What is Spravato Used For?
Spravato (intranasal esketamine) is FDA-approved for treating treatment-resistant depression (TRD) in adults—either as monotherapy or combined with an oral antidepressant—and for treating depressive symptoms in adults with major depressive disorder (MDD) who have acute suicidal ideation or behavior, always in conjunction with an oral antidepressant. 1
Primary Indications
Treatment-Resistant Depression (TRD)
Spravato is specifically reserved for patients with major depressive disorder who have failed at least 2 adequate trials of antidepressant medications 2. This is not a first-line treatment—it should only be considered after conventional antidepressants have proven ineffective or intolerable 2.
The 2022 VA/DoD Clinical Practice Guidelines represent a significant shift, now recommending ketamine or esketamine as a treatment option for patients who have not responded to several adequate pharmacologic trials, whereas the 2016 guideline recommended against ketamine use outside research settings 2.
Major Depressive Disorder with Acute Suicidal Ideation or Behavior
Spravato is approved for treating depressive symptoms in adults with MDD who present with acute suicidal ideation or behavior, used alongside an oral antidepressant 2, 1.
Critical Limitations You Must Know
The effectiveness of esketamine in preventing suicide or reducing suicidal ideation or behavior has NOT been established 2, 1. This is a crucial distinction—while approved for this indication, it should not be relied upon as a suicide prevention strategy.
Use of Spravato does not eliminate the need for hospitalization if clinically warranted, even if patients show improvement after the initial dose 1.
Spravato is NOT approved as an anesthetic agent, and its safety and effectiveness as anesthesia have not been established 1.
How It Works and Why It's Different
Spravato is a non-competitive NMDA receptor antagonist that provides rapid antidepressant effects—often within 24 hours of administration 2. Meta-analysis data shows that twice-weekly esketamine as augmentation to ongoing oral antidepressants improved depressive symptoms and remission rates in patients with TRD at up to 28 days of follow-up 2.
Real-world effectiveness studies confirm these findings, with one analysis showing moderate to severe baseline depression symptoms reduced to the mild range after 4 weeks, sustained over 16 weeks of treatment 3.
Administration Requirements and Safety Monitoring
Spravato can ONLY be administered through a restricted REMS (Risk Evaluation and Mitigation Strategy) program due to risks of sedation, dissociation, respiratory depression, and potential for abuse 2, 1. This means:
- Must be given under direct healthcare provider supervision in certified healthcare settings
- Requires mandatory 2-hour post-administration monitoring period
- Pharmacy and healthcare setting must be REMS-certified
- Patients in outpatient settings must be enrolled in the REMS program 2, 1
Specific Monitoring Requirements:
- Respiratory status monitoring (including pulse oximetry) for at least 2 hours at each session 1
- Blood pressure assessment before dosing and at approximately 40 minutes post-dose (corresponding to peak concentration) 1
- Patient cannot leave until clinically stable, as determined by healthcare provider assessment 1
Common Pitfalls to Avoid
Do not use as first-line treatment: Esketamine is explicitly reserved for patients who have failed previous therapies 2
Do not administer if baseline blood pressure is significantly elevated (>140 mmHg systolic, >90 mmHg diastolic) without careful risk-benefit assessment 1
Contraindicated in patients with: aneurysmal vascular disease, arteriovenous malformation, or history of brain bleeding 1
Food and liquid restrictions: Patients should avoid food for at least 2 hours before administration and liquids for at least 30 minutes prior, due to risk of nausea and vomiting 1
Timing with nasal medications: If patients require nasal corticosteroids or decongestants, these must be administered at least 1 hour before Spravato 1
Evidence Quality and Real-World Effectiveness
While long-term efficacy and safety data remain limited 2, emerging real-world studies support its effectiveness. A Spanish observational study (INTEGRATE) found 80.4% of patients in response or remission during induction phase, with 28% experiencing improvement within 24 hours of first administration 4. Another real-world analysis showed sustained effectiveness over 16 weeks with generally mild, transient adverse effects 3.
The most common adverse effects are dissociation and sedation, which are typically transient and decrease over time, particularly during the first 4 weeks 4.