When Is It Time to Adjust Treatment for MDD?

When first-line antidepressant therapy provides only partial relief from major depressive disorder (MDD), when should clinicians consider changing course?

In this video, Julie Carbray, PhD, PMHNP-BC, FAAN, Co-Chair, Psych Congress NP Institute, discusses how persistent difficulties with motivation, cognition, relationships, and day-to-day functioning can signal an inadequate treatment response—even when mood symptoms have improved.

Drawing on findings from the STAR*D trials, Carbray examines the prevalence of partial response, considerations surrounding switching versus combination treatment, and the potential role of serotonergic and dopaminergic mechanisms in addressing residual symptoms. She also explains why clinicians should look beyond core depressive symptoms when evaluating progress toward remission.

• MDD partial response was common in STAR*D, with about 30% of patients achieving full symptom relief; persistent problems with motivation, cognition, relationships, and daily functioning may indicate inadequate response.
• Switching antidepressants may offer limited improvement, according to Carbray’s discussion of STAR*D, while combination treatments showed more robust response and remission rates.
• MDD treatment assessment should extend beyond sadness or mood. Carbray emphasize residual functional impairment and discussed serotonergic and dopaminergic pathways relevant to reward processing, motivation, cognition, and mood stability.

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: When should clinicians consider adjusting treatment strategies in patients with MDD when first-line antidepressant therapy is yielding only partial relief?

Carbray: Well, we know from the STAR-D trials that partial relief of symptoms is pretty common. In those trials, the data really showed only about 30% of patients really had full relief from depressive symptoms, so it leaves a huge gap with partial responders. That gap is really a challenge with our patients because they need to work, they need to maintain their relationships, and while some of their symptoms have shown response, often it's symptoms like motivation, cognition, and overall functioning, that really get in the way. So, waiting rather than acting can really be a disadvantage for our patients.

We also know from those trials that switching agents might improve that number a little bit, but it's not substantial. Combination treatments really have more robust response rates and actually also remission of illness rates. Not only do we want to call out those symptoms that continue to remain with a partial response, we also want to act quickly and evaluate whether moving towards a combination therapy might result in a better response rate and improved remission rate.

PCNPI: What are the key indicators of inadequate treatment response?

Carbray: Key indicators of an inadequate treatment response really reflect overall functioning: ability to perform day to day activities like remembering the groceries on the way home from work, even having the inertia to get up and go to work. So, it's just not cognition, it's also connecting with other people, it's motivation--you're not really hearing about sadness here, are you? Sadness or mood per se, but the reverberations around mood that really can keep functioning impaired.

PCNPI: Can you briefly describe the mechanisms of action and latest clinical data on FDA approved and emerging atypical antipsychotics that may be considered for combination treatment?

Carbray: This is really some newer thinking around looking at partial dopamine antagonists and agonists to offer some relief along those pathways and looking at reward processing, motivation, again, some of those ripples around depressive symptoms where we usually have thought about depression treatment being more of the serotonergic symptoms.

We typically have thought about the neurotransmitters impacting the serotonergic pathways as being the crux of what can help with depressive symptoms. Partial dopamine agonists can also, in combination with some of the serotonergic pathways, like 5H2A antagonism, 5H2AC antagonism, really looking more at serotonergic pathways in combination with dopamine activity, are really beginning to demonstrate some hopeful additions to typical antidepressant therapies. So, that combination together can hit at the reverberation of symptoms beyond what we see as DSM-5 core symptoms of depression and looking, again, at functioning along pathways that offer more promise to our reward systems, cognition, and mood stability in ways that can impact functioning.

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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