Spravato (Esketamine) Treatment Criteria & Clinical Uses FDA-Approved (On-Label) Indications Spravato is FDA-approved for use in conjunction with an oral antidepressant in the following situations: Treatment-Resistant Depression (TRD): Defined as failure of at least two different antidepressant medications of adequate dose and duration in the current depressive episode. Patient must be currently experiencing moderate to severe Major Depressive Disorder (MDD). Major Depressive Disorder with Acute Suicidal Ideation or Behavior: Used for rapid reduction of depressive symptoms in patients with active suicidal thoughts or behaviors. Requires concurrent initiation or continuation of oral antidepressant therapy. General Eligibility Criteria To qualify for Spravato treatment, a patient must meet the following: Diagnosis of MDD with TRD or acute suicidality. Failure of at least two oral antidepressants in the current episode (for TRD). 18 years of age or older. No history of psychotic disorders, including schizophrenia. No active substance use disorder, particularly with stimulants or alcohol. No uncontrolled hypertension or cardiovascular instability. Must be able to attend in-clinic administration sessions twice weekly initially. Must be enrolled in the REMS (Risk Evaluation and Mitigation Strategy) program. Must have adequate social or transportation support due to the 2-hour post-administration monitoring requirement. Off-Label Uses (Emerging or Investigational) Spravato and racemic ketamine (IV/IM formulations) are being used or studied off-label in the following conditions: Post-Traumatic Stress Disorder (PTSD): Particularly in complex PTSD or refractory cases. Some evidence for rapid symptom relief in suicidal ideation and dissociative symptoms. Bipolar Depression (with caution): Used cautiously in bipolar depression not responsive to standard treatments. Not for patients with active mania or mixed episodes. Obsessive-Compulsive Disorder (OCD): Under investigation, based on its rapid-acting glutamate modulation. Chronic Suicidality: Beyond MDD context, some clinics utilize Spravato as a maintenance treatment for patients with repeated suicidal crises. Severe Anxiety Disorders (e.g., GAD, Panic Disorder): Anecdotal or emerging evidence for benefit in refractory cases. Substance Use Disorders: Intranasal or IV ketamine is under study for alcohol and cocaine dependence, due to neuroplasticity and craving modulation effects. Pain Management (rare with Spravato, more with IV ketamine): Conditions such as neuropathic pain, CRPS (Complex Regional Pain Syndrome) — usually managed with IV ketamine, not Spravato. Contraindications: History of aneurysmal vascular disease, including intracranial, thoracic, or abdominal aorta, or arteriovenous malformation. History of intracerebral hemorrhage. Uncontrolled hypertension. Pregnancy and breastfeeding (risk not well established). Monitoring Requirements: Vital signs before and after administration. Two-hour observation period post-dose. BP monitoring post-dose due to risk of transient elevation. Assessment for dissociation, sedation, and psychotomimetic effects. Ongoing mood and suicidality monitoring using standardized scales (e.g., PHQ-9, MADRS).