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If you have lived with treatment-resistant depression, you may be exhausted from trying one treatment after another without feeling like yourself again. You may have followed medication plans, attended therapy, and waited patiently for improvement: only to remain stuck in the same heavy fog.
That experience can be deeply discouraging. But needing another treatment does not mean you have failed, and it does not mean recovery is out of reach. Spravato treatment, also called esketamine therapy, is one evidence-based option that may help some adults with treatment-resistant depression experience meaningful improvement.
At Light-tunnel Behavioral Health Services Inc. in New Haven, our psychiatric providers create individualized plans based on your symptoms, medical history, previous treatments, and goals. Dr. Omolola Aragbada, PMHNP, is one of the psychiatric providers on our team. The purpose of this guide is to help you understand what a typical Spravato treatment journey may look like before you schedule an evaluation.
What Is Spravato and How Does It Work?
Spravato is the brand name for esketamine, a prescription nasal spray used in adults with treatment-resistant depression. It works differently from many traditional antidepressants.
Many standard antidepressants primarily influence monoamine neurotransmitters such as serotonin, norepinephrine, and dopamine. Esketamine primarily acts on the brain’s glutamate system by blocking NMDA receptors. This can increase downstream AMPA-related signaling and support processes associated with synaptic plasticity, including the growth and strengthening of connections between neurons.
An accessible way to picture this is to imagine your brain as a communication network. Depression can make important roads underused, damaged, or blocked. Esketamine may help open alternate routes and encourage the brain to build stronger “highways” between nerve cells. These changes may support more flexible thinking, emotional regulation, and responsiveness to other forms of care.
The exact antidepressant mechanism is still being studied, and not every person responds. Spravato is not a guaranteed cure. However, its glutamatergic action helps explain why esketamine treatment may work more quickly than some conventional depression treatment options.
Step 1: Your Initial Psychiatric Evaluation
Before treatment begins, you will complete a detailed psychiatric evaluation. This may be scheduled as an in-person appointment or, when clinically appropriate and available, a telehealth appointment for an initial discussion. Spravato dosing itself must occur in a certified healthcare setting under direct clinical supervision.
During the evaluation, your provider may review:
- Your current depressive symptoms and functional difficulties
- Previous antidepressant trials, including dose and duration
- Current medications and supplements
- Medical conditions, blood pressure, and cardiovascular history
- History of mania, psychosis, substance use, or medication misuse
- Suicidal thoughts, safety concerns, and available supports
- Pregnancy or breastfeeding considerations
- Insurance requirements and treatment logistics
Spravato is often considered when an adult has not received adequate benefit from at least two antidepressant treatments given at appropriate doses and durations. Your provider will determine whether it is clinically appropriate: not simply whether you meet one checklist item.
You can learn more about our psychiatric evaluation services and medication management before your consultation.
Step 2: Preparing for Your First Treatment Session
Your provider will give you individualized instructions. Common preparation steps may include:
- Avoiding food for at least two hours before treatment
- Avoiding liquids for at least 30 minutes before treatment
- Taking nasal corticosteroids or decongestants at least one hour before Spravato, if prescribed
- Reviewing all medications that may increase sedation or blood pressure
- Arranging transportation home in advance
- Planning a quiet schedule for the remainder of the day
You should bring a list of your medications and tell your provider about any new symptoms or medication changes. Do not stop an antidepressant, stimulant, benzodiazepine, or any other prescribed medication without medical guidance.
Step 3: Self-Administering the Nasal Spray Under Supervision
Spravato is self-administered by the patient, but only under direct observation from trained healthcare staff. A clinician will explain how to use the nasal spray device and remain available throughout the session.
The medication is delivered in one or more nasal spray devices depending on your prescribed dose. You will usually sit or recline in a quiet treatment area. The goal is to make the experience calm, private, and medically supervised.
You may notice sensations beginning within approximately 20 to 40 minutes. Some people describe feeling detached, lightheaded, sleepy, dizzy, or as if time and space feel temporarily different. These experiences are commonly referred to as dissociation or perceptual changes. They can feel unfamiliar, so tell your clinical team exactly what you are experiencing.
Step 4: At Least Two Hours of Clinical Monitoring
After administration, you will remain at the clinic for observation. The FDA prescribing information requires monitoring for at least two hours, followed by an assessment to determine whether you are clinically stable and ready to leave.
Your care team may monitor:
- Blood pressure and heart rate
- Alertness and sedation
- Breathing and oxygen saturation
- Dissociation or perceptual changes
- Nausea, dizziness, headache, or vertigo
- Anxiety, confusion, or other emotional changes
- Your overall mental status and safety
Blood pressure is commonly reassessed around 40 minutes after dosing because increases may peak around that time. Most short-term effects improve the same day, but the exact experience varies.
Step 5: Leaving Safely After Treatment
You should not drive yourself home after Spravato treatment. Arrange for a trusted adult or approved transportation option to take you home. The prescribing information advises avoiding driving, operating machinery, or other activities requiring complete alertness until the next day following a restful sleep.
After your visit, plan to:
- Rest in a calm environment
- Drink fluids when appropriate
- Avoid important legal, financial, or work decisions
- Follow your provider’s instructions
- Contact the clinic if symptoms feel severe, prolonged, or unusual
Step 6: Understanding the Spravato Treatment Timeline
The standard adult treatment schedule for treatment-resistant depression is generally divided into phases:
Weeks 1–4: Induction
- Spravato is typically administered twice weekly
- Your provider monitors tolerability, blood pressure, dissociation, sedation, and symptom response
- Treatment benefit is formally evaluated at the end of the four-week induction phase
Weeks 5–8: Early Maintenance
- Treatment commonly decreases to once weekly
- Your dose and frequency may be adjusted according to benefit and side effects
Week 9 and Beyond: Individualized Maintenance
- Many patients receive treatment once weekly or every two weeks
- Some people may eventually extend the interval further
- Your provider will aim for the least frequent schedule that maintains benefit
The schedule is not identical for everyone. Missing sessions, changes in symptoms, side effects, insurance requirements, and your overall treatment response may affect the plan.
How Quickly Can Spravato Work?
Some people notice changes after the first few treatments, while others require more time. Early improvement does not always mean full remission, and no initial change does not necessarily mean the treatment will never help.
In a randomized controlled trial of adults with major depressive disorder and imminent suicide risk, Canuso et al. (2018) found significantly greater reductions in depressive symptoms with intranasal esketamine than placebo within the first 24 hours. However, clinician-rated suicidality did not consistently differ from placebo, and Spravato should never be considered a substitute for emergency psychiatric care or hospitalization when needed.
In the phase 3 TRANSFORM-2 trial, Popova et al. (2019) reported a significantly greater reduction in Montgomery–Åsberg Depression Rating Scale scores at day 28 for flexibly dosed esketamine plus a newly initiated oral antidepressant compared with placebo nasal spray plus an oral antidepressant.
Longer-term treatment may also matter. In the randomized withdrawal SUSTAIN-1 trial, Daly et al. (2019) found that continuing esketamine plus an oral antidepressant reduced relapse risk by approximately 51% among stable remitters and approximately 70% among stable responders, compared with discontinuing esketamine.
These results describe groups of study participants: not a guarantee about what will happen for you.
Common Side Effects and What to Report
Common effects may include:
- Dissociation or feeling disconnected
- Dizziness or vertigo
- Sleepiness or sedation
- Nausea or vomiting
- Increased blood pressure
- Headache
- Altered taste or numbness
- Anxiety or feeling “drunk”
- Temporary difficulty concentrating
Tell your clinical team immediately if you experience chest pain, shortness of breath, severe headache, vision changes, seizure-like activity, inability to stay awake, or symptoms that feel medically urgent.
You should also report new urinary urgency, pain with urination, or frequent nighttime urination during longer-term treatment.
What to Do: and What to Avoid
What to do
- Arrange transportation before every session.
- Follow fasting and medication instructions from your provider.
- Continue prescribed antidepressants unless your prescriber tells you otherwise.
- Report every symptom, including emotional or perceptual changes.
- Attend follow-up visits so your treatment plan can be adjusted safely.
- Pair medication treatment with appropriate therapy, healthy routines, and social support when possible.
What to avoid
- Do not drive after treatment or operate machinery until the next day after restful sleep.
- Do not drink alcohol around treatment unless your provider specifically gives different instructions.
- Do not combine Spravato with sedating substances, opioids, or recreational drugs without medical guidance.
- Do not stop psychiatric medication abruptly.
- Do not hide suicidal thoughts, worsening depression, or medication misuse concerns from your care team.
When Should You Discuss Spravato?
Spravato may be worth discussing if you are an adult experiencing significant depression despite adequate trials of standard antidepressants, particularly when symptoms are interfering with work, relationships, sleep, self-care, or safety.
It may not be appropriate for everyone. Your provider must carefully assess conditions such as uncontrolled cardiovascular risk, certain vascular conditions, a history of intracerebral hemorrhage, medication allergies, psychosis, pregnancy, breastfeeding, or substance use concerns.
At Light-tunnel Behavioral Health Services Inc., our New Haven team can help you review whether Spravato belongs in a broader, personalized treatment plan. You can explore our behavioral health services, meet our providers, or schedule an appointment.
Medical Safety Disclaimer and Crisis Resources
This article is for educational purposes only and does not replace an evaluation or treatment plan from a qualified healthcare professional. Spravato is a prescription medication with important risks, contraindications, monitoring requirements, and potential interactions. Only a licensed clinician can determine whether esketamine treatment is appropriate for you.
Spravato is not approved as a stand-alone suicide-prevention treatment, and improvement after a dose does not eliminate the need for hospitalization or emergency care when clinically indicated.
If you may hurt yourself, have a suicide plan, or are experiencing an immediate psychiatric or medical emergency:
- Call or text 988 to reach the Suicide & Crisis Lifeline.
- Call 911 or go to the nearest emergency department.
- Do not remain alone: contact a trusted person who can stay with you.
References
Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. American Journal of Psychiatry. 2018;175(7):620–630. PubMed | doi:10.1176/appi.ajp.2018.17060720
Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. American Journal of Psychiatry. 2019;176(6):428–438. PubMed | doi:10.1176/appi.ajp.2019.19020172
Daly EJ, Trivedi MH, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893–903. PubMed | doi:10.1001/jamapsychiatry.2019.1189
U.S. Food and Drug Administration. SPRAVATO (esketamine) nasal spray prescribing information, revised January 2025.
Next Post in the Series
Read the published Spravato guide: Can Spravato Treatment Really Help You Break Free From Treatment-Resistant Depression?