You’ve tried two antidepressants. Then three. Maybe four. Each time, the same pattern – initial hope, weeks of waiting, and disappointing results. Your doctor suggests another medication change, but you’re exhausted from the cycle. You wonder if anything will ever work.
I’ve seen this frustration in patients who arrive at Washington Behavioral Medicine Associates after years of ineffective treatment. Treatment-resistant depression doesn’t mean you’re failing – it means your depression requires a different approach. That’s where ketamine therapy, specifically Spravato (esketamine), changes the treatment path entirely.
Spravato works differently from traditional antidepressants. Instead of targeting serotonin or norepinephrine over weeks, it acts on the glutamate system and can reduce depression symptoms in as little as 24 hours. As of January 2025, Spravato became the first and only FDA-approved monotherapy for treatment-resistant depression, meaning some patients can benefit without needing daily oral antidepressants. At WBMA, we’ve integrated Spravato into our treatment offerings because we’ve seen how it provides relief when other options haven’t.
Here’s what makes ketamine therapy different, who benefits most from Spravato treatment, and what to expect if this approach might work for you.
What Makes Spravato Different From Traditional Antidepressants
Traditional antidepressants – SSRIs like fluoxetine or sertraline, SNRIs like venlafaxine – work by increasing serotonin or norepinephrine levels in the brain. These medications take 4-8 weeks to show effects, and they don’t work for everyone. About one-third of adults with major depressive disorder don’t respond adequately to at least two different oral antidepressants. That’s treatment-resistant depression, affecting approximately 7 million adults in the United States.
Spravato (esketamine) operates through an entirely different mechanism. It’s a non-competitive antagonist of the NMDA receptor, which means it blocks certain glutamate receptors in the brain. Glutamate is the most abundant excitatory neurotransmitter in your nervous system, playing crucial roles in learning, memory, and neural plasticity.
The exact mechanism by which esketamine produces antidepressant effects remains under investigation, but research suggests it promotes rapid synaptogenesis – the formation of new neural connections. Traditional antidepressants slowly adjust neurotransmitter levels; Spravato appears to help the brain create new pathways around the circuits affected by depression.
This difference in mechanism translates to differences in results. While SSRIs require weeks of daily pills before you notice improvement, Spravato can reduce depressive symptoms within 24 hours for some patients. In clinical trials supporting the January 2025 FDA approval of Spravato as monotherapy, patients experienced improvements as early as 24 hours that were sustained through 28 days of treatment.
Who Benefits From Spravato Treatment
Spravato isn’t a first-line depression treatment. The FDA approves it specifically for adults with major depressive disorder who have had inadequate response to at least two oral antidepressants. This is treatment-resistant depression.
You might be a candidate for Spravato if you’ve tried multiple antidepressants without adequate symptom relief, can’t tolerate side effects of oral antidepressants, need faster symptom improvement than traditional medications provide, or experience depression symptoms that significantly impair your daily functioning despite current treatment.
Spravato is also FDA-approved in conjunction with an oral antidepressant for treating depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior. This application addresses the critical need for rapid symptom relief in psychiatric emergencies.
However, Spravato isn’t appropriate for everyone. It requires careful patient selection and medical supervision. You wouldn’t be a candidate if you have hypersensitivity to esketamine or ketamine, certain cardiovascular conditions that make blood pressure increases risky, or a history of substance use disorder involving stimulants or hallucinogens without adequate recovery support.
At WBMA, we conduct thorough evaluation before recommending Spravato. This includes reviewing your complete medication history, assessing your current depression severity, evaluating your cardiovascular health, and discussing your treatment goals and ability to commit to the required monitoring protocol.
The Benefits of Spravato for Treatment-Resistant Depression
Rapid Symptom Improvement
The most significant benefit of Spravato is speed. Depression steals weeks, months, sometimes years from people’s lives. Traditional antidepressants require 4-8 weeks before you know if they’re working. Spravato can begin reducing symptoms within hours to days.
In the clinical trial that led to the 2025 monotherapy approval, patients taking Spravato showed improvements in Montgomery-Asberg Depression Rating Scale scores as early as 24 hours after their first dose, with sustained improvement through 28 days. While individual responses vary, many patients report noticing changes much faster than with oral medications.
This rapid onset matters enormously when depression is interfering with your ability to work, maintain relationships, or function daily. The weeks you would spend waiting for an SSRI to work are weeks you get back.
Different Mechanism When Others Haven’t Worked
If you’ve tried multiple SSRIs or SNRIs without success, your brain’s depression likely doesn’t respond to serotonin-based interventions. Continuing to try different medications in the same class rarely produces better results. Spravato offers a genuinely different approach through the glutamate system.
Research shows that over 140,000 patients worldwide have received Spravato treatment since its initial approval. The drug is now approved in 77 countries. This extensive real-world evidence supports what clinical trials demonstrated – for many people with treatment-resistant depression, glutamate-targeting therapy provides relief when serotonin-targeting medications don’t.
Flexibility in Treatment Approach
The January 2025 FDA approval expanded how Spravato can be used. Previously, patients had to take Spravato in conjunction with an oral antidepressant. Now, Spravato can be prescribed as monotherapy for treatment-resistant depression.
This flexibility benefits patients who experience intolerable side effects from oral antidepressants or have medical conditions that make certain oral antidepressants risky. It also simplifies treatment for patients who can achieve symptom control with Spravato alone, eliminating the need for daily medication management.
Sustained Response with Maintenance Treatment
Spravato treatment follows an induction phase where you receive more frequent doses, followed by a maintenance phase with less frequent administration. Research demonstrates that patients who respond to Spravato during induction and continue maintenance treatment experience sustained symptom improvement and reduced time to relapse compared to discontinuing treatment.
This means Spravato doesn’t just provide short-term relief – it can be part of a long-term management strategy for treatment-resistant depression.
What to Expect During Spravato Treatment at WBMA
Spravato treatment differs significantly from taking a daily pill. Because of potential side effects and safety considerations, esketamine is available only through the Spravato Risk Evaluation and Mitigation Strategy (REMS) program in certified healthcare settings.
Treatment Administration
Spravato comes as a nasal spray. Each device delivers 28 mg of esketamine. Depending on your prescribed dose (56 mg or 84 mg), you’ll use two or three devices with a five-minute rest between each device.
You self-administer the nasal spray under medical supervision at our clinic. A healthcare provider guides you through proper administration technique and monitors you throughout the process.
Monitoring Requirements
After each dose, you’ll remain at the clinic under observation for at least two hours. This monitoring is required because Spravato can cause sedation, dissociation, and temporary blood pressure increases.
During the monitoring period, we check your blood pressure at 40 minutes and 90 minutes post-dose. We also assess for adverse effects, including dissociation (feeling detached from yourself or your surroundings), dizziness, nausea, or increased anxiety.
Most patients tolerate Spravato well, and these effects typically resolve during the two-hour monitoring period. You cannot drive yourself home after treatment – you’ll need to arrange transportation.
Treatment Schedule
Spravato treatment follows a structured protocol:
- Induction Phase (Weeks 1-4): You’ll receive treatment twice weekly. This intensive initial phase establishes therapeutic response.
- Maintenance Phase (Week 5 onward): Treatment frequency decreases to once weekly, then may decrease further to once every two weeks depending on your response and symptoms.
The exact schedule is individualized based on how you respond, side effect tolerance, and depression severity. Some patients achieve remission with less frequent dosing; others need more consistent treatment for optimal symptom control.
Side Effects and Management
Common side effects of Spravato include dissociation, dizziness, nausea, sedation, and temporary blood pressure elevation. In clinical trials, 48-61% of patients experienced some degree of sedation.
These effects are typically most prominent in the first hour after dosing and resolve within the two-hour observation period. As treatment continues, many patients find side effects decrease in intensity.
We manage side effects through dose adjustments when needed, ensuring adequate monitoring, providing a calm, comfortable environment during treatment, and preparing you for what to expect so symptoms don’t cause alarm.
Because Spravato is a Schedule III controlled substance with potential for misuse, treatment occurs only in certified clinics under the REMS program. This oversight protects patient safety while providing access to beneficial treatment.
Ketamine Therapy Research for Other Mental Health Conditions
While Spravato is FDA-approved specifically for treatment-resistant depression and acute suicidal ideation in major depressive disorder, research continues on ketamine therapy for other psychiatric conditions. It’s important to distinguish between FDA-approved uses and research applications.
PTSD Research
Studies have investigated intravenous ketamine for post-traumatic stress disorder, particularly when combined with trauma-focused psychotherapy. Research from the University of Florida published in 2025 found that patients receiving ketamine therapy reported improvements in PTSD symptoms, depression, anxiety, and sleep quality.
The proposed mechanism involves ketamine creating a controlled dissociative state that may help patients process trauma without reexperiencing fear. Some studies have combined ketamine with prolonged exposure therapy or other trauma interventions.
However, ketamine is not FDA-approved for PTSD treatment. These applications remain experimental, and results have been mixed – some studies show benefit while others, particularly in veteran populations, have shown less consistent results.
Anxiety Disorder Research
Limited research has explored ketamine for anxiety disorders, including generalized anxiety disorder and social anxiety disorder. Some studies report rapid reduction in anxiety symptoms, but research remains preliminary.
Ketamine’s dissociative effects create theoretical concerns about worsening anxiety in some patients, so this application requires careful study. Currently, no ketamine formulation is FDA-approved for anxiety disorders.
At WBMA, we focus on evidence-based, FDA-approved applications of treatments. While we stay informed about emerging research, we recommend Spravato specifically for its approved indication: treatment-resistant depression in adults who have not responded to at least two oral antidepressants.
How Spravato Fits Into Your Complete Treatment Plan
Ketamine therapy through Spravato isn’t a standalone solution – it works best as part of an integrated treatment approach. At WBMA, we combine Spravato with other evidence-based interventions tailored to your needs.
Your treatment plan might include Spravato for rapid symptom reduction, individual therapy to address thought patterns and coping skills, medication management if you’re taking oral antidepressants alongside Spravato, and lifestyle interventions including sleep, exercise, and stress management.
For some patients, Spravato provides the symptom relief needed to engage effectively in therapy. Depression’s cognitive effects – difficulty concentrating, negative thinking, low energy – can make therapy less effective. When Spravato reduces these symptoms quickly, therapy often becomes more productive.
We also coordinate with your other healthcare providers. If you’re working with a primary care physician, therapist outside our practice, or specialists for other health conditions, we maintain communication to track your full treatment picture.
Insurance Coverage and Treatment Access
Spravato treatment involves costs for the medication itself, administration and monitoring time at the clinic, and any concurrent oral antidepressants if prescribed. Many insurance plans cover Spravato for FDA-approved indications, though coverage details vary by plan.
We verify insurance coverage before beginning treatment and provide information about out-of-pocket costs. The manufacturer offers patient assistance programs for eligible individuals. Treatment cost should never prevent access to potentially life-changing therapy.
The two-hour monitoring requirement does create a time commitment. You’ll need to arrange transportation after each session and set aside approximately three hours for each treatment visit. During the induction phase with twice-weekly sessions, this represents a significant schedule adjustment.
However, many patients find this investment worthwhile when Spravato provides symptom relief they haven’t achieved with other treatments. We work with you to schedule sessions at times that minimize disruption to work and other commitments.
Schedule Your Spravato Consultation in Chevy Chase, MD
If you’ve struggled with depression that hasn’t responded to multiple antidepressants, ketamine therapy through Spravato may offer the breakthrough you need. Treatment-resistant depression is frustrating and exhausting, but it doesn’t mean you’re out of options.
At Washington Behavioral Medicine Associates, our team specializes in advanced treatment approaches for difficult-to-treat depression. We’re certified to provide Spravato treatment and have the psychiatric expertise to determine if it’s appropriate for your situation.
Your first step is a thorough evaluation where we review your depression history, previous treatments, current symptoms, and overall health. We’ll explain exactly how Spravato treatment works, what the process involves, and whether it aligns with your treatment goals. This consultation involves no obligation – it’s an opportunity to understand your options and make an informed decision.
Depression has already taken enough from your life. Rapid-acting treatments like Spravato can return weeks and months to you that would otherwise be lost waiting for traditional medications to work. Contact our Chevy Chase office to schedule a Spravato consultation and learn whether ketamine therapy might be the treatment approach you’ve been searching for.
