Adjunctive MDD Treatment: Matching the Strategy to the Patient

How can clinicians individualize adjunctive treatment when antidepressant therapy alone does not achieve remission in major depressive disorder (MDD)?

In this video, Julie Carbray, PhD, PMHNP-BC, FAAN, Co-Chair, Psych Congress NP Institute, discusses factors that can guide treatment selection, including adverse-effect profiles, neurotransmitter activity, patient needs, and medication access. She explores practical barriers to adding second-generation antipsychotics (SGAs), including patient concerns, formulary coverage, stigma, and monitoring for adverse effects such as sedation, movement symptoms, and weight gain. Carbray also highlights dosing considerations for adjunctive medications, using aripiprazole to illustrate why clinicians may start with lower doses and titrate more slowly when targeting residual depressive symptoms.

• MDD adjunctive treatment should be individualized by considering adverse effects, medication characteristics, and patient needs; Carbray highlights sedation, weight gain, and serotonergic, histaminergic, and dopaminergic activity as considerations.
• SGA implementation can involve multiple barriers, including patient acceptance, formulary access, stigma, drug-drug interactions, and monitoring for sedation, movement symptoms, and weight gain.
• Adjunctive SGA treatment may utilize smaller dosing increments, with Carbray recommending lower starting doses and slower titration than when these medications are used for other psychiatric disorders, such as psychosis or bipolar disorder.

Julie Carbray, PhD, PMHNP-BC, FAAN: Hi, I'm Julie Carbray. I am a clinical professor of nursing and psychiatry at the University of Illinois--Chicago's Institute for Juvenile Research, Department of Psychiatry, and I'm also a psychiatric mental health nurse practitioner.  

Psych Congress NP Institute (PCNPI): How can clinicians determine what adjunctive options are the best for their patients with MDD?

Carbray: There are several adjunctive options for our patients. The first would be to combine an selective serotonin reuptake inhibitor (SSRI) with an serotonin-norepinephrine reuptake inhibitor (SNRI). We know that we see a little bit of improvement in depressive symptoms. Although there have not been head-to-head trials, there are for specific agents combining an SNRI versus an SGA—a second generation atypical antipsychotic—we are seeing some enhanced effect when you combine some of our FDA-approved and emerging agents to an antidepressant as a combination therapy. There are several that are out there. They all have different profiles around where they act and how robustly at which transmitters.

So, some of that also impacts adverse effects. Some effects we'd like to see, like maybe sedation, would be beneficial for our patient. We might then choose an agent where sedation might be a complement to what they need for their overall functioning. Some adverse effects may be less weight gain. In some of our newer agents like cariprazine and lumateperone, there's a more favorable weight gain profile, meaning patients are gaining less weight than on some of the other agents. And then on other agents, we might propose that there might be more enhanced cognitive benefit, again, because of how the neurotransmission affinity is on that particular neurotransmitter.

So, we want to take a look across adverse events, across potency, at which of the transmission sites, whether it's serotonergic or histaminergic or dopaminergic, and really determine for our patient what might be the best agent.

PCNPI: What are current challenges and or barriers to implementing adjunctive treatment options in psychiatric practice?

Carbray: As a prescribing clinician, somebody who has medications in my pocket to help my patients, I'm always very hopeful that one-stop shopping can happen. One agent cares for the full array of symptoms and the patient's only taking one pill to help them into recovery and remission. Sometimes that can happen and that's when I feel like I've really got it down. More often, it does not happen. We may have partial response, the patient is tolerating a medication well, but there are still symptoms that we're hoping to capture from improved treatment. The patient may have psychotherapy, a whole well-grounded array of treatment options, but we're still not there.

So, one of the challenges is having a conversation about adding in additional medication that will not be in conflict with the first medication or offer any drug-drug interactions, but might actually potentiate some of the response that we saw with the first agent. I think the first challenge is having the patient consider adding a medication to their repertoire.

The second is providing hope that this medication, especially when we're talking about adjunctive second-generation antipsychotics (SGAs), this medication may actually see some benefit earlier than the initial medication did where we had to wait a couple of weeks and then see are they having a good response or not. So, we might be able to accomplish that first challenge of adding another pill to maybe providing some hope that symptom reduction may be coming along quicker than what we originally imagined.

Maybe the third challenge would be access to the newer agents that are out having formularies that cover those agents for adjunctive treatment of major depression, covering adverse events and assuring patients that although SGAs are typically antipsychotics, they're not being used for psychosis, they're being used for depressive symptoms.

The fourth would be those adverse events that come along with this group of medications and talking with our patients about what we'll watch for and continue to monitor things like sedation, any movements they may see, and also adverse events, things like weight gain.

I think I'll add a fifth, and that is we all know when patients are engaged in treatment for their depression, they really need some hope. By the time they get to see somebody like us, they may have been on an antidepressant or a second antidepressant. Building some hope that we can see some good results, even with lower doses than we typically use with SGAs generally, is also important.

So, I would say those are 5 elements that I see as challenges. But I think as clinicians, if we can really learn about these agents and about how they may benefit our patients, we're going to see some robust effects.

PCNPI: Are there other factors clinicians should consider that may help ensure success when implementing adjunctive treatments?

Carbray: Probably the number 1 factor that clinicians should consider is what your range of dosing will be on FDA-approved adjunctive medications for those residual symptoms of depression. I'm going to use aripiprazole as an example. We know that efficacy in adding aripiprazole as an adjunctive medication, we're looking at dosing that's like 2 mg, 5 mg, maybe 10 mg at tops. Whereas if we're looking at using this agent for depression, bipolar depression, psychosis, we're actually going to be at much higher doses. And so one point you should consider is your dosing. You're going to start at lower doses and likely go slower than you would if you were using these treatments for other disorders across psychiatry.

I'm Julie Carbray. Thanks so much for joining us to talk about this important topic for all of us trying to help our patients. I hope it's been helpful in trying to help you to think about your best treatments for our patients we're all serving. I look forward to another conversation soon about how we can continue to partner for the best of our patients.

Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, FAAN, holds her PhD and Master of Science degrees from Rush University, Chicago. A clinical professor of psychiatry and nursing at the University of Illinois Chicago, she has been practicing as a psychiatric nurse practitioner over 35 years. As UIC faculty, Dr Carbray teaches course content in psychopharmacology, mood disorders, and development and therapeutic interventions with children and adolescents for students across various multidisciplinary programs. As the Director of the Pediatric Mood Disorder Clinic, Dr Carbray leads the clinical program and multidisciplinary training and is a nationally recognized clinical expert in children and adolescents with mood disorders.

Dr Carbray holds a national reputation of excellence in serving families of children with mood disorders and was recognized with the UIC Preceptor of the year award, the Karen Gousman Excellence in Nursing Award, the American Psychiatric Nurses Association Best Practices in an Outpatient Program for Bipolar Disorder Award, the UIC Inspire Award, the APNA Distinguished Service Award and the Susan McCabe psychopharmacology lectureship from the International Society of Psychiatric Nurses.

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