How SPRAVATO® Differs From Standard Oral Antidepressants

September 1, 2026

For many people with depression, treatment begins with an oral antidepressant. These medications can be effective, but some patients continue to experience significant symptoms despite trying appropriate treatments. In certain situations, a psychiatrist may consider a different approach, including SPRAVATO® (esketamine) nasal spray.



SPRAVATO is not simply another version of a traditional antidepressant. It differs in how it is administered, how it acts in the brain, how quickly treatment is structured, and the level of medical supervision required.

SPRAVATO Targets a Different Brain System

Many commonly prescribed oral antidepressants affect neurotransmitter systems involving serotonin, norepinephrine, or dopamine.


SPRAVATO works differently. Esketamine is an antagonist of the NMDA receptor, which is part of the brain’s glutamate signaling system. The precise mechanism responsible for its antidepressant effect is not fully understood. 


This different mechanism is one reason SPRAVATO may be considered for adults with treatment-resistant depression, particularly after other antidepressant approaches have not produced an adequate response.


It Is a Nasal Spray Rather Than a Daily Pill

Standard antidepressants are usually taken orally at home on a daily schedule.


SPRAVATO is administered as a nasal spray in a certified healthcare setting. Patients do not receive the medication to take home.


For treatment-resistant depression, the current prescribing information generally uses a more frequent schedule during the initial treatment phase, followed by less frequent maintenance treatments when appropriate. Treatment frequency is individualized based on response and tolerability. 



That makes SPRAVATO a substantially different treatment experience from taking a medication once each day.

Medical Monitoring Is Required

One of the most important differences is the level of supervision.


SPRAVATO is available only through a restricted safety program known as the SPRAVATO REMS. Because treatment can cause sedation, dissociation, respiratory depression, increases in blood pressure, and other effects, it must be administered under medical supervision.


Patients are monitored for at least two hours following each treatment session before a healthcare professional determines that they are ready to leave. 


Patients also should not drive or operate machinery until the following day after a restful sleep.


SPRAVATO Has Specific FDA-Approved Uses

SPRAVATO is FDA-approved for treatment-resistant depression in adults. Current prescribing information allows it to be used either as monotherapy or together with an oral antidepressant for treatment-resistant depression. 


It is also approved, in conjunction with an oral antidepressant, for depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior. 



These indications differ from those of many standard antidepressants, which may be prescribed across a broader range of depressive or anxiety disorders depending on the specific medication.

Treatment Decisions Depend on the Individual

SPRAVATO is not automatically the next step whenever an antidepressant does not work.


A psychiatrist may consider previous medication trials, diagnoses, symptom severity, side effects, medical history, current medications, treatment preferences, and other factors before recommending a change in treatment.


For some patients, adjusting medication may remain appropriate. Others may be candidates for TMS or SPRAVATO. The goal is to determine which evidence-based option best fits the individual rather than applying the same treatment sequence to everyone.


Side Effects Are Different as Well

Oral antidepressants can cause side effects such as gastrointestinal symptoms, sleep changes, sexual side effects, or changes in appetite, depending on the medication.


SPRAVATO has a different safety profile. Its prescribing information includes warnings regarding sedation, dissociation, respiratory depression, abuse and misuse, and increased blood pressure, among other risks.



The required monitoring period allows clinicians to observe patients during the period when these effects may occur.

Exploring Options Beyond Standard Antidepressants

SPRAVATO and conventional oral antidepressants both play roles in modern depression treatment, but they are substantially different therapies. SPRAVATO acts through a different neurochemical pathway, is given intranasally in a certified medical setting, and requires observation after each treatment.


Apex Interventional Psychiatry provides psychiatric evaluation, medication management, TMS, and SPRAVATO treatment for appropriate patients. If depression symptoms have continued despite previous medication treatment, contact Apex Interventional Psychiatry to discuss whether a different treatment strategy may be appropriate.

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Why TMS May Be Considered After Antidepressants Have Not Worked Well Enough

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Antidepressants are often an important part of depression treatment, but they do not work equally well for everyone. Some people experience only partial improvement, while others continue to have significant symptoms despite trying more than one medication.  When depression remains difficult to treat, a psychiatrist may consider additional options such as transcranial magnetic stimulation, or TMS . TMS is a noninvasive treatment that uses magnetic pulses to stimulate areas of the brain involved in mood regulation. It is commonly considered when standard approaches have not provided enough relief.

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