How Long Does it Take for Spravato to Work?

Matt Rodriguez • April 1, 2025

Spravato (esketamine) is a groundbreaking treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation (MDSI). Unlike traditional antidepressants, Spravato works rapidly, often providing symptom relief within hours. In this article, we’ll introduce Spravato, discuss how long it takes to work, and explore its short- and long-term effects.

What is Spravato and How Does It Work?

Spravato (esketamine) is an FDA-approved nasal spray derived from ketamine, specifically designed to treat individuals with TRD and MDSI.

Like ketamine, Spravato works by inhibiting NMDA receptors—proteins involved in learning and memory. This inhibition leads to the release of glutamate, a key neurotransmitter, triggering several downstream effects in brain cells.

Unlike standard antidepressants, Spravato has rapid-acting effects, sometimes appearing almost immediately after use. It also offers sustained benefits compared to conventional medications and doesn’t require daily use.

Short- and Long-Term Effects of Spravato on the Brain

Immediate Effects

Spravato enhances activity in brain regions responsible for mood regulation, which are often underactive in depression. This effect can occur within hours, often within 24 hours, leading to symptom relief and an improved mood.

Long-Term Effects

Over time, repeated doses of Spravato strengthen connections between nerve cells through neuroplasticity. Spravato stimulates the production of proteins that support this process, reinforcing neural circuits linked to mood and emotional regulation. Neuroplasticity may explain Spravato’s prolonged improvements in depression.


How Long Does It Take for Spravato to Work?

Clinical trials have shown that Spravato can quickly reduce symptoms of depression, often within hours or days.

In a study of adults with TRD, those who took Spravato along with an antidepressant experienced noticeable symptom relief within 24 hours—an improvement greater than those who took a placebo with an antidepressant. Both groups continued improving over the next 28 days, but the difference between them remained significant.

For people with MDSI, clinical studies have shown that Spravato, combined with an antidepressant, significantly reduces symptoms within 24 hours compared to placebo groups. The greatest differences are seen within four hours of taking the medication.

Factors That Affect How Long Spravato Takes to Work

The time it takes for Spravato to start working varies from person to person. Some may feel relief within hours, while others may require several treatments over days or weeks to notice significant changes. Factors that influence how quickly Spravato works include:

  • Severity of Depression – Those with more severe symptoms may take longer to notice improvement.
  • Individual Brain Chemistry – Differences in neurotransmitter activity can affect response time.
  • Previous Treatments – If someone has had multiple unsuccessful treatments, their response may be slower.
  • Overall Health – Chronic illnesses or nutritional deficiencies may impact treatment effectiveness.
  • Psychological and Environmental Factors – Stress levels, support systems, and therapy participation can all play a role.

How Long Do the Effects of Spravato Last?

A single dose of Spravato provides relief for up to 24 hours, but for sustained benefits, treatment follows a structured regimen:

Induction Phase

  • Twice-weekly doses for the first four weeks.

Maintenance Phase

  • Begins after Week 4, with dosing frequency gradually reduced based on clinical response—typically shifting to once weekly or every two weeks.

A long-term study found that 35.6% of patients achieved remission after the induction phase, and 46.1% remained in remission during the maintenance phase. On average, patients in the maintenance phase had used Spravato for just over three years, indicating its continued benefits with long-term use.

Spravato Short-Term Side Effects 

While Spravato is generally well tolerated, mild side effects are common, including:

  • Dizziness
  • Nausea
  • Sedation or drowsiness
  • Dissociation (feeling detached from one’s body or reality)
  • Increased blood pressure
  • Anxiety or restlessness
  • Elevated mood or euphoria

These side effects typically wear off within a few hours but can linger for up to 24 hours.

Safety Considerations

  • Monitoring: Spravato is administered in a certified healthcare setting under medical supervision. Patients are monitored for at least two hours post-dose for potential side effects.
  • Driving Restrictions: Due to possible sedation and dissociation, patients should not drive or operate heavy machinery until the following day after a full night’s rest.

Potential Long-Term Risks of Spravato

Ketamine is a drug of abuse with addictive properties. Chronic misuse has been linked to long-term effects such as cognitive impairment and damage to the bladder, liver, and kidneys.

However, Spravato is administered in a controlled clinical environment, significantly reducing the risk of misuse. While it has not been extensively studied in patients with pre-existing substance abuse disorders, those with addiction histories may be at higher risk.

Physically, Spravato appears safe for long-term use, though some evidence suggests users may experience bladder-related symptoms. However, clinical trials have found no significant difference in bladder infections between Spravato and non-Spravato patients.


Spravato Treatment at SW Florida TMS & Ketamine Clinic

At Southwest Florida TMS & Ketamine Clinic, we specialize in innovative depression treatments, including Spravato therapy for individuals with TRD. If you’re struggling with depression and haven’t found relief from conventional therapy, our services, based in Fort Myers, could have the solution you need. Spravato is a fast-acting medication with sustained benefits, and our team is highly experienced in delivering this medicine with expert care. 

If you choose to have treatment at our service, we will closely monitor you during and after administration and will be here to provide support after and between doses. 

For more information on Spravato treatment and to schedule a consultation, visit our Spravato Clinic page.

Key Takeaways

  • Rapid Relief: Many patients experience symptom improvement within hours or days of starting Spravato.
  • Mechanism of Action: Spravato enhances mood-regulating brain activity and promotes neuroplasticity.
  • Individual Variability: Factors like depression severity, brain chemistry, and past treatments influence response time.
  • Sustained Benefits: With continued treatment, Spravato strengthens neural connections, supporting long-term depression relief.
  • Safety Considerations: While generally well-tolerated, Spravato requires medical supervision due to potential side effects and driving restrictions.

Expert Care at SW Florida TMS & Ketamine Clinic: Offering specialized Spravato therapy with close monitoring and personalized treatment plans for patients with TRD.

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