotherapy, either alone or in combination with other therapies, as frontline treatment for depression. 

Steven P. Levine, MD

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