Spravato Monotherapy: Can You Take It Without an Antidepressant?

The short answer, for many adults with treatment-resistant depression: yes. On January 17, 2025, the FDA expanded the label for SPRAVATO® (esketamine) nasal spray so that, for treatment-resistant depression (TRD) in adults, it can be used as monotherapy (on its own) or together with an oral antidepressant. The Spravato monotherapy approval left a lot unchanged: Spravato's other approved use, its restricted safety program, the monitoring of at least 2 hours after every dose and the driving rule are all the same. And it does not mean you should stop the antidepressant you take now. Whether you keep it is a decision you make with your prescriber, based on your own history.

What exactly did the FDA change in 2025?

Spravato was first approved in March 2019 for TRD in adults, used with an oral antidepressant. In 2020 the FDA added a second use: depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal thoughts or behavior, also with an oral antidepressant.

The 2025 change touched only the first of those. The FDA's approval letter is dated January 17, 2025, and Johnson & Johnson announced it on January 21. The current prescribing information (revised March 2026) now reads that Spravato is for adults with TRD "as monotherapy or in conjunction with an oral antidepressant."

That is why you may still find web pages, including some clinic pages, saying Spravato must always be taken with an antidepressant. That wording reflects the label as it stood before 2025. The label itself is the same everywhere, but your prescriber or your insurance plan may still have reasons to keep an oral antidepressant in the plan (see below).

What stayed the same?

More than you might expect. The monotherapy approval widened one option; it did not loosen any of the safety requirements.

• The suicidal-thoughts indication still requires an oral antidepressant. For adults with MDD and acute suicidal thoughts or behavior, Spravato is used together with an oral antidepressant. The label also states that Spravato has not been shown to prevent suicide or to reduce suicidal thoughts or actions. If you are thinking about suicide, call or text 988 now.
• It is still for treatment-resistant depression. TRD usually means depression that hasn't improved enough after at least two antidepressants of adequate dose and duration in the current episode. The FDA indication itself does not set a number. "Monotherapy" does not make Spravato a first treatment. Our guide on who may qualify for Spravato explains the usual criteria.
• It is still given only in certified clinics. Spravato is available only through the SPRAVATO REMS. You use the nasal spray yourself under a clinician's supervision, and it is never taken home.
• Monitoring is still at least 2 hours, every session. Blood pressure is checked before the dose and again about 40 minutes after.
• The driving rule is the same. No driving or operating machinery until the next day after a restful sleep. Plan for someone to drive you home after every session.
• It is still for adults only. Spravato is not approved for anyone under 18.
• The schedule is the same. Sessions are twice weekly in weeks 1 to 4, weekly in weeks 5 to 8, then weekly or every two weeks.

What did the Spravato monotherapy study find?

The approval rested on a randomized, double-blind, placebo-controlled trial lasting 4 weeks, described in the prescribing information. It enrolled 378 adults with TRD. They received Spravato 56 mg (86 people), Spravato 84 mg (95 people) or a placebo spray (197 people) twice a week, and nobody in the trial took an oral antidepressant.

Researchers measured depression with the MADRS, a clinician-rated scale from 0 to 60 where lower is better. At Day 28:

• People on 56 mg improved by 5.1 points more than people on placebo.
• People on 84 mg improved by 6.8 points more than people on placebo.
• Both differences were statistically significant, and per the prescribing information, both doses were already ahead of placebo by Day 2. Results vary from person to person, and a full course is usually needed.

Johnson & Johnson reported that 22.5% of people on Spravato were in remission at week 4 (a MADRS score of 12 or lower), compared with 7.6% on placebo. The press release does not say how the two doses were combined, and the prescribing information does not report a remission rate for this trial, so treat it as a manufacturer-reported figure. It also means most people in the trial had not reached remission after 4 weeks.

Side effects in this trial followed the familiar pattern. In the adverse reactions section of the current label (the DailyMed entry, revised March 2026), dissociation was reported by 28% on Spravato vs 4% on placebo, nausea by 25% vs 8%, dizziness by 22% vs 7% and headache by 19% vs 9%.

Two limits are worth keeping in mind. The placebo-controlled data cover only 4 weeks. And because the placebo group in this trial received no antidepressant at all, while the placebo groups in the earlier combination trials started a new oral antidepressant, the numbers from these studies can't be lined up side by side.

Who decides whether I keep taking my oral antidepressant?

Your prescriber, with you, and for your situation specifically. For TRD, the label leaves room for both approaches — nowhere does it say one is right for everyone.

Questions worth bringing to that conversation:

• Is my current antidepressant giving me partial benefit, even if it isn't enough on its own?
• Are its side effects a reason to consider stopping it, now or later?
• If we change anything, who makes the change and how gradually?
• What does my insurance plan require (see below)?

One firm rule: do not stop or change any medication on your own to make Spravato fit. Stopping psychiatric medication abruptly can be harmful, and changes should come from the clinician who prescribed it. If you notice you feel worse after any medication change, tell your prescriber promptly; our article on feeling worse after starting a new psychiatric medication covers what to watch for. If you have thoughts of suicide, call or text 988.

If your antidepressant is managed by a different clinician than the one who would oversee Spravato, the two offices need to agree on who handles which prescription. See questions to ask if your current prescriber doesn't offer Spravato.

Will my insurance cover Spravato without an antidepressant?

This section covers one narrow question: whether a plan's criteria still require a concurrent oral antidepressant now that the label allows monotherapy. For the broader picture — prior authorization, what plans typically require and what happens when they say no — see our guide on whether insurance covers Spravato in Texas.

Payer policies did not all update at the same pace as the label. Three policies in our research show the range on the monotherapy criterion specifically:

• UnitedHealthcare (commercial and Individual Exchange), policy effective May 1, 2026: allows Spravato for TRD as monotherapy or with an oral antidepressant. It also requires at least two failed antidepressants at an adequate dose for 8 weeks or more each, a baseline depression rating scale and psychiatrist involvement.
• Texas Medicaid: TMHP announced a prior authorization update for esketamine allowing monotherapy for adults 18 and older with TRD, effective October 1, 2025. Before that, at least one Medicaid managed care plan — Texas Children's Health Plan, in a provider alert — allowed monotherapy effective May 1, 2025. Medicaid managed care plans may use procedures that differ from traditional Medicaid and from one another.
• Blue Shield of California (commercial), policy effective March 1, 2026: the policy text as we recorded it still lists a concurrent oral antidepressant as required for TRD.

Other plans were not reviewed for this article. Policies change, so confirm your plan's current criteria with your insurer. You can also find general information on our insurance and payment page. Coverage is decided by your plan, and an evaluation is a separate step from insurance approval.

Where does MindVibe offer Spravato?

MindVibe runs REMS-certified Spravato treatment centers in Texas and California, all listed on our Spravato treatment page. In Texas, that means Houston; in California, Fresno, Arroyo Grande, Palm Desert and San Diego.

We also offer psychiatric evaluation and medication management as part of depression treatment, with telehealth for follow-up visits where appropriate. Spravato itself is always given in person at a certified center. If you want to talk through whether Spravato, with or without an oral antidepressant, makes sense for you, you can request an appointment.

Important safety information

Spravato (esketamine) nasal spray, CIII, is a prescription medicine with two approved uses: in adults with treatment-resistant depression, taken either on its own or alongside an oral antidepressant, and — always paired with an oral antidepressant — for depressive symptoms in adults who have major depressive disorder with suicidal thoughts or actions. Spravato is not approved as an anesthetic, nor has it been shown to prevent suicide.

Spravato carries a Boxed Warning. Because it can cause sedation, dissociation (a sense of being disconnected from yourself, your thoughts or your surroundings) and respiratory depression (slowed breathing), a healthcare provider monitors you for at least 2 hours after every dose. It has a potential for abuse and misuse. Antidepressants may increase suicidal thoughts and behaviors in people 24 and younger; call your provider right away about new or worsening depression or suicidal thoughts. Spravato is available only through a restricted program, the SPRAVATO REMS, and is given only in certified healthcare settings. Do not drive or operate machinery until the next day after a restful sleep.

Read the full Prescribing Information, including the Boxed Warning, and the Medication Guide.

If you are in crisis: call or text 988 to reach the Suicide & Crisis Lifeline, available 24/7, or call 911 or go to the nearest emergency room if you or someone else is in immediate danger.

Sources

• SPRAVATO (esketamine) Prescribing Information, Janssen Pharmaceuticals / Johnson & Johnson, revised March 2026: https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
• SPRAVATO Prescribing Information, rev. 04/2025 (monotherapy study design and results): https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211243s019lbl.pdf
• DailyMed, SPRAVATO label (revised 3/2026; monotherapy adverse reactions): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d81a6a79-a74a-44b7-822c-0dfa3036eaed
• FDA approval letter, NDA 211243 S-016 (January 17, 2025): https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/211243Orig1s016ltr.pdf
• Johnson & Johnson press release, monotherapy approval (January 21, 2025): https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression
• UnitedHealthcare, Ketalar and Spravato Commercial and Individual Exchange Medical Benefit Drug Policy 2026D0069Q (effective May 1, 2026): https://www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/ketalar-spravato.pdf
• Texas Children's Health Plan, Prior Authorization Updates for Esketamine (Spravato) Effective May 1, 2025, for Texas Medicaid: https://www.texaschildrenshealthplan.org/news/provider-alert/prior-authorization-updates-esketamine-spravato-effective-may-1-2025-texas
• TMHP, Texas Medicaid Prior Authorization Update for Esketamine (Spravato) Effective October 1, 2025: https://www.tmhp.com/news/2025-09-12-texas-medicaid-prior-authorization-update-esketamine-spravato-effective-october-1
• Blue Shield of California, esketamine (Spravato) Commercial Medical Benefit Drug Policy (effective March 1, 2026): https://www.blueshieldca.com/content/dam/bsca/en/provider/docs/bsc-med-benefit-drug-policy/esketamine-Spravato-COMM-UMRx-provider.pdf

Frequently asked questions

Is Spravato approved on its own for everyone with depression?

No. Spravato on its own (monotherapy) is approved only for adults with treatment-resistant depression, which usually means depression that hasn't improved enough after at least two antidepressants. When it's prescribed for depressive symptoms in adults with major depressive disorder and acute suicidal thoughts or behavior, an oral antidepressant is still part of the picture. Spravato is not approved for anyone younger than 18.

When was Spravato approved as monotherapy?

The FDA approval letter is dated January 17, 2025, and Johnson & Johnson announced the approval on January 21, 2025. Since then, the label has allowed Spravato for treatment-resistant depression in adults either on its own or together with an oral antidepressant. The current prescribing information, revised March 2026, uses that wording.

Should I stop my antidepressant if I start Spravato?

Not on your own. The label allows Spravato for treatment-resistant depression with or without an oral antidepressant, but which approach fits you is a decision for your prescriber. Stopping psychiatric medication abruptly can be harmful. Ask the clinician who prescribes your antidepressant before making any change, and report it promptly if you feel worse after a change. If you have thoughts of suicide, call or text 988.

Does taking Spravato without an antidepressant change the 2-hour monitoring?

No. Every session still happens at a REMS-certified healthcare setting, you use the spray under supervision, and you are monitored for at least 2 hours afterward. You still cannot drive or operate machinery until the next day after a restful sleep, so plan for someone to drive you home after each session.

Will my insurance cover Spravato without an oral antidepressant?

Requirements vary by plan. UnitedHealthcare's commercial policy effective May 1, 2026 allows monotherapy for treatment-resistant depression, and TMHP announced a Texas Medicaid prior authorization update allowing monotherapy effective October 1, 2025. Blue Shield of California's commercial policy text, as we recorded it, still lists a concurrent oral antidepressant as required. Most plans require prior authorization, so confirm current criteria with your insurer.

Why do some websites say Spravato must be taken with an antidepressant?

Before January 2025, that was accurate for treatment-resistant depression. The original 2019 approval required an oral antidepressant, and many pages written before the label changed haven't been updated. The current label allows treatment-resistant depression to be treated with Spravato alone or with an oral antidepressant. The suicidal-thoughts indication still requires an oral antidepressant.

This article is for educational purposes only and is not medical advice, a diagnosis, or a treatment recommendation. Talk with your own clinicians before making any change to your care.