Case 1: Newly Diagnosed Treatment Resistant Depression

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EP: 1.Case 1: Newly Diagnosed Treatment Resistant Depression

EP: 2.Case 1: An Overview of Treatment Resistant Depression

EP: 3.Case 2: Prescribing Intranasal Esketamine

EP: 4.Case 2: Starting a Patient on Intranasal Esketamine

EP: 5.Targeting the Glutamatergic System for Treatment Resistant Depression

EP: 6.Phase 3 TRANSFORM Trial

EP: 7.Intransal Esketamine and REMS

EP: 8.Health Care Requirements to be Aware of for Intranasal Esketamine

EP: 9.Advising Clinicians on Using Intranasal Esketamine

Lisa Harding, MD: Welcome to this Psychiatric Times® Case-Based Psych Perspectives titled “Managing Patients With Treatment-Resistant Depression.” I’m Dr Lisa Harding, a board-certified psychiatrist and a clinical instructor of psychiatry at the Yale School of Medicine in New Haven, Connecticut. Joining me is the esteemed Dr Angelos Halaris, a board-certified psychiatrist and a professor of psychiatry at Loyola University Chicago’s Stritch School of Medicine in Maywood, Illinois. The goal of our discussion is to share insights in diagnosing treatment-resistant depression [TRD] and reasons for inadequate treatment response with antidepressant therapy, as well as to provide a brief overview of available treatment options and to offer recommendations on how treat patients with this disorder. Welcome, Dr Halaris.

Angelos Halaris, MD, PhD, APA, ACNP, CINP: Thank you so much for inviting me. I’m honored by your invitation and glad to be here.

Lisa Harding, MD: It’s nice to see you again. We’ll start by reviewing a couple of case scenarios. The first case presentation, No. 1, is a patient newly diagnosed with treatment-resistant depression. A 26-year-old man with a history of major depressive disorder for over 7 years presents with complaints of trouble sleeping as well as feeling unhappy, worried, and fatigued. He gradually developed sleeping difficulty as well as low mood and loss of interest. He tried multiple treatments, including escitalopram, fluoxetine, venlafaxine, and bupropion. However, his symptoms weren’t fully relieved. He was subsequently diagnosed with treatment-resistant depression. The patient reports having an average childhood, being an average student, and having good relationships with coworkers and no problems at work. He was always involved in psychotherapy, and denied any drug or alcohol use.

My overall impression of this case is this is a young patient who’s supposed to be living the life actuation part of his life, and he has now tried and failed more than 2 antidepressants. One of the things coming to mind was, is he stopping these antidepressants because of adverse effects, as I see in my clinical practice? What was the adequate dose of the adequate trial in terms of these medications that he was prescribed? Dr Halaris, what are your overall impressions of the case?

Angelos Halaris, MD, PhD, APA, ACNP, CINP: Much like what you just said, Lisa, as presented, this brief case scenario leaves many more unanswered questions, some of which you already touched upon. I’d like to reinforce your own questions and add a few of mine as well. First and foremost, what kind of work-up was done prior to diagnosing the patient and then treating him with the list of mainly SSRIs [selective serotonin reuptake inhibitors] and SNRIs [serotonin and norepinephrine reuptake inhibitors]? By that, I mean where other factors that are known to contribute to depression, and especially TRD, had they been carefully assessed by means of a thorough psychiatric diagnostic evaluation and the pretty much established blood work that we know is essential, such as ruling out endocrinopathies, assessing HPA [hypothalamic-pituitary-adrenal] function, looking at diabetes, inflammatory conditions, any chronic medical illnesses that invariably lead to chronic inflammation, including neuroinflammation. Because if there’s an inflammatory focus elsewhere in the body, these pro-inflammatory substances known as cytokines invariably make their way into the brain parenchyma and stimulate microglia and astrocytes to also become inflamed. So we have a relocation of the peripheral inflammation into the brain leading to neuroinflammation. These are all factors that I’d like to see addressed.

Other issues are obviously vitamin deficiencies, notably vitamin D, especially during the winter months. But this also happens in summer months in susceptible individuals. I’m amazed at the frequency of vitamin D deficiency, including in young people. Unless we make a point to check these issues routinely at the initial evaluation, some of the symptoms of vitamin D deficiency resemble symptoms of depressive disorder with anxiety, low energy, low motivation, sense of desperation, attention-focusing issues and so on. The good news is that it’s fixable by administering the right supplementation of vitamin D.

This transcript has been edited for clarity.