Key Takeaways Key Takeaways
  • 2024 Breakthroughs in Depression Treatment: Exxua™ (Gepirone), approved by the FDA in September 2023, has been a game-changer in managing Major Depressive Disorder (MDD), offering a novel mechanism of action with limited side effects.

  • Tried-and-True Medications: Established antidepressants like escitalopram, bupropion, and sertraline remained staples in 2024 due to their effectiveness, accessibility, and favorable side effect profiles.

  • Innovative Treatments for 2025: Zuranolone (Zurzuvae) stands out as a breakthrough oral medication for postpartum depression, addressing significant barriers posed by earlier treatments.

  • Personalized, Evidence-Based Care: Emerging antidepressants like Aticaprant, which target novel biological pathways beyond serotonin and norepinephrine, offer hope for individuals who have not responded to traditional depression treatments.

What’s New in Antidepressant Medications in 2025? 

The year 2024 marked a pivotal moment in the treatment of Major Depressive Disorder (MDD), as significant FDA-approved medications entered the market alongside new FDA approval filings, signaling exciting advancements in depression care. Among the highlights was Exxua (Gepirone), a groundbreaking medication approved in September 2023, which has opened new possibilities for both patients and providers. This innovative treatment, alongside other developments, has significantly altered the way clinicians approach medication management for MDD. In this article, LifeStance psychiatrists reflect on which treatments worked best for their patients in 2024 and share their insights on the promising new medications they anticipate in 2025.

Medication Management For Depression 2024: Tried, True, and Transformative

Despite the introduction of groundbreaking medications in 2024, many clinicians found themselves relying on well-established antidepressants for their effectiveness and accessibility. According to Dr. Stephon Martin, MD, escitalopram (commonly sold under brand names Lexapro and Cipralex and bupropion–marketed as Wellbutrin, Zyban) remained staples in his practice due to their favorable side effect profiles and diverse mechanisms of action.

“I prefer escitalopram for a number of reasons. Many have found that initial side effects such as GI distress are less intense. Additionally, it interacts with far fewer medications/substances than most, making it less complicated to add to a person’s medical regimen. Bupropion has a different mechanism of action than SSRIs, helping in slightly different ways. In addition to its potential benefits on mood, many find that it provides a boost in energy/wakefulness and enhances concentration/focus. Unlike SSRIs/SNRIs, it is not typically associated with sexual side effects and can even be useful in decreasing the severity of such symptoms when taken concurrently.”

Similarly, Nicholas Cunningham, PMHNP, highlighted sertraline (Zoloft) as his go-to choice, noting its ability to address depression alongside various anxiety disorders. “For much of 2024, as I was seeing a lot of new patients, sertraline (Zoloft) was my drug of choice for its ability to aid in not only depression but varying types of anxiety from agoraphobia to public speaking. I saw a lot of improvement in the lives of many of the patients that not only stayed with the medication regimen but also made a concerted effort to make the appropriate changes in their lives to bring about more positive change and not just be spectators to their mental health.”

I saw a lot of improvement in the lives of many of the patients that not only stayed with the medication regimen but also made a concerted effort to make the appropriate changes in their lives to bring about more positive change and not just be spectators to their mental health.

-Nicholas Cunningham, PMHNP

Dr. Areum Kim, MD, a psychiatrist specializing in children and adolescents, emphasizes the value of relying on tried-and-true medications to avoid potential barriers for her patients. “Although new medications can be exciting and innovative, they are often expensive and difficult to access,” she explains. For younger populations, well-established options like Prozac, Lexapro, and Zoloft remain her preferred choices because they often offer effectiveness and accessibility without the challenges that can come with newer treatments. This approach helps ensure that her patients receive dependable care without unnecessary delays or complications.

The Rising Success of Exxua™

Among the innovations from 2024, Exxua™ (Gepirone) has gained significant traction in 2025. Exxua builds on the success of ketamine and Auvelity by targeting the glutamatergic system, offering a novel mechanism of action for patients with Major Depressive Disorder (MDD). This mechanism allows for potentially faster relief of depressive symptoms compared to traditional SSRIs.

Many clinicians report promising results with Exxua. Dr. Kim shared her optimism, stating, “Exxua is in the same class as a medication called Buspar, which is widely used and indicated mainly for generalized anxiety. It is typically dosed two to three times a day, which can make adherence difficult, so a once-daily medication in a similar class that may better target anxiety is exciting.”

Dr. Kim also highlighted Exxua’s minimal sexual side effects, which address a common barrier to adherence with many antidepressants. While Exxua’s potential is promising, Dr. Kim noted that logistical challenges, such as cost and insurance coverage, will likely delay widespread use. “Logistically, these medications will not likely be commonly used until patents expire and costs come down, so these medications will unlikely change my practice anytime soon,” she added.

Zuranolone: A Breakthrough for Postpartum Depression

In 2025, Zuranolone (Zurzuvae) is emerging as a key player in depression treatment, particularly for postpartum depression. Approved in 2024, Zurzuvae represents a breakthrough as the first oral medication specifically designed for postpartum depression, targeting neurosteroids to regulate hormonal imbalances. Dr. Kim shared her optimism about its practicality, noting that the oral formulation addresses significant barriers that limited the use of its predecessor, Zulresso, an intravenous treatment which was discontinued in 2025.

Looking ahead, clinicians are keeping an eye on promising treatments that can emerge in 2025. Ujjwal Ramtekkar, MD, MBA, CPE, MPE, DFAACAP, FAPA, who serves as Chief Medical Officer at LifeStance, comments that, “Emerging antidepressant medications like Aticaprant—which is pending FDA approval—target novel biological pathways, unlike the traditional serotonin and norepinephrine targets. These treatments could be beneficial for individuals who have not responded to traditional first-line medications for depression. These types of treatments may have the potential to drive a more personalized approach to mental health care, moving beyond one-size-fits all medications to deliver faster relief and renewed hope for those who have not responded to traditional treatments.”

Everyone’s experience with depression is unique, and effective treatment must reflect that individuality. As part of our commitment to deliver personalized, evidence-based care, LifeStance clinicians carefully consider the symptoms that are most impairing to the individual and the most suitable medication to address them.

-Ujjwal Ramtekkar, MD, MBA, CPE, MPE, DFAACAP, FAPA

Major Depressive Disorder (MDD) is one of the most common mental health conditions, affecting 21 million adults in the United States, or 8.3% of the population. Staying on top of the latest advancements in depression treatment is important to LifeStance, one of the largest outpatient mental and behavioral healthcare providers in the country.

In particular, Dr. Ramtekkar underscores that, “Everyone’s experience with depression is unique, and treatment plans should recognize that. As part of our commitment to deliver personalized, evidence-based care, LifeStance clinicians carefully consider the symptoms that are most impairing to the individual and work to identify the most suitable medication to address them.”

This approach often helps patients receive more appropriate and effective treatments for their unique needs.

References

  1. Drug Trials Snapshots: Exxua (January 10, 2025). U.S. Food & Drug Administration. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-exxua

  2. FDA Approves First Oral Treatment for Postpartum Depression (August 4, 2023). U.S. Food & Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

  3. Major Depression (July 2023). National Institute of Mental Health (NIH). https://www.nimh.nih.gov/health/statistics/major-depression

Authored By 

LifeStance Health

LifeStance is a mental healthcare company focused on providing evidence-based, medically driven treatment services for children, adolescents, and adults.

Authored By Ujjwal Ramtekkar
Ujjwal Ramtekkar

Dr. Ujjwal Ramtekkar is a double board-certified pediatric and adult psychiatrist. He is also an accomplished physician executive and established thought leader in care model innovation, with extensive experience leading diverse clinical teams and integrating a continuum of care to drive clinical outcomes in academic, community practice and managed care settings.


Contributed By

Dr. Stephon Martin, MD

Dr. Stephon Martin, a psychiatrist practicing in Massachusetts, is dedicated to helping individuals across various age groups achieve improved mental health and well-being. He provides compassionate, individualized care to children, adolescents, adults, and seniors, specializing in the treatment of ADHD, anxiety disorders, and mood disorders such as depression and bipolar disorder. Dr. Martin is skilled in offering both medication management and individual therapy, ensuring that his patients receive comprehensive, evidence-based treatment tailored to their specific needs. He is committed to fostering a supportive therapeutic environment where his patients can work toward lasting emotional balance and overall wellness.

Dr. Martin has a particular passion for helping individuals navigate complex life transitions and emotional challenges, with a focus on treating anxiety, depression, and trauma-related disorders such as PTSD. He also works extensively with patients experiencing alcohol and drug use issues, guiding them through their recovery journeys with care and expertise. In addition, Dr. Martin has considerable experience supporting individuals facing reproductive challenges, gender identity issues, and post-partum depression or anxiety. His approach is rooted in empathy and a deep understanding of the nuanced ways these issues impact daily life, offering personalized strategies for healing and growth. Beyond his focus on individual psychiatric care, Dr. Martin is deeply committed to serving specific populations, including military veterans, first responders, and LGBTQ+ individuals.

He understands the unique mental health concerns faced by these communities and works collaboratively to provide specialized support that addresses their distinct challenges. His expertise extends to helping patients manage grief, sleep disorders, and medical conditions that affect mental health, offering a holistic approach to care. Outside of his clinical practice, Dr. Martin is an advocate for social justice reform, reflecting his belief in the importance of equity and community support in mental health care. He enjoys staying active at his local gym and spending time with his French bulldog, often found enjoying the local parks. Dr. Martin proudly serves the Massachusetts community, continuing to provide exceptional psychiatric care to those seeking healing and positive mental health outcomes.

Areum Kim, MD

Dr. Kim is a member of the American Association of Child and Adolescent Psychiatry, the American Psychiatric Association, and the American Medical Association. She specializes in the medication management of pediatric and young adult populations for mood and anxiety disorders, attention deficit disorders, disruptive behaviors, trauma, and obsessive-compulsive disorders (OCD).

Nicholas Cunningham, MSN,PMHNP

A Board Certified Psychiatric Mental Health Nurse Practitioner, Nicholas has 10+ years of experience working in both the intensive care and the psychiatric emergency care settings. Shifting his career to focus more on medication management in the Matthews, NC area, Nicholas brings with him a vast understanding of what is needed to keep his patients active in their lives and helping ensure that the health of the patient matches their perspectives. Nicholas prides himself on the patient-provider connection and wants his patients to understand that he is a partner in their care and that the lines of communication are always open.

In addition to having his Master s in Nursing, Nicholas has also studied at the University of Maryland, where he earned his Baccalaureate of Arts in Communications and has used that knowledge to help aid change in nursing practices at one of the leading local hospitals. In his spare time, Nicholas is active in his community, volunteering at varying non-profits. He has 3 children and a very loving wife. He enjoys being outdoors, playing music and playing disc golf He is an avid reader and believes that life should always be approached from a holistic perspective.