By the clinical team at Next Step Psychiatry • Lilburn, GA
In 2025, the FDA granted a significant new approval for Spravato (esketamine nasal spray): it can now be used as monotherapy for treatment-resistant depression. This represents a major shift in how psychiatrists treat severe depression. At Next Step Psychiatry in Lilburn, we’re excited about this development and what it means for our patients struggling with major depressive disorder that hasn’t responded to traditional antidepressants.
What This Approval Means
Previously, Spravato was only approved for use in combination with an oral antidepressant. Patients needed to be on both Spravato and another medication like an SSRI or SNRI. The new monotherapy approval means Spravato can now be the sole psychiatric medication for some patients with treatment-resistant depression. This is significant because it simplifies treatment, reduces polypharmacy (taking multiple medications), and opens Spravato to patients who’ve struggled with side effects from other antidepressants.
The approval was based on compelling clinical trial data showing that Spravato monotherapy significantly reduces depressive symptoms and is well-tolerated. This represents validation of what many psychiatrists have observed clinically—that Spravato’s unique mechanism of action makes it powerful enough to work alone in appropriately selected patients.
Who Is a Good Candidate for Spravato Monotherapy?
Not every patient with depression will benefit from Spravato monotherapy. The ideal candidate has:
- Major depressive disorder that hasn’t responded to at least two adequate antidepressant trials
- Severe symptoms causing significant functional impairment
- No active substance use disorder (Spravato has abuse potential)
- Willingness to attend twice-weekly dosing sessions initially
- Ability to be monitored during and after sessions (two hours post-dose)
- Tolerance of dissociative effects during the treatment window
Patients who had trouble tolerating the side effects of traditional antidepressants are often excellent candidates for Spravato monotherapy. Since they don’t need a concurrent oral antidepressant, there’s less opportunity for drug interactions and side effect accumulation.
How Spravato Monotherapy Works
Spravato is administered as a nasal spray in our clinical office, typically twice weekly during the initial two-week induction phase, then weekly for the continuation phase. The nasal mucosa rapidly absorbs esketamine into the bloodstream. Within minutes, patients feel a dissociative effect—a sense of detachment or floating sensation. Most describe this as tolerable and actually report it helps them disengage from their depressive thoughts.
The dissociative effects peak around 20 minutes and resolve within an hour. Patients rest in our clinic for two hours post-administration while we monitor their vital signs and recovery. During this time, many patients relax or sleep. The antidepressant effects develop more gradually—many patients report noticing mood improvement within days to weeks, though full benefits may take weeks to manifest.
Benefits Specific to Monotherapy
Using Spravato without a concurrent oral antidepressant offers several advantages. First, fewer medications mean simpler medication management and less cognitive load during depression when thinking is already foggy. Second, avoiding traditional antidepressant side effects is meaningful—no sexual dysfunction, no weight gain, no emotional blunting. Third, the rapid-onset antidepressant effect often provides hope and motivation as patients begin to feel better within days rather than waiting weeks for traditional antidepressants to work.
Limitations and Considerations
Spravato monotherapy isn’t for everyone. The requirement for in-office administration twice weekly is a significant commitment. It requires reliable transportation to Lilburn or nearby Atlanta-area clinics twice per week initially. The cost and insurance coverage questions remain important considerations. Additionally, maintenance of benefits typically requires ongoing dosing—this isn’t a cure that resolves depression permanently.
Integration Into Treatment at Next Step Psychiatry
At Next Step Psychiatry, we’re integrating Spravato monotherapy into a comprehensive approach to treatment-resistant depression. We thoroughly evaluate each patient, discuss the risks and benefits, and ensure they understand what to expect. We monitor symptoms closely, adjust dosing protocols based on individual response, and provide psychoeducation about what they’ll experience. Many of our patients receiving Spravato also benefit from concurrent psychotherapy to develop coping strategies and process underlying issues contributing to depression.
The Future of Depression Treatment
The FDA approval of Spravato monotherapy represents the field of psychiatry moving toward more personalized, mechanism-based treatment. Rather than just trying different SSRIs or SNRIs, we now have the option to use a medication with a completely different mechanism when standard approaches haven’t worked. For patients in Lilburn, Atlanta, and Gwinnett County, this represents hope and new options for severe, treatment-resistant depression.
Call 678-437-1659 to discuss whether Spravato monotherapy might be right for you.
This article is for informational purposes only and is not a substitute for professional medical advice. If you or someone you know is in crisis, call 911 or the 988 Suicide & Crisis Lifeline.