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The FDA label
What SPRAVATO is approved for, in the label's own words
The label approves two uses. Neither is an anxiety disorder.
“SPRAVATO is indicated for the treatment of: Treatment-resistant depression (TRD) in adults as monotherapy or in conjunction with an oral antidepressant; Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.”
The label adds limits. It says the effectiveness of SPRAVATO “in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.” It also says SPRAVATO is only available through a restricted program, the SPRAVATO REMS.
“Treatment-resistant” has a meaning in the trials. Patients in the main short-term study had major depression and, in the current episode, “had not responded adequately to at least two different antidepressants of adequate dose and duration.” The table sets out where anxiety fits.
| Situation | FDA status | What the evidence shows |
|---|---|---|
| Treatment-resistant depression, with anxiety symptoms | Approved for the depression, not for the anxiety. | A post hoc analysis of the main 4-week trial: depression scores fell more with SPRAVATO than with placebo whether or not anxiety was present. Anxiety scores were not the outcome. |
| Major depression with acute suicidal thoughts or behavior, with anxiety symptoms | Approved for the depressive symptoms, with an oral antidepressant. | No anxiety-specific result is given in the label for this use. |
| Generalized anxiety, social anxiety or panic disorder without depression | Not approved. Any use would be off-label. | A 2026 systematic review of 78 studies found no esketamine study in a primary anxiety disorder. The 11 studies it found used ketamine. |
| Anxiety caused by the treatment itself | Listed in the label as a common side effect. | 13 percent with SPRAVATO and an oral antidepressant, against 6 percent with placebo and an oral antidepressant. |
Label wording from the SPRAVATO prescribing information on DailyMed (version effective September 22, 2026), read October 29, 2026.
Why the question comes up
Anxiety and treatment-resistant depression usually come together
Most people asking about SPRAVATO for anxiety have depression that has not lifted, with anxiety on top. That pairing is common, and it makes depression harder to treat.
- In the STAR*D study, 53.2 percent of patients starting antidepressant treatment had anxious depression. They did worse on antidepressants than patients without it.
- In a Dutch cohort, 54.2 percent of people with major depression met the DSM-5 label “with anxious distress.” It predicted a chronic course better than an anxiety disorder diagnosis did.
- In the main SPRAVATO trial, about 72 percent of patients (162 of 223) had significant anxiety symptoms or an anxiety disorder.
- A 2026 review in CNS Drugs found that anxiety in major depression goes with greater severity, more suicidality, and lower functioning.
Our TMS for anxiety guide explains how anxious depression is measured, and where TMS is FDA-cleared for anxiety symptoms in depression.
The trial data
What the SPRAVATO trials show when anxiety is present
The SPRAVATO trials were not designed to treat anxiety. Researchers went back to them afterwards and split patients by anxiety. Here is what they found.
Depression improved with or without anxiety
In the 4-week trial, patients with anxiety on SPRAVATO and an oral antidepressant dropped 21.0 points on average on the depression scale. Patients without anxiety dropped 22.7.
The gap over placebo
With anxiety, SPRAVATO beat placebo by 4.2 points. Without anxiety, by 7.5 points. The authors found no significant difference between the two groups (p = .371).
Anxiety lowered the odds
A pooled analysis of two 4-week trials found response and remission more likely in SPRAVATO patients without significant anxiety at the start.
Who wrote it
Both analyses were post hoc and led by researchers at Janssen, the maker of SPRAVATO. Neither measured whether anxiety itself got better.
A 2026 review in CNS Drugs reached the same limit. It said ketamine and esketamine have been shown to improve depression or anxiety symptoms in depression with anxiety. But it added that the evidence is mainly short-term, from post hoc analyses of trials not designed to measure anxiety. It called for trials with anxiety as the main outcome.
Off-label use
Esketamine for anxiety disorders without depression: what exists
Almost nothing for esketamine. The research on anxiety disorders alone is about ketamine, a related but different medicine, in mostly small studies.
- A 2026 systematic review screened 4,086 results and included 78 studies. Eleven studied people whose main problem was an anxiety disorder. All 11 used ketamine; no esketamine study was found.
- The review found that ketamine or esketamine was linked to less anxiety. It also found that anxiety may return soon after maintenance treatment stops.
- In one small 2017 study, 12 people with hard-to-treat generalized or social anxiety received ketamine injections. Ten of the 12 responded.
- A follow-up gave 20 of those responders weekly ketamine for 3 months, with no placebo group. One hour after dosing, anxiety ratings fell by about half.
- A 2026 review of treatment-resistant anxiety disorders rated ketamine as preliminary, open-label evidence only.
Ketamine is not SPRAVATO. They are not interchangeable products or regulatory pathways, as our ketamine overview explains. When anxiety without depression is the reason, SPRAVATO would be an off-label use.
Side effects
SPRAVATO can also cause anxiety
Anxiety is one of the label's common side effects. In every trial table below, it was reported more often with SPRAVATO than with placebo.
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| Trials in the label | Anxiety with SPRAVATO | Anxiety with placebo |
|---|---|---|
| Treatment-resistant depression, with an oral antidepressant (label Table 3) | 45 of 346 (13%) | 14 of 222 (6%) |
| Treatment-resistant depression, SPRAVATO alone (label Table 4) | 22 of 226 (10%) | 8 of 250 (3%) |
| Major depression with acute suicidal thoughts or behavior, with an oral antidepressant | 34 of 227 (15%) | 20 of 225 (9%) |
- The label's “anxiety” counts several terms together, including agitation, fear, feeling jittery, nervousness, panic attack and tension.
- Anxiety was the most frequent side effect that led people to stop SPRAVATO across the phase 3 studies, at 1.2 percent.
- Patients are monitored for at least 2 hours at each session, then checked before they leave.
- The Medication Guide asks patients to call their provider about new or worse anxiety, or panic attacks.
Our SPRAVATO side effects page covers dissociation, blood pressure and the other label rates.
How to get SPRAVATO
The path starts with a psychiatric evaluation
SPRAVATO is only given in certified healthcare settings, through the SPRAVATO REMS safety program. A psychiatrist decides first whether it fits.
Labyrinth Psychiatry Group, where this site refers patients, publishes its own steps. These are its words, read October 29, 2026:
- Call or send a request. Mention SPRAVATO so the office can plan the right evaluation.
- Psychiatric evaluation. The psychiatrist reviews your diagnosis, every antidepressant you have tried, your medical history, blood pressure and safety.
- Insurance approval. It may run through the medical or the pharmacy benefit. Labyrinth says it usually takes 1 to 4 weeks from the first call to the first treatment.
- Program enrollment. The office enrolls you in the SPRAVATO REMS.
- Treatment visits. Two visits a week in the first month, each with at least 2 hours of observation and a ride home.
- Review after four weeks. You and the psychiatrist decide together whether to continue.
Cost depends on the plan. Our SPRAVATO insurance coverage guide explains what Medicare pays and what to ask your insurer.
Printable
Questions to bring to the evaluation
Bring these questions. Write the answers down. Keep health details for the visit, not for a web form.
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- What is my diagnosis: treatment-resistant depression with anxiety, an anxiety disorder, or both?
- Does my history meet the label's use, or would SPRAVATO be off-label for me?
- Which antidepressant trials count as adequate in my history, and which do not?
- What other options fit anxious depression for me, such as medication changes or TMS?
- How will you measure both my depression and my anxiety during treatment?
- What happens if my anxiety gets worse during or after a session?
- Will insurance cover it under my medical or pharmacy benefit, and what approval is needed?
- Who do I call between visits if things get worse, and what is the after-hours number?
Other options
Common treatments for anxiety and depression
SPRAVATO is not a first treatment for anxiety. NIMH lists the usual ones for generalized anxiety disorder.
- Antidepressants. SSRIs and SNRIs treat depression and can also treat the symptoms of generalized anxiety. They may take several weeks to work.
- Anti-anxiety medicines. NIMH names benzodiazepines and buspirone.
- Psychotherapy. Cognitive behavioral therapy is commonly used for generalized anxiety, in person or by telehealth.
- TMS. Since August 2021, TMS has been FDA-cleared to reduce anxiety symptoms in some adults with major depression. See our TMS for anxiety guide.
To weigh SPRAVATO against other next steps, read our TMS, SPRAVATO and ketamine comparison.
Common questions
SPRAVATO and anxiety: questions people ask
Does SPRAVATO help with anxiety?
There is no approval or anxiety-focused trial that shows it. What exists is a post hoc analysis of the main 4-week SPRAVATO trial: about 72 percent of patients had significant anxiety, and their depression scores fell more with SPRAVATO plus an oral antidepressant than with placebo plus an oral antidepressant. That analysis measured depression, not anxiety, and was written by the manufacturer's researchers.
Is SPRAVATO FDA-approved for anxiety?
No. The label approves SPRAVATO for treatment-resistant depression in adults, alone or with an oral antidepressant, and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior, with an oral antidepressant. No anxiety disorder is an approved use.
Can SPRAVATO make anxiety worse?
It can cause anxiety. In the treatment-resistant depression trials with an oral antidepressant, 13 percent of people on SPRAVATO reported anxiety, against 6 percent on placebo. Anxiety was also the most frequent side effect that led people to stop SPRAVATO across the phase 3 studies, at 1.2 percent. The Medication Guide asks patients to call their provider about new or worse anxiety or panic attacks.
Is esketamine used for generalized anxiety disorder?
Not as an approved treatment. A 2026 systematic review found 11 studies of ketamine, and none of esketamine, in people whose main diagnosis was an anxiety disorder. The ketamine studies varied widely in design and in how ketamine was given, and the review found that anxiety could return after maintenance treatment stopped.
Do anxiety and depression go together?
Often. In the large STAR*D study, 53.2 percent of patients starting antidepressant treatment had anxious depression. In the SPRAVATO trial analyzed for anxiety, about 72 percent of the patients with treatment-resistant depression had significant anxiety symptoms or an anxiety disorder.
How do I get SPRAVATO?
SPRAVATO is only given through an FDA-required safety program, the SPRAVATO REMS, in certified healthcare settings, after a prescriber decides it fits. The first step is a psychiatric evaluation. Labyrinth Psychiatry Group, where this site refers patients, says it usually takes 1 to 4 weeks from the first call to the first treatment, depending on the insurance company.
Does insurance cover SPRAVATO for anxiety?
SPRAVATO's approved uses are depression indications, and plans can require approval before the first treatment. Labyrinth notes it may be covered under the medical benefit or the pharmacy benefit, depending on the plan. Our SPRAVATO insurance coverage guide explains the codes and costs.
How do you feel on SPRAVATO?
In the label's treatment-resistant depression trials with an oral antidepressant, the most common effects were dissociation (41 percent), dizziness (29 percent) and nausea (28 percent). Every treatment session includes at least 2 hours of monitoring, until a clinician decides you are safe to leave. The label says no driving until the next day after a restful sleep.
Sources
What this page is built on
- SPRAVATO (esketamine) nasal spray, prescribing information and Medication Guide. Janssen Pharmaceuticals. DailyMed, SPL version 21, effective September 22, 2026.
- Daly EJ, Turkoz I, Salvadore G, and colleagues. The effect of esketamine in patients with treatment-resistant depression with and without comorbid anxiety symptoms or disorder. Depression and Anxiety. 2021;38(11):1120-1130. Authors include Janssen employees.
- Turkoz I, Nelson JC, Wilkinson ST, and colleagues. Predictors of response and remission in patients with treatment-resistant depression: a post hoc pooled analysis of two acute trials of esketamine nasal spray. Psychiatry Research. 2023;323:115165. Authors include Janssen employees.
- Masdrakis VG, Tebbs Z, Natsis V, Baldwin DS. Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: systematic review. Journal of Psychopharmacology. 2026;40(6):877-899.
- McIntyre RS, Kato M, Thase ME, and colleagues. Adjunctive pharmacotherapy for major depressive disorder with anxiety symptoms: from monoamines to recent clinical evidence. CNS Drugs. 2026;40(9):1185-1206. Funded by Otsuka and Lundbeck.
- Schiele MA, Fagan HA, Baldwin DS, Domschke K. Integrative systematic review on pharmacological, psychotherapeutic, and neurostimulatory treatment options in treatment-resistant anxiety disorders. Psychotherapy and Psychosomatics. 2026;95(3):214-247.
- Glue P, Medlicott NJ, Harland S, and colleagues. Ketamine's dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders. Journal of Psychopharmacology. 2017;31(10):1302-1305.
- Glue P, Neehoff SM, Medlicott NJ, and colleagues. Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disorders. Journal of Psychopharmacology. 2018;32(6):663-667.
- Fava M, Rush AJ, Alpert JE, and colleagues. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. American Journal of Psychiatry. 2008;165(3):342-351.
- Gaspersz R, Lamers F, Kent JM, and colleagues. Longitudinal predictive validity of the DSM-5 anxious distress specifier for clinical outcomes in a large cohort of patients with major depressive disorder. Journal of Clinical Psychiatry. 2017;78(2):207-213.
- National Institute of Mental Health: Generalized anxiety disorder (GAD): when worry gets out of control
- Labyrinth Psychiatry Group: SPRAVATO (esketamine) treatment, how to start (read October 29, 2026)
The label, study abstracts, NIMH page and Labyrinth's steps were read October 29, 2026. Trial numbers are group averages and do not predict any one person's result. This page does not recommend SPRAVATO or any other treatment for a particular person, and it does not replace the advice of the treating team.