Clinical Implications and Potential Benefits of Newer Treatments for Depression

In part 2 of this series on the future of depression and treatment-resistant depression (TRD) interventions, Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRN, and Kristian Dambrino, DNP, PMHNP-BC, touch on the clinical implications of several newer depression treatments. The clinicians first discuss the promise of zuranolone and bupropion-dextromethorphan in providing rapid-acting relief for patients, particularly for those who have been discouraged by previously unsuccessful interventions. They then dive into the nuances of using ketamine and esketamine as adjunctive therapies for TRD. 

From considering intervention cost to ensuring thorough patient education on potential side effects, Carbray and Dambrino provide a comprehensive overview of the factors clinicians should assess as they integrate these newer medications into their patients’ treatment plans.

Catch up on part 1: The Role of NMDA and AMPA Receptors in Rapid-Acting Antidepressant Treatments

For more news and expert insights on depression, visit Depression Care360.

Read the Transcript

Julie Carbray, PhD, PMHNP-BC: Hi, I'm Julie Carbray, nurse practitioner and clinical professor of nursing and psychiatry at the College of Medicine Department of Psychiatry and the College of Nursing at the University of Illinois, Chicago. 

Kristian Dambrino, DNP, PMHNP-BC: And I'm Kristian Dambrino, a psychiatric nurse practitioner and founder of Dambrino Consulting and Wellness, and I practice in Nashville, Tennessee. 

Carbray: So, some clinical implications of newer treatments, Kristian, are offering promise about more rapid approaches. I'm thinking about zuranolone. Not only is the mechanism of action something different, it's a steroid medication, a neurosteroid. And this, again, acts differently from a mechanism of action in setting quicker relief from depressive symptoms. For women who are in their third trimester of pregnancy and are looking for a quick relief all the way through to postpartum, now zuranolone is an oral agent that will offer that relief, sometimes within a couple of days. [It] can be used short term and really lift that depression at a very important period of time where we want symptom reduction because of risk involved. 

Now, there are other newer agents with mechanisms of action that you have talked about as well. 

Dambrino: Right. And so, we also have to think about, why would we want a medication to work in that time frame? If I'm working with a patient who's having trouble getting out of bed or having trouble just with basic day-to-day activities, we need that to improve quickly, ideally. A medication like bupropion-dextromethorphan, for example, is not Food and Drug Administration (FDA)-approved for treatment-resistant depression, but can work within 1 week, so patients can see improvement early on. When patients have tried different medications over time, they're really discouraged, and they're not used to seeing results in a shorter time frame, if there is a possibility of [a medication working within 1 week], and maybe even a pro-cognitive benefit—again, when we're talking about neuroplasticity, synaptogenesis, and that's really involved in the glutamatergic pathways—this could be really exciting. We don't want to make false promises to patients, but if this is a possibility, it's certainly a treatment that we should be offering. 

Carbray: Well, and I think we're wanting, as clinicians, to turn things around as quickly as we can so that there's some hope in our treatments that we're helping to deliver along with our patients. Ketamine and esketamine are among those treatments, and I know that you are using a bit of that in your practice. [Is there] anything you want to say about that treatment and how it may help with turning symptoms around in the short term or long term? 

Dambrino: If we think about what patients ketamine or esketamine are right for, ketamine is not an FDA -approved treatment, so we do want to make sure patients have the financial means to pay for it and that they're able to have transportation to and from appointments; this would also apply to esketamine. Now, esketamine is FDA-approved for treatment-resistant depression as an adjunct to an antidepressant that patients are already taking. 

Carbray: So it's not just, “take esketamine, and that will be your be your only agent.” Typically, it's on top of an antidepressant that the patient may be taking already.

Dambrino: And again, we want to make sure that they do have the support system where they're able to attend treatment and they're able to follow up. 

Carbray: What about that dissociation we see sometimes as an effect of ketamine, esketamine? 

Dambrino: We want to make sure that this is a really crucial part of our patient education, when we're thinking about trauma-informed care, that patients understand [that dissociation is] a possibility and that they have the support around them, whether we are talking about support staff, but also just processing that with them and holding space. Everyone will experience this to different degrees, but it is certainly a possibility, and we want to make sure that patients are ready for that.

Carbray: Yeah, and if not, it can come as quite a surprise. The other element too, that we've talked about, is that although depressive symptoms can improve very quickly, within a day, sometimes a couple of days. Sustained depression relief is something we're still trying to understand. How many treatments are required, and for what amount of time, because long-term data is still rolling in. 

Dambrino: Right. And so for esketamine, which again is FDA approved as adjunct for treatment-resistant depression, typically patients will go twice a week for treatments for the first month, and then the next 4 weeks they will go maybe once weekly, and then after that maintenance treatment can be different. It can also depend on what insurance will cover. So again, we have to think about, how does this fit into the patient's daily life and what they're able to pay for as well. 

Carbray: Kristian, thank you so much for this great conversation about treatment-resistant depression and building hope for our patients about new mechanisms of action. 

Dambrino: Absolutely. Thank you. I've enjoyed meeting with you and I've really enjoyed learning as well.

Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRN, holds her PhD (93) and Master of Science (88) degrees from Rush University, Chicago and her Bachelor of Science (87) degree from Purdue University in West Lafayette, Indiana. A clinical professor of psychiatry and nursing at the University of Illinois Chicago and the director of the Pediatric Mood Disorder Clinic, she has been practicing as a Psychiatric Nurse Practitioner for over 35 years.

Kristian Dambrino, DNP, PMHNP-BC, is a board-certified psychiatric mental health nurse practitioner and the founder of Dambrino Wellness, an outpatient mental health practice in Nashville, TN. She received her Doctor of Nursing Practice from Belmont University College of Nursing, with a focus on innovative global nursing partnerships in Indonesia. Having worked extensively with severe and persistent mental illness in community mental health and crisis settings, Dambrino embraces a trauma-informed, evidence-based prescribing model for her patients.

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