Spravato vs. Traditional Antidepressants: Which Is Better for Treatment-Resistant Depression?

When depression does not improve after multiple treatment attempts, it can be discouraging to consider another medication. You may wonder whether continuing to try traditional antidepressants makes sense or whether a newer treatment such as Spravato® could be a better option.
 
The answer depends on your diagnosis, treatment history, symptoms, medical needs, and preferences. Spravato is not automatically better than traditional antidepressants, and it is not appropriate for everyone. However, it may offer another evidence-based option for adults with treatment-resistant depression.
 
At Roundtree Mental Health Group, we evaluate your full history and work with you to create a personalized treatment plan. Learn more about our Spravato treatment services or schedule an appointment to discuss your options.

Understanding Treatment-Resistant Depression

Treatment-resistant depression generally refers to depression that does not improve sufficiently after at least two adequate antidepressant trials. An “adequate” trial typically means taking a medication at an appropriate dose for enough time, as recommended by your prescribing clinician.
 
Depression symptoms can include persistent sadness, loss of interest, fatigue, sleep changes, appetite changes, difficulty concentrating, hopelessness, or thoughts of death or suicide. Symptoms may look different from person to person, and another condition, medication, or medical issue can sometimes contribute to them.
 
A thorough psychiatric evaluation helps clarify your diagnosis and treatment history. It also gives your provider an opportunity to review medication adherence, side effects, co-occurring conditions, substance use, sleep, and other factors that may affect treatment response.

How Traditional Antidepressants Work

Traditional antidepressants include medication classes such as selective serotonin reuptake inhibitors, or SSRIs, and serotonin-norepinephrine reuptake inhibitors, or SNRIs. Other options include atypical antidepressants, tricyclic antidepressants, and monoamine oxidase inhibitors.
 
These medications primarily affect chemical signaling involving serotonin, norepinephrine, or dopamine. They are commonly used as first-line treatments for depression and may also help with anxiety disorders, obsessive-compulsive disorder, and other conditions.
 
Traditional antidepressants offer several practical benefits:
  • They are usually taken at home.
  • They do not require monitored treatment sessions after every dose.
  • Many have been used for decades and have well-established safety information.
  • They may be effective for people experiencing a first depressive episode or depression that has not yet become treatment-resistant.
Antidepressants usually take time to work. According to the National Institute of Mental Health, many people need approximately four to eight weeks to evaluate the full effect of an antidepressant, although some symptoms may improve sooner.
 
If a medication is not effective or causes difficult side effects, your provider may adjust the dose, switch medications, or consider another treatment strategy. Medication decisions should be made with professional guidance rather than by stopping treatment suddenly.

How Spravato Is Different

Spravato is the brand name for esketamine nasal spray. It works through a different pathway than traditional antidepressants, including effects on the brain’s glutamate system and NMDA receptors.
 
This difference matters because a medication that works through another pathway may help some people whose depression has not responded to multiple traditional antidepressants. Spravato is FDA-approved for adults with treatment-resistant depression. The current FDA labeling allows it to be used alone or with an oral antidepressant for this indication. It is also approved, in combination with an oral antidepressant, for certain adults with major depressive disorder and acute suicidal ideation or behavior.
 
You can review prescribing information in the FDA-approved Spravato label and learn more from the manufacturer at Spravato.com.
 
Spravato is not a medication that you take home. It must be administered in a certified healthcare setting under medical supervision.

Speed of Relief May Be an Important Difference

One of the most discussed differences between Spravato and traditional antidepressants is the potential speed of symptom improvement.
Traditional antidepressants often require several weeks before you and your provider can determine whether they are helping. Spravato may begin reducing depressive symptoms more quickly for some patients, sometimes within hours or days. A rapid response can be particularly important when symptoms are severe or when depression has continued despite multiple treatments.
However, a faster potential onset does not mean Spravato provides immediate or guaranteed relief. Your provider will monitor your response over time and may recommend Spravato as part of a broader plan that includes medication management, psychotherapy, lifestyle support, or other services.
If you are experiencing thoughts of suicide or feel unable to stay safe, seek immediate help. Call or text 988 for the Suicide & Crisis Lifeline, call 911, or go to the nearest emergency department. Spravato treatment is not a substitute for emergency crisis care.

Comparing the Treatment Experience

The treatment process is one of the clearest differences between Spravato and traditional antidepressants.
 
At Roundtree Mental Health Group, Spravato sessions include observation after dosing. Patients should plan for a treatment visit that takes time and should arrange transportation according to their provider’s instructions. You should not drive or operate machinery after treatment until you have followed the medication’s safety guidance and are fully recovered.

Safety and Eligibility Matter

Spravato is not appropriate for everyone. Your provider will review your medical history, current medications, blood pressure, cardiovascular health, psychiatric symptoms, substance use history, and previous depression treatments.
 
Spravato is a Schedule III controlled substance. Its supervised administration helps reduce the risk of misuse and allows the clinical team to monitor for side effects such as:
  • Dissociation or a sense of being disconnected from your surroundings
  • Drowsiness or sedation
  • Dizziness or impaired coordination
  • Nausea
  • Temporary increases in blood pressure
These effects are often temporary, but they require appropriate monitoring. Tell your provider about all prescription medications, over-the-counter products, supplements, alcohol use, and other substances before treatment.

Which Option May Be Better for You?

Spravato may be worth discussing if:
  • You have major depressive disorder.
  • You have tried at least two antidepressants without sufficient improvement.
  • Side effects or slow progress have made additional traditional medication trials difficult.
  • You are able to attend supervised treatment sessions.
  • Your provider determines that Spravato is medically appropriate.
  • You are interested in a treatment that works through a different mechanism.
Traditional antidepressants may remain a reasonable choice if you are beginning treatment, have not yet tried an adequate medication regimen, prefer home-based dosing, or have a medical condition that makes Spravato unsuitable.
 
In some cases, the best plan includes both approaches. Current FDA labeling allows Spravato to be used alone or with an oral antidepressant for adult treatment-resistant depression, but your provider will determine whether that approach fits your circumstances.
 
Our psychopharmacology services focus on careful medication review, rational prescribing, avoidance of unnecessary polypharmacy, and ongoing monitoring. The goal is not to prescribe more medication. The goal is to identify a treatment plan that makes sense for you.

What to Expect at Roundtree Mental Health Group

Roundtree Mental Health Group is a certified Spravato treatment center serving Lebanon and surrounding communities. We begin with a careful review of your symptoms, diagnosis, previous medications, medical history, and treatment goals.
If Spravato appears appropriate, we explain the treatment process, safety requirements, monitoring expectations, and next steps. We provide compassionate, structured care so you can make informed decisions without feeling rushed or pressured.
 
Appointments are available in person in Lebanon and through secure telehealth services throughout Tennessee when clinically appropriate. Because Spravato must be administered under supervision, treatment sessions take place in person at our certified center.

Take the Next Step Toward Personalized Care

There is no single best depression treatment for every person. Traditional antidepressants remain helpful for many people, while Spravato can provide an important option for eligible adults with treatment-resistant depression.
 
A thorough evaluation can help you understand whether another traditional antidepressant trial, Spravato, psychotherapy, or a combination of treatments may best support your recovery.
 
Contact Roundtree Mental Health Group or call or text 931-288-4619 to speak with our team.
 
> This article is for informational and educational purposes only and does not provide medical advice. Do not start, stop, or change psychiatric medication without consulting a qualified healthcare professional. Spravato eligibility and treatment plans are determined individually. If you are experiencing a mental health emergency, call 911, call or text 988, or go to the nearest emergency department.