If talk therapy, medication, and lifestyle changes aren’t making a significant difference in your depression symptoms, you still have more options. For those with hard-to-treat depression, one of the most effective approaches could be using Spravato®. It works differently from traditional medications, often helping people feel better within hours or days rather than weeks.1
What Is Spravato®?
Spravato®, a form of esketamine, is a prescription nasal spray that has been approved by the FDA for difficult-to-treat depression. Spravato® works differently than traditional antidepressants, which often target serotonin in the brain. Instead, Spravato® targets glutamate, a chemical that is thought to play a role in depression. By targeting this different chemical pathway, Spravato® can help those who have not found relief from traditional antidepressant medications.
This medication is also beneficial for those who require immediate relief from severe depressive symptoms. As always, your psychiatric provider will assess the potential risks and benefits to determine whether Spravato® is the best course of treatment for you.
Is Spravato® the Same as Ketamine?
Spravato® is a form of ketamine called esketamine. While they work similarly, ketamine and esketamine are enantiomers: they have the same chemical makeup, but the components are arranged differently. This makes esketamine more selective in how it acts on NDMA receptors in the brain, thought to make it a more potent antidepressant.
Additionally, the ways that ketamine and Spravato® are administered are different: Ketamine is typically given in an IV, while Spravato® is a nasal spray.
Why Some Depression Is Harder to Treat
Depression is complex. For about one in three adults, standard antidepressants that target serotonin and norepinephrine do not provide enough relief. These medications adjust the brain’s ability to create and process serotonin and norepinephrine, which can improve mood over time.2
But for some people, these medications aren’t enough to make a big difference in mood. This is called difficult-to-treat depression, meaning symptoms continue even after trying at least two antidepressants at the right dose and duration.2 Others have a difficult time tolerating these antidepressants long-term due to unwanted side effects.
How Does Spravato® Work for Depression?
Spravato® contains esketamine, a form of ketamine that is taken as a nasal spray under medical supervision. Instead of focusing on serotonin or norepinephrine like typical antidepressants, Spravato® targets the NMDA (N-methyl-D-aspartate) receptor in the brain, rapidly increasing glutamate levels. This cascade effect ultimately helps form new neural connections, improving mood and cognitive function.3
The Role of Glutamate in the Brain
Think of glutamate as the “messenger” that helps brain cells stay in touch. It keeps different parts of the brain connected, especially those involved in mood, memory, and motivation. When these signals weaken, depression can make the brain feel like it is stuck in slow motion.
Spravato® helps get that communication moving again. Many people describe it as if their brain has been rebooted after being frozen for a long time.
How Spravato® Helps the Brain Reconnect
Traditional antidepressants often take four to six weeks to work because they gradually adjust brain chemistry over time, but Spravato® takes a different route. By acting directly on glutamate receptors, it helps restore communication in the brain more quickly. Many clients begin to notice small but meaningful shifts, such as more energy, clearer thinking, or renewed interest in daily life, after just a few treatments.3
Spravato® works by:
- Upping glutamate activity, which wakes up areas of the brain that have been quiet during depression.
- Encouraging new brain connections, helping clients feel more flexible and emotionally responsive.
- Supporting long-term brain health through better communication between mood-regulating regions.
Benefits of Spravato® for Hard-to-Treat Depression
If you’ve tried other medications for depression and not found relief, Spravato® could hold several benefits. One of the main ones is how quickly it starts working, with many people seeing improvements in depression symptoms in about a day. People who have been in depression treatment for years might be surprised at how they’re able to find new insights and utilize their coping skills more effectively, thanks to the neuroplasticity effect of Spravato®.
Just a few of the benefits of Spravato® treatment include:
- Rapid relief: Many people start to see improvement in their depressive symptoms after just one or two sessions.
- Improved overall functioning: With continued treatment, individuals may experience an improvement in their overall well-being and ability to perform daily activities.
- Enhanced efficacy when combined with another antidepressant: Spravato® is often combined with another oral antidepressant, boosting the effectiveness of both medications.
- New insights in therapy: Thanks to the boost in neuroplasticity, many people on Spravato® find they are more able to better utilize their coping mechanisms, process emotions more efficiently, and make more progress in therapy.
- Convenience and accessibility: Many people prefer Spravato® to ketamine because the self-administered nasal spray is less invasive and uncomfortable compared to IV ketamine treatments.
What to Expect During Spravato® Treatment
Spravato® is given only in certified healthcare settings as part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program. At Northeast Health Services, sessions take place in a calm and supportive environment designed to help clients feel comfortable and cared for throughout the process.
Each Spravato® appointment includes:
- Self-administration of the nasal spray with guidance from a healthcare provider
- Observation and monitoring for at least two hours, including regular check-ins and blood pressure readings
- Recovery time, where clients rest quietly, listen to music, or read
- Post-treatment care, since driving or operating machinery is not allowed until the next day after restful sleep
We also encourage our Spravato® clients to attend talk therapy sessions with a trained therapist. This combination of medication and therapy has been shown to be highly effective in treating depression.
Typical Spravato® Treatment Schedule
Here’s the typical timeline for Spravato® treatment, though this will vary from person to person:
- Weeks 1–4: Two treatments per week during the induction phase
- Weeks 5–8: One treatment per week
- Ongoing: Weekly or every other week, depending on how you feel and respond
How Long Will It Take to Feel Better After Starting Spravato® Treatments?
Some people will notice a lift in mood within a day or so of their first treatment. For others, changes build steadily over the first few weeks. Clients who continue treatment often find that their symptoms stay more stable and are less likely to return.3
The timing is different for everyone. There is no single pattern, but many people describe feeling lighter or more themselves again after years of feeling weighed down.
Possible Side Effects of Spravato®
Spravato® can cause temporary side effects such as dizziness, nausea, feeling detached from one’s surroundings (dissociation), or sleepiness. These effects usually appear soon after taking the medication and fade the same day.3 Plus, side effects are most likely at someone’s first appointment, when anticipatory anxiety is higher, and typically lessen each visit.4
Less common effects may include:3
- Mild increases in blood pressure
- Brief changes in perception or sensation
- Headache or fatigue after treatment
Because of these possibilities, all clients stay in the treatment space for at least two hours. Every session is guided by experienced professionals who are there to monitor your comfort and well-being.
How Much Does Spravato® Cost?
At our clinics all over Massachusetts, we do our best to work with your insurance company to get the cost of Spravato® treatments as low as possible for you. If you qualify for Spravato®, you’ve already received a depression diagnosis and tried at least a couple other medications, so your insurance company should see the benefits of covering Spravato® as part of your care.
Northeast Health Services is in-network with most insurance companies, including Medicare and Medicaid. Our intake team will work with your insurance company and help you navigate your payment options.
Get Started With Spravato® at Northeast Health Services
At Northeast Health Services, we understand that every person’s journey with depression is unique. That’s why we offer individualized treatment plans to help our clients find relief and improve their quality of life. Call 508.794.8711 or fill out a quick intake form to get in touch with Northeast Health Services and start your healing journey.
Frequently Asked Questions
What is the success rate of Spravato® treatment?
Spravato® has been proven to be effective for hard-to-treat depression, with studies showing around a 70% success rate in lowering depression symptoms.5 Additionally, remission rates are usually lower than with other forms of depression treatments, between 30-58%.4
What to avoid while using Spravato®?
Certain medications can interact with Spravato®, such as certain depressants, stimulants, and MAOI medicines. Be sure to tell your healthcare provider about all medications you’re on, including supplements, before starting Spravato® treatment. Additionally, some people may experience nausea after taking Spravato®, so it’s recommended that you avoid eating two hours before, and drinking 30 minutes before.6
How long do most people stay on Spravato®?
Typical Spravato® treatment involves two sessions per week for the first month or so, then weekly visits for the next month, with ongoing care after that involving weekly or biweekly sessions. The length of time someone will continue with their Spravato® treatments will depend on a variety of factors, but many clients stay on this regimen long-term.7
Can Spravato® be covered by insurance?
Yes, Spravato® may be covered by insurance if you have behavioral health insurance coverage on your plan. Be sure to check with the clinic in your area to see if their care is in-network with your insurance plan.
Footnotes:
- https://www.spravato.com/files/patient-discussion-guide.pdf
- https://www.spravato.com/spravato-right-me/
- https://www.spravato.com/files/SPRAVATO-Patient-Brochure.pdf
- Maxwell Z. Price, Richard L. Price. (2024). Benefits and risks of esketamine nasal spray continuation in treatment-resistant depression. Biomarkers in Neuropsychiatry, 11. https://doi.org/10.1016/j.bionps.2024.100104
- Wang, K., Eftang, C. N., Jakobsen, R. B., & Årøen, A. (2020). Review of response rates over time in registry-based studies using patient-reported outcome measures. BMJ open, 10(8). https://doi.org/10.1136/bmjopen-2019-030808
- https://www.spravato.com/patient-education/
- https://www.spravato.com/taking-spravato/