Home Brain and Mental Health Esketamine (Spravato) for Depression: What to Expect and Side Effects

Esketamine (Spravato) for Depression: What to Expect and Side Effects

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Depression can feel especially unforgiving when standard treatments have not helped—or have helped only a little, too slowly. Esketamine (brand name Spravato) is one of the few options designed for that exact situation: it is a fast-acting, clinic-administered nasal spray that works through glutamate signaling rather than the serotonin-first approach many people associate with antidepressants. For some patients, that difference matters—because symptom relief can begin within hours to days, not weeks.

Esketamine is not a “take-home” medication, and it is not a casual add-on. Doses are given under supervision, with monitoring afterward, because temporary side effects such as dissociation, sleepiness, and blood pressure increases are common. This guide walks through who it is for, what sessions are like, what benefits are realistic, and how to plan for side effects and safety.

Core Points for First-Time Readers

  • Relief can begin within 24 hours for some people, but the full picture usually emerges over several weeks.
  • Sessions require in-clinic dosing and observation, so logistics (rides, scheduling, time off) matter as much as motivation.
  • Dissociation and sleepiness are expected for many patients, which is why same-day driving is typically off-limits.
  • The best outcomes usually come from treating esketamine as one piece of a broader plan (medication strategy, therapy, sleep, and stress supports).

Table of Contents

What esketamine is and does

Esketamine is a nasal-spray form of a ketamine-derived compound used for certain depressive conditions, particularly when depression has not improved with typical antidepressants. The simplest way to understand it is this: most antidepressants try to reshape mood by gradually changing neurotransmitters like serotonin and norepinephrine. Esketamine targets a different lane—glutamate signaling—and may nudge brain circuits involved in mood, learning, and stress response more quickly.

That “quickly” is why many people hear about esketamine in moments of urgency: long-standing treatment resistance, severe symptoms, or episodes where waiting weeks for an oral medication to build effect feels impossible. While the exact biology is still being refined, the clinical reality is clearer: some patients feel a meaningful shift in mood, rumination, or emotional pain within a day or two of starting. Others notice the first change as slightly better sleep, a little more mental “space,” or less psychic heaviness—signals that the nervous system is becoming less locked in threat-mode.

It also helps to be clear about what esketamine is not. It is not talk therapy, and it is not an instant rewrite of your life circumstances. You can feel lighter and still have the same problems waiting at home. And it is not the same experience as taking a daily pill—because the treatment is episodic, supervised, and time-bound.

Many clinics frame the course in phases:

  • Induction: more frequent sessions to see if you respond and to build early momentum.
  • Maintenance: a steadier rhythm (often weekly to every other week) to keep gains from fading.
  • Reassessment: adjusting dose frequency based on relapse risk, side effects, and functioning.

A useful mindset is to treat esketamine like a bridge: it may create enough symptom relief to make other supports work better—therapy becomes more usable, routines become more doable, and self-care stops feeling like climbing a wall with your hands tied.

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Who Spravato is for and who should avoid it

Esketamine is typically considered when depression is both serious and stubborn. Many programs use it for treatment-resistant depression, commonly meaning you have tried at least two antidepressants at adequate dose and duration in the current episode without meaningful improvement. Some settings also use esketamine as part of intensive care for severe depressive states when symptoms are escalating and clinicians want a faster-acting intervention.

That said, “eligible” is not the same as “ideal candidate.” A careful intake matters because the same properties that make esketamine powerful—rapid brain-state changes and short-term perceptual effects—also create risks for certain people.

Clinicians often look at:

  • Symptom pattern: severe depression with prominent anhedonia, slowed thinking, and heavy rumination can respond well, but results vary.
  • Treatment history: prior medication trials, psychotherapy engagement, and whether other options (like medication augmentation or neuromodulation) have been attempted.
  • Medical stability: esketamine can raise blood pressure temporarily; uncontrolled hypertension or specific vascular risks may be disqualifying or require specialist clearance.
  • Psychiatric complexity: a history of psychosis or uncontrolled mania typically calls for extra caution because altered perception during treatment can be destabilizing.
  • Substance use risk: esketamine is a controlled substance in some countries, and clinics often screen carefully for active substance use disorders or high misuse risk.

People sometimes worry that needing esketamine means they have “failed” other treatments. A healthier frame is that depression is biologically diverse. One person’s depression responds to an SSRI and therapy; another person’s depression is more refractory and needs a different tool. Esketamine is not a moral verdict—it is a treatment strategy.

It is also reasonable to ask: Is this safe for my current life? If you cannot reliably arrange transportation, cannot spend a few hours in clinic per session, or have caregiving or job constraints that make post-treatment downtime impossible, those practical issues can undermine success as much as biology can.

Finally, if you are pregnant, trying to conceive, or breastfeeding, it is especially important to discuss risks and alternatives early. Even when something is medically possible, it might not be the best choice for your stage of life.

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What a session feels like

Most people feel less anxious about esketamine once they know what the appointment actually looks like. While each clinic has its own workflow, the experience is usually predictable and structured.

Before you arrive: clinics often recommend avoiding heavy meals beforehand to reduce nausea risk. You may also be advised to limit fluids shortly before dosing so you are comfortable during observation time. If you have frequent nasal congestion or allergies, ask whether a saline rinse or timing of nasal sprays could help—absorption happens through the nasal lining, so a clear nasal passage can make dosing smoother.

Check-in and baseline vitals: you will typically have your blood pressure and heart rate checked. Many sites do a brief symptom check-in: mood, sleep, suicidal thoughts, and any side effects from the last session. Some clinics also confirm you have a safe ride home.

Dosing: you self-administer the nasal spray under supervision. The dose is delivered using multiple devices, spaced with short rest periods. Staff will coach you on posture and technique—usually gentle sniffs rather than deep inhalations—so the medication stays in the nasal cavity rather than draining immediately into the throat.

The “onset” window: effects commonly start within minutes. People describe a range:

  • feeling floaty or heavy-limbed
  • changes in sound sensitivity
  • time distortion (minutes feel longer)
  • emotional softening (less sharp pain, less urgency)
  • dissociation (feeling detached from body, thoughts, or surroundings)

This can be neutral, pleasant, or unsettling. What helps most is a simple plan: comfortable clothing, an eye mask or hat, headphones if allowed, and a grounding phrase you can repeat if you feel uneasy (for example, “This is temporary and monitored.”).

Observation period: you remain in a supervised space until staff are confident you are medically stable and mentally oriented. Many people feel tired afterward. Some feel calm; others feel emotionally tender. Plan for a low-demand day: avoid major decisions, heated conversations, and intense workouts.

A helpful expectation is that esketamine sessions are not “productive time” in the usual sense. They are closer to a medically supervised reset—followed by recovery time—than a normal appointment you can squeeze between meetings.

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How quickly it works and how long it lasts

Esketamine has a reputation for speed, but response is more nuanced than “one dose fixes everything.” Think in layers: acute effects, early response, and durability.

Acute effects (same day): during and shortly after treatment, some people notice a temporary lift in mental pressure—less crushing sadness, less agitation, or a quieter mind. This can feel dramatic, but it can also be subtle: you realize you are not arguing with yourself as relentlessly. Acute effects are not the same as sustained antidepressant response; they are a signal, not a guarantee.

Early response (first 1–2 weeks): many treatment plans start with more frequent dosing specifically to see whether you are a responder. Early signs can include:

  • slightly easier mornings
  • fewer “spiral” episodes
  • improved sleep continuity
  • less avoidance and more initiation of small tasks
  • reduced intensity of suicidal thinking (even if life still feels hard)

Not every improvement looks like happiness. Often it looks like more flexibility: you can consider options again.

Full response window (2–6 weeks): for many patients, the meaningful assessment comes after several sessions. Some respond quickly; others need time for the nervous system to “learn” the new state. It is also common for progress to be uneven—two steps forward, one step back—especially if stress, trauma triggers, or sleep disruption are still active.

Maintenance and durability: the big question is how long benefits last once you space sessions out. Some people do well moving to weekly or every-other-week dosing. Others need closer spacing, at least during high-stress seasons. If symptoms return when spacing increases, clinics may adjust frequency or revisit the broader plan (medications, therapy focus, substance use, sleep apnea screening, or hormonal factors).

A realistic way to track progress is to measure function, not mood alone:

  • Are you showering and eating more consistently?
  • Are you responding to messages instead of disappearing?
  • Is your thinking less catastrophizing?
  • Are you able to use coping skills when activated?

These are often the first durable wins—because they create momentum that outlasts any single treatment day.

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Side effects and safety monitoring

Side effects are not an afterthought with esketamine—they are part of why the treatment is supervised. The goal is not “no side effects,” but predictable, temporary effects that are managed safely.

Common short-term side effects: many patients experience some combination of:

  • Dissociation: feeling detached from body, thoughts, or surroundings
  • Dizziness or vertigo: unsteady feeling, especially when standing
  • Sleepiness or fatigue: sometimes lasting into the evening
  • Nausea: often preventable with food timing and a calm setting
  • Headache: can occur later the same day
  • Unpleasant taste or throat drip: from nasal drainage

These usually peak during the session and improve as the observation window ends, though tiredness can linger.

Blood pressure increases: esketamine can temporarily raise blood pressure. Clinics check vitals before dosing and again afterward. This is one reason medical screening matters. If you already have hypertension, your prescriber may coordinate with primary care or cardiology to optimize treatment and reduce risk.

Cognition and coordination: even if you feel “fine,” reaction time and judgment can be affected. Most programs advise against driving, biking in traffic, operating machinery, or signing important documents until the next day. Plan transportation in advance every time—do not rely on how you felt last session.

Mental health risks: while many people feel calmer, a minority may feel anxious, panicky, or emotionally raw during treatment. If you have trauma, the dissociative state can occasionally pull up old fear sensations. This is not a reason to avoid treatment automatically, but it is a reason to prepare: discuss grounding strategies, consider therapy support during the treatment month, and be honest about your history.

Misuse and dependence concerns: esketamine is administered in a controlled setting for a reason. Repeated dissociative experiences can be psychologically reinforcing for some people, especially those with substance use vulnerability. A good clinic takes this seriously: they screen, monitor, and treat the medication as medical care—not as an experience to chase.

What to report quickly: contact your clinic promptly if you experience chest pain, severe headache, fainting, severe agitation, new hallucinations outside sessions, or worsening suicidal thoughts. “White-knuckling” through side effects is not a badge of toughness; it is a risk.

Safety with esketamine is largely about structure: careful selection, clear boundaries, and consistent monitoring. When those are in place, most patients can complete treatment with manageable and time-limited side effects.

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Practical planning, costs, and alternatives

If you are considering esketamine, practical planning is not optional—it is part of the treatment. People who do best often treat the month of induction like a temporary medical program with protected time, rather than something they “fit in.”

Scheduling and recovery time: sessions can take a significant part of a day when you include travel, dosing, observation, and the post-visit slump. Try to:

  1. Block the rest of the day from high-stakes tasks.
  2. Arrange a consistent ride plan (one person, rideshare, or clinic-supported transport).
  3. Prepare a simple post-treatment routine: hydration, light meal, low stimulation, early bedtime.

Work and family logistics: it can help to tell at least one trusted person what you are doing—not for permission, but for support. A simple explanation is enough: “I’m doing a clinic treatment that can make me drowsy afterward, so I may be offline those afternoons.”

Cost and insurance: costs vary widely by country and insurance plan. In many systems, coverage requires prior authorization and documentation of treatment resistance. Ask the clinic staff what they typically need:

  • a record of prior antidepressant trials
  • diagnosis history and symptom severity
  • psychotherapy history
  • medical clearance notes if you have blood pressure or vascular risks

How it compares with other options: esketamine is one tool among several for difficult-to-treat depression.

  • Medication optimization and augmentation: sometimes changing strategy (dose, class, or adding an augmentation agent) offers comparable benefit without clinic visits.
  • Transcranial magnetic stimulation (TMS): noninvasive neuromodulation with a different side-effect profile; often requires frequent weekday sessions for several weeks.
  • Electroconvulsive therapy (ECT): highly effective for certain severe depressions, especially when rapid response is needed; involves anesthesia and a distinct risk-benefit profile.
  • IV ketamine: used off-label in some settings; evidence supports rapid effects, but regulation and monitoring standards vary, and insurance coverage can be inconsistent.
  • Trauma-focused therapy and skills-based therapies: for many people, symptom relief becomes durable only when nervous-system patterns are addressed alongside biology.

Planning for the “after” phase: if esketamine helps, the next step is protecting the gains. This often means deciding what maintenance looks like and using the improved breathing room to strengthen basics: sleep regularity, therapy attendance, movement, social connection, and relapse planning. The goal is not to stay in crisis care forever—it is to move from rescue to stability.

A final practical note: if your clinic feels rushed, unclear, or dismissive about safety—take that seriously. Esketamine can be helpful, but it should never be casual. The right setting is part of the medicine.

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References

Disclaimer

This article is for educational purposes and does not replace medical advice, diagnosis, or treatment. Esketamine is a prescription treatment that requires individualized screening and monitoring; the safest plan depends on your medical history, current medications, substance use risk, and symptom severity. If you are considering esketamine—or if you have worsening depression or suicidal thoughts—seek help from a qualified clinician promptly. If you feel at immediate risk of harm, contact local emergency services right away.

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