Major depressive disorder (MDD) affects millions of people each year. Traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) can provide relief for some people. But for others, these medications may take too long to start to work (up to a month in most cases) Or they may not work at all.
Newer treatments such as Auvelity and Spravato® (esketamine) offer faster-acting alternatives for people struggling with depression that hasn’t improved with standard options. Both treatments target different brain pathways than traditional antidepressants and have been shown in clinical trials to help reduce symptoms more quickly.
Understanding how these two treatments compare can help people and their healthcare providers make informed decisions about what may work best for their situation.
Auvelity vs Spravato: How each one works
Both Auvelity and Spravato are approved by the U.S. Food and Drug Administration (FDA) for adults with major depressive disorder. While both work quickly, they do so in very different ways.
Auvelity is a combination of two medications: dextromethorphan and bupropion.
- Dextromethorphan affects glutamate signaling, a system in the brain involved in learning, memory, and mood regulation.
- Bupropion helps slow the breakdown of dextromethorphan, allowing it to stay active in the body longer.
Together, these effects help improve communication between brain cells, which can reduce depressive symptoms.
Spravato (esketamine), by contrast, is a nasal spray version of ketamine. It also acts on the glutamate system, but it works through a specific brain receptor called the NMDA receptor. This action helps restore normal brain activity patterns in regions related to mood and emotion.
Unlike Auvelity, Spravato is given in a clinic under medical supervision because of potential side effects such as dizziness or sedation.
What clinical research shows
Both treatments have been studied in adults with major depressive disorder, including people who haven’t responded to previous medications.
- Auvelity showed improvement in depressive symptoms in as early as one week, faster than most traditional antidepressants.
- Spravato produced improvements for some people within as little as four hours, especially when combined with an oral antidepressant.
In studies comparing outcomes, both medications significantly reduced depression scores on standard rating scales and helped people feel more motivated and engaged in daily activities.
These results led to their FDA approvals (Spravato in 2019 and Auvelity in 2022) as options for adults needing faster-acting relief from major depression.
Treatment-resistant depression
Many people with major depressive disorder experience treatment-resistant depression (TRD.) This means their symptoms haven’t improved after trying at least two different antidepressants.
Both Auvelity and Spravato were developed to address TRD. Research suggests that these medications can offer meaningful relief when other treatments haven’t worked.
In addition to medication, people with TRD often benefit from combination approaches that include psychotherapy, lifestyle changes, and social support. A healthcare provider can help determine the best treatment plan based on medical history, current symptoms, and treatment goals.
Benefits of rapid-acting antidepressants
Traditional antidepressants can take four to six weeks to show results. For people struggling with severe depression or suicidal thoughts, that delay can feel unbearable.
Rapid-acting treatments like Auvelity and Spravato can begin to relieve symptoms much sooner—sometimes within days. That speed can:
- Improve safety and reduce suicidal ideation
- Help patients feel hopeful sooner
- Decrease the risk of hospitalization
- Support faster return to daily routines and responsibilities
These faster results may also improve therapy or other forms of ongoing care, helping people stay consistent with their overall treatment plan.
Potential side effects and risks
Like all medications, both Auvelity and Spravato come with potential side effects. Understanding them helps people know what to expect and when to contact a healthcare provider.
Common side effects of Auvelity may include:
- Dizziness or sleepiness
- Dry mouth
- Headache
- Increased blood pressure
- Restlessness or difficulty sleeping
Because it contains bupropion, Auvelity may not be suitable for people with a history of seizures or certain eating disorders.
Common side effects of Spravato may include:
- Nausea
- Dizziness or dissociation, a sense of disconnection
- Sleepiness or fatigue
- Increased blood pressure
- Anxiety or headache
Spravato must be administered in a certified medical clinic where patients can be monitored for at least two hours after dosing.
Both medications carry a boxed warning for increased risk of suicidal thoughts in young adults, especially during the early stages of treatment. Close monitoring and open communication with providers are essential.
Comparing Auvelity vs Spravato
While both medications offer fast-acting relief for depression, there are key differences to consider.
| Feature | Auvelity | Spravato (Esketamine) |
| Form | Oral tablet (taken at home) | Nasal spray (given in a clinic) |
| Mechanism | Dextromethorphan and bupropion; targets NMDA receptors and glutamate | Esketamine; targets NMDA receptors through glutamate |
| FDA approval | 2022 | 2019 |
| Use | Major depressive disorder (MDD) | Treatment-resistant depression (TRD) and MDD with suicidal ideation |
| Onset of action | About 1–2 weeks | Often within days or even hours |
| Supervision | Self-administered | Self-administered under clinical supervision |
| Common side effects | Dizziness, dry mouth, insomnia, increased blood pressure | Nausea, dissociation, dizziness, fatigue |
| Monitoring | Periodic check-ins | Required in-clinic observation after each dose |
For some people, the convenience of an at-home medication like Auvelity makes it an appealing choice. Others may prefer the supervised environment of Spravato, particularly if they are dealing with more severe or treatment-resistant depression.
Ultimately, the right option depends on medical history, symptom severity, and response to previous treatments.
Considerations before starting treatment
Choosing between Auvelity and Spravato involves a detailed conversation with a healthcare provider. Key considerations include:
- Diagnosis: whether depression is treatment-resistant or includes suicidal symptoms
- Medical history: conditions like high blood pressure, heart disease, or seizure risk
- Convenience and access: ability to attend in-person treatments versus at-home dosing
- Medication interactions: both drugs may interact with other prescriptions or supplements
- Support systems: access to monitoring, transportation, and ongoing therapy
People beginning either treatment should have regular follow-up appointments to track progress and discuss side effects.
The bottom line
When comparing Auvelity vs Spravato, both represent major advances in the treatment of depression, especially for people who haven’t found relief from traditional medications.
- Auvelity offers a convenient, oral, at-home option that targets new brain pathways and works within weeks.
- Spravato provides rapid relief—often within days—under professional supervision.
Both have shown strong results in clinical trials and are considered safe and effective when prescribed and monitored appropriately.
For anyone struggling with depression, these innovations represent real progress in how quickly and effectively treatment can begin to make a difference.
Key takeaways
- Auvelity and Spravato are fast-acting antidepressants approved by the U.S. Food and Drug Administration for major depressive disorder.
- Both target glutamate pathways in the brain, offering alternatives to traditional SSRIs.
- Auvelity is an oral medication, while Spravato is a nasal spray given in a clinic.
- Each treatment has unique benefits and side effects—discuss options thoroughly with a healthcare provider.
- Rapid-acting treatments can provide relief within days to weeks and may improve outcomes for people with treatment-resistant depression.
Looking for Spravato or ketamine treatment near you?
Pacific Mind Health offers Spravato (esketamine) and ketamine therapy for treatment-resistant depression, major depressive disorder, and more. Our experienced clinicians provide compassionate, evidence-based care to help you feel better.
Ready to take the next step? Schedule a free consultation today to see if Spravato or ketamine is right for you.
