Depression

Roughly 1 in 3 individuals with major depression do not improve after trying two or more standard antidepressants. For that group, ordinary treatment plans can start to feel like a series of dead ends. Spravato entered the picture as something genuinely different: the first depression medication in decades to act through a separate pathway in the brain than the pills most individuals have already tried, and one of the few with the potential to ease symptoms within hours rather than weeks. Understanding what it is, how it works inside the brain, and what a treatment session looks like can make it easier to judge whether this option is worth raising with a healthcare provider. What Is Spravato? Spravato is the brand name for esketamine, a prescription nasal spray used to treat certain forms of depression in adults. Esketamine is the more potent form of the ketamine molecule, delivered into the nose so it absorbs through the nasal lining and into the bloodstream. Each device delivers 28 mg of medication in two sprays. Because of its effects and its potential for misuse, Spravato is classified as a Schedule III controlled substance and is given only in a certified medical setting, never dispensed for use at home. What Does Spravato Treat? Spravato has two FDA-approved uses, both in adults. The first is treatment-resistant depression, meaning major depressive disorder (MDD) that has not improved after at least two oral antidepressants. For this use, Spravato can be prescribed on its own or alongside an oral antidepressant. The second is depressive symptoms in adults with MDD who are experiencing acute suicidal thoughts or behavior, where it is used together with an oral antidepressant. It's worth being clear about what this second use does, and doesn't, mean. Spravato hasn't been shown to prevent suicide or reduce suicidal thoughts or behavior on its own, and starting treatment doesn't rule out the need for hospitalization if that's what someone's care team decides is necessary, even if symptoms start to improve after the first dose. Outside of those indications, Spravato is not FDA-approved for other conditions. It is not a first-line treatment, and it is not approved for anxiety, even though anxiety and depression often occur together. A provider generally considers it only after other antidepressants have been tried without adequate relief. For the individuals it does fit, it can widen what recovery looks like, and anyone weighing it can talk with a psychiatric provider about whether esketamine therapy aligns with their history, symptoms, and goals. Take Our Quick and Easy Depression Questionnaire Major depressive disorder affects millions of people across all age groups. Take this assessment to identify symptoms commonly associated with depression and understand if you may be suffering from clinical depression. Start Questionnaire Questionnaire Disclaimer Questionnaire Disclaimer × This health survey is provided for informational and educational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider regarding any personal health concerns. Completion of this survey does not establish a patient-clinician relationship. Responses are NOT monitored. If you are thinking of harming yourself or others please call toll-free 9-8-8 for the National Suicide & Crisis Lifeline (available 24/7), 9-1-1 or go to your nearest emergency room. By proceeding, you acknowledge this disclaimer and agree that this tool is for general awareness only. You assume all risks associated with its use. The survey administrators are not liable for reliance on its content. The above health survey is based on the Patient Health Questionnaire PHQ-9. The PHQ-9 and GAD-7 are Pfizer products. PHQ Copyright © 1999 Pfizer Inc. No permission required to reproduce, translate, display or distribute. In the last two (2) weeks, how often have you been bothered by any of the following problems? "*" indicates required fields Step 1 of 10 10% Question 1*Little interest or pleasure in doing things.Not At AllSeveral DaysMore than Half the DaysNearly Everyday Next Question 2* Feeling down, depressed, or hopelessNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 3*Trouble falling asleep, staying asleep, or sleeping too muchNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 4*Feeling tired or having little energyNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 5*Poor appetite or overeatingNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 6*Feeling bad about yourself – or that you are a failure or have let yourself or your family downNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 7*Trouble concentrating on things, such as reading the newspaper or watching televisionNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 8*Moving or speaking so slowly that other people could have noticed. Or, the opposite – being so fidgety or restless that you have been moving around a lot more than usualNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Question 9*Thoughts that you would be better off dead, or of hurting yourself in some wayNot At AllSeveral DaysMore than Half the DaysNearly Everyday Previous Next Your Zip Code*Please enter your zip codeEmail Address*Please enter your email If you feel you are at risk of harming yourself or someone else, call 911 or seek emergency assistance. You may also contact the National Suicide Crisis Lifeline by dialing 988. Previous Get Results How Does Spravato Work? Most antidepressants act gradually on serotonin, norepinephrine, or dopamine. Spravato works on a different chemical messenger altogether. A review of glutamate-targeted antidepressants describes glutamate as the brain's most abundant neurotransmitter and a central player in how neurons build new connections, with measurable differences in glutamate signaling between people with and without depression. Esketamine blocks NMDA receptors, a type of glutamate receptor. That blockade triggers a brief surge of glutamate, which activates a different type of receptors known as AMPA receptors, and sets off a cascade that strengthens and rebuilds synaptic connections in mood-regulating regions of the brain. Many researchers believe this rapid boost to synaptic plasticity is what may allow symptoms to lift faster than they do with traditional medication, although the full mechanism is still not completely understood. Is Spravato the Same as Ketamine? Spravato and ketamine are closely related but not identical. Esketamine is the S-enantiomer, one of the two mirror-image halves, of the ketamine molecule. Both compounds share the same core mechanism as NMDA receptor antagonists, which is part of why their risk profiles overlap. Many people have first heard of Spravato described as a “ketamine nasal spray,” and while that nickname is understandable, it is not quite accurate. The shorthand blurs an important distinction: Spravato is the specific, FDA-approved esketamine formulation, while plain ketamine is an older anesthetic that has never been approved as a nasal spray for depression. The practical differences, though, are large. Spravato is an FDA-approved, standardized nasal spray with a defined dose and a built-in safety program. Ketamine used for depression is typically given off-label as an intravenous infusion or a compounded preparation, sometimes marketed as a compounded ketamine nasal spray, without the same regulatory oversight or dosing standards. For individuals comparing rapid-acting options, it may also help to see how Spravato lines up against TMS, a non-medication approach to stubborn depression. LifeStance Health connects you with clinicians who understand and treat depression. With the right support, brighter days are within reach. Find a provider near you: Arizona California Colorado Delaware Florida Georgia Illinois Indiana Kansas Kentucky Maine Maryland Massachusetts Michigan Minnesota Missouri Nevada New Hampshire New Jersey New York North Carolina Ohio Oklahoma Oregon Pennsylvania Rhode Island South Carolina Tennessee Texas Utah Virginia Washington Wisconsin What to Expect During Spravato Treatment Spravato is always taken in a doctor's office or clinic, never at home. Individuals spray the medication themselves under direct observation and then stay to be monitored. Under the FDA's restricted REMS program, a healthcare provider must watch each individual for at least two hours after every dose, checking for sedation, dissociation, and changes in blood pressure before clearing them to leave. Because the medication can cause drowsiness and a temporary sense of detachment, individuals cannot drive afterward and need to arrange a ride home. A typical course begins with an induction phase of two sessions per week for the first four weeks, then tapers to weekly or every-other-week maintenance sessions based on how a person responds. Because every dose must be given in a REMS-certified setting, access often depends on whether a certified clinic is within reach. With more than 500 locations across the country, LifeStance is well positioned to make Spravato therapy available to individuals in 15 states, with trained providers handling administration and the required two-hour monitoring on site. How Long Does Spravato Take to Work? Spravato is considered a rapid-acting antidepressant, and some people notice a lift in mood within the first day or week rather than the month or more that oral medications often require. Onset varies from person to person, so a provider usually evaluates the response over the first several sessions before settling on a long-term plan. Spravato Side Effects Most side effects are tied to the first couple of hours after a dose and tend to ease before the observation period ends. The most common include: Dissociation: a temporary feeling of being detached from oneself or one's surroundings. Dizziness and vertigo: a spinning or off-balance sensation in the hours after dosing. Sedation: drowsiness that makes driving unsafe until the next day. Nausea: sometimes with vomiting, usually mild and short-lived. Increased blood pressure: a transient rise that staff track throughout the session. The more serious risks are the reason for the in-office monitoring requirement: heavy sedation, significant blood pressure spikes, and, in rare cases, slowed breathing. Like other antidepressants, Spravato carries a boxed warning about an increased risk of suicidal thoughts in some children and young adults, and is not recommended during pregnancy. A provider also screens for conditions, such as certain cardiovascular problems, that can make the medication unsafe. Is Spravato Right for You? Treatment-resistant depression is not the end of the road, and a certified clinic is where that next conversation can start. Find a Spravato treatment center near you. Spravato is prescribed only when clinically appropriate and should be used only under the supervision of a qualified healthcare provider. References Bhavya, Shetty, S., & Sadasivam, B. (2025). A New Era for Esketamine in Managing Treatment-Resistant Depression: A Systematic Review of Its Use From Adjunct to First-Line Therapy. Cureus, 17(9), e91829. https://doi.org/10.7759/cureus.91829 Janssen Pharmaceuticals, Inc. (2020). Spravato (esketamine) nasal spray, CIII [Prescribing information]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211243s003lbl.pdf McIntyre, R. S., & Jain, R. (2024). Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS drugs, 38(11), 869–890. https://doi.org/10.1007/s40263-024-01114-y

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