Thinking Beyond Monoamines in Depression Treatment

While conventional antidepressants are central to depression care, associated side effects, delayed onset, and residual symptoms remain a concern for many patients. 

In this video, Veronica Ridpath, DO, Psych Congress Elevate faculty member, discusses how evolving understanding of the biological pathways involved in depression is changing the landscape of treatment approaches. Dr Ridpath first reviews the key limitations of traditional monoamine-based therapies. She then highlights how emerging options are leveraging different mechanisms of action to achieve greater functional recovery and faster relief for this patient population. 

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

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Key Takeaways for Clinical Practice: 

• Conventional antidepressants targeting monoamine/serotonergic pathways may have intolerable side effects, delayed onset, and residual symptoms (eg, anhedonia), limiting functional recovery and quality of life despite symptom dampening.
• Evidence suggests monoamines represent only part of the disease process; emerging understanding includes roles for neuroplasticity and neuroinflammation, indicating limits of monoamine-only mechanisms.
• Episodic, patient-centered treatment approaches rather than continuous daily maintenance may reduce side-effect burden, improve adherence, and better align care with symptom periods.

Read the Transcript:

Veronica Ridpath, DO: My name is Dr Veronica Ridpath. I am a general and addiction psychiatrist. I am also the department chair of psychiatry and substance use disorders at HopeHealth in Florence, South Carolina. 

Psych Congress Network: What are the key limitations or challenges of conventional antidepressants?

Ridpath: Some of our limitations of traditional antidepressants is that often patients will have to deal with intolerable side effects—maybe the medications take longer to work than is really feasible with their life—and there can be residual symptoms that still impact their quality of life. Our traditional antidepressants that work on these serotonergic pathways are really good at dampening the negative experience but oftentimes don't do as much for bringing back quality of life and bringing back function. 

Anhedonia is definitely a residual symptom that we often see, and patients have to wait long periods of time as they adjust to medications and see what their therapeutic effect is going to be. Oftentimes they do lose a lot of time in waiting for effect, and we may not even get them to the functional improvement that they want.

PCN: How do traditional mechanisms of action compare to those of emerging treatment options?

Ridpath: Some of the traditional mechanisms of action that we have are more based on the monoamine pathways, and the more information we get about depression—the pathogenesis, the progression of depression—monoamines are [just] one piece of the picture. 

There is an emerging body of evidence that there may be issues with neuroplasticity, issues with neuroinflammation, and oftentimes when we are taking patients or looking at studies and just reducing the monoamine effect, it doesn't traditionally cause depression. So, we know that there's more pieces to that puzzle. 

As we get more information, we're starting to realize that we need to start looking at other treatment options and other explanations for the pathogenesis of depression.

PCN: Are there any emerging treatment options that you’re particularly excited about? 

Ridpath: I think most of my patients would say that they are most excited about episodic treatment of depression versus the daily maintenance medications. It's more patient-centered. It's something that we can look at treating when we're having symptoms, not necessarily having to deal with the side-effect burden all of the time, in that attempt to prevent relapse. I'm excited for anything that helps my patients be more adherent and get a better quality of care from their depression treatment. 

PCN: Are there any misconceptions about emerging treatment options that you’d like to clarify for our audience?

Ridpath: I think with some of the emerging treatment options, we just don’t have as much information out there as to how they’re different from traditional mechanisms of action. 

Those of us who are going to conferences like Psych Congress and get that information from some of these great leaders in the field have that understanding, but I think that our general clinician [population] hasn’t had that exposure yet. So, as we’re changing that paradigm of, “depression equals serotonin or dopamine or norepinephrine,” we’re going to have to really focus on the education of what does it look like to treat depression in a different way. 

Thank you for joining me today. I hope this was helpful for your clinical practice.

Veronica Ridpath, DO, serves as Department Chair of Psychiatry and Substance Use Disorders at HopeHealth in Florence, SC. She is board certified in General Psychiatry and Addiction Medicine. She also serves as Associate Clinical Professor, Department of Neuropsychiatry and Behavioral Science at the University of South Carolina- Columbia and teaches medical students and residents in her clinic. She graduated from the Edward Via College of Osteopathic Medicine in Spartanburg, SC and completed residency in Psychiatry at Atrium Health in Charlotte, NC. She has a special interest in integrated substance use treatment and improving access to psychiatry services in rural and low resource environments.

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