Spravato - Coverage, REMS, Billing, and Operational Tips
Access to IV ketamine therapy is limited by high patient costs, lack of coverage, and other regulatory hurdles.
Spravato (esketamine), an FDA-approved option, offers hope for those struggling with treatment-resistant depression (TRD) or major depression with acute suicidal thoughts (MDSI).
Unlike IV ketamine, Spravato is covered by almost all insurance plans and follows strict safety protocols (REMS).
It’s a practical alternative for those in need.
Define Your Why
However, obtaining SPRAVATO and managing its REMS program can be quite complex for clinics and providers.
So why go through all that trouble?
SPRAVATO creates a unique experience for providers and patients—
Time
How often does a provider spend 2 hours with their patient twice a week for 4 weeks?
This duration and frequency of treatment allow providers and patients to build strong relationship and trust.
2. Autonomy
a. Patients
SPRAVATO is self-administered, allowing patients to take an active role in their treatment.
By learning the correct techniques and administering Spravato at their own pace, they often feel a sense of autonomy and responsibility for their care.
TIP - During the initial assessment, show patients their treatment room and provide training sprays for them to practice with.
b. Providers
There are no rigid guidelines for the setup of Spravato therapy sessions.
This allows providers to bring their own personal style into the practice space.
They have full control over the choice of art, music, aroma, lighting, and integrative methods to maximize treatment outcome.
Flexible treatment settings give providers the opportunity to be more involved and engaged in the treatment process.
TIP - Before treatment, offer patients the option to choose their treatment room (if available).
This can help enhance their sense of autonomy.
3. The Pyschedelic Magic
Rarely do you see a patient walk into a clinic sick and walk out with drastic improvement.
Spravato’s rapid, robust antidepressant effects are highly rewarding for many healthcare providers.
Unpacking the Purpose
Collectively increasing the number of clinics that offer Spravato in a legal, safe, and knowledgeable manner can expand access to this valuable treatment for those who need it most.
Since the FDA and payers are dragging their feet on Ketamine, let’s work with what’s available and make ketamine therapy a real option for those needing new paths to heal.
In this blog, we’ll break down who qualifies, how dosing works, safety standards like REMS, side effect profile and management, and how to create a supportive environment for patients.
We’ll also walk through insurance options, the prior authorization process, billing tips, follow-up care, and ways clinics can improve the patient experience while staying compliant.
We can choose to offer real relief for those who’ve felt like they’ve run out of options.
Let’s get started.
Spravato (Esketamine) Guidelines for Treatment
1. Indications and Usage
SPRAVATO® is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist nasal spray approved for use in adults for—
Treatment-Resistant Depression (TRD)
Administered in conjunction with an oral antidepressant for adults who have not responded adequately to at least two antidepressant treatments.
Depressive Symptoms in MDD with Acute Suicidal Ideation/Behavior (MDSI)
Also used in conjunction with an oral antidepressant for rapid reduction of depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior.
It does not replace the need for hospitalization in individuals at immediate risk of suicide.
2. Dosing Protocols
Treatment-Resistant Depression (TRD)
Induction Phase (Weeks 1-4)
Day 1 Starting Dose: 56 mg.
Subsequent Doses: 56 or 84 mg twice weekly, depending on patient tolerance and response.
Maintenance Phase (Weeks 5-8)
Administer 56 or 84 mg once weekly.
Continuation Phase (Week 9 and beyond)
Administer 56 or 84 mg every two weeks or once weekly based on patient response.
Depressive Symptoms in MDD with Acute Suicidal Ideation/Behavior (MDSI)
Induction Phase (4 weeks)
84 mg twice weekly for four weeks.
56 mg dose may be considered for patients with tolerability concerns.
No Maintenance or Continuation Phase
3. Patient Selection Criteria
Eligible Patients
Adults diagnosed with TRD who have failed at least two antidepressant trials.
and/or
Adults with MDD and acute suicidal ideation needing rapid symptom relief, though long-term efficacy for preventing suicide has not been demonstrated.
Exclusion Criteria
Hypersensitivity to esketamine or ketamine
Cardiovascular Conditions
Uncontrolled hypertension
Adults (18 - 64 years)
BP should be < 140/90 mmHg prior to treatment
Older Adults (≥ 65 years)
< 150/90 mmHg
Aneurysmal vascular disease (e.g., thoracic or abdominal aortic aneurysms, arteriovenous malformations)
History of intracerebral hemorrhage
Special Considerations (Risk-benefit analysis)
Severe pulmonary insufficiency, such as COPD
Uncontrolled arrhythmias (bradycardia or tachycardia) causing hemodynamic instability
History of myocardial infarction, especially if recent (< 1 year)
Hemodynamically significant heart conditions, like severe valvular heart disease or heart failure (NYHA Class III-IV).
Active medications that “may cause sedation or blood pressure changes” (REMS reporting requirement).
Benzodiazepines
Non-benzodiazepine sedative hypnotics
Psychostimulants
Monoamine oxidase inhibitors (MAOIs)
Psychiatric Disorders
Current or past Psychotic disorders (i.e. schizophrenia) should be excluded.
Substance Use Disorders
Active substance misuse or a history of ketamine or esketamine abuse.
Pregnancy and Breastfeeding
SPRAVATO may cause fetal harm and is not recommended in pregnant or breastfeeding women.
Hepatic Impairment
Patients with severe hepatic impairment (Child-Pugh Class C) should not receive SPRAVATO.
Neurological Conditions
Exclude patients with intracranial lesions, increased intracranial pressure, or a history of traumatic brain injury.
4. Administration and Treatment Setting
Prescriber must be onsite during SPRAVATO administration and monitoring (REMS requirement).
The prescriber is not required to be directly involved in the administration or monitoring process, though it is recommended.
Administration Route
Intranasal administration is the only approved method.
Patients self-administer 56 mg (2 devices) or 84 mg (3 devices) in the supervision of a “healthcare provider”.
A 5-minute rest between devices is mandatory to allow proper absorption.
Make sure tissues are readily accessible.
Clinical Setting
SPRAVATO must be administered in a certified healthcare facility enrolled in the REMS program.
Post-administration observation
Monitor patients for a minimum of 2 hours after dosing for potential adverse effects (REMS Requirement).
Must be done by a “healthcare provider”
Does not specify direct monitoring
Some providers use baby monitors with a call button for patients to request assistance when needed.
Sedation, dissociation, and blood pressure.
Blood pressure should be measured and recorded
Before treatment,
40 minutes after dosing, and
Before discharge
If blood pressure remains elevated, further observation or intervention by a healthcare provider trained in blood pressure management is required.
Continuous pulse oximetry is recommended during treatment.
Other REMS Requirement
“I confirmed that vital signs (BP, HR, RR) were in an acceptable range prior to..”
SPRAVATO Administration
Patient discharge
Remember, patients might need a bathroom break.
Assist them when standing up or sitting down, as Spravato commonly causes dizziness and sedation.
5. Safety Protocols and Side Effect Management
Common Adverse Reactions
Sedation (50%-61%)
Patient has to be assessed for sedation and cleared prior to discharge
Patients should not drive or operate heavy machinery until the following day after a restful sleep.
Dissociation (61%-84%)
Patient has to be assessed for dissociation and cleared prior to discharge
Perceptual disturbances and time distortion
Usually transient but require close monitoring.
Use of standardized assessments like the Clinician-Administered Dissociative States Scale (CADSS) is recommended.
Blood Pressure Increases
Monitor for blood pressure spikes (commonly occurring 40 minutes post-dose).
Healthcare providers must be prepared to manage hypertensive crises with immediate medical intervention if symptoms like chest pain or headaches occur.
8% of patients experience SYSTOLIC BP increases ≥40 mmHg (systolic)
19% of patients experience DIASTOLIC BP increases ≥25 mmHg (diastolic)
Hypertensive episodes can occur, particularly in patients with underlying cardiovascular conditions.
Serious Risks
Hypertensive Crisis
Blood pressure increases are common and transient.
Consider treatment if prolonged elevation (> 90 mins post administration)
If hypertensive encephalopathy occurs (e.g., severe headache, seizures, altered consciousness), patients must be referred to emergency care.
Abuse and Misuse
SPRAVATO is a Schedule III controlled substance.
Evaluation is important during the initial assessment and after induction, especially for spotting drug-seeking behaviors or frequent requests for more doses.
6. Clinician Training and Certification
Certified Healthcare Providers
Only healthcare professionals trained and certified under the SPRAVATO REMS program can administer SPRAVATO.
The REMS program ensures that all patients are monitored appropriately during and after the administration of the medication.
Emergency Response Preparedness
Healthcare providers must be trained to manage potential cardiovascular emergencies, including hypertensive crises, and sedation-related respiratory depression.
ACLS requirement isn’t explicitly stated
General recommendation is to have at least one certified provider on-site during treatment.
7. Long-Term Efficacy and Follow-Up Care
After 4 weeks of treatment, clinical benefit should be assessed to determine whether continued treatment is appropriate.
For TRD, the efficacy of SPRAVATO should be evaluated after each phase.
Spravato is typically not recommended beyond 4 weeks for MDSI.
Ongoing Monitoring
Blood Pressure and Cognitive Assessments
Regular monitoring of blood pressure and cognitive function is recommended during follow-up appointments.
Symptom Tracking
Use validated symptom rating scales like the Montgomery-Åsberg Depression Rating Scale (MADRS) to monitor depressive symptoms.
Long-Term Risks
Patients should be followed up regularly to assess for cognitive decline, urinary symptoms, and signs of dependence.
8. Clinical Data Overview (Package Insert & Clinical Studies)
Efficacy Data
Patients with TRD who received Spravato in combination with an oral antidepressant experienced a improvement in depressive symptoms compared to placebo + oral AD.
As discussed in our previous blog post, only two phase III trials resulted in statistical significance (TRANSFORM-2 for short-term and SUSTAIN-1 for long-term)
In patients with MDD and suicidal ideation, Spravato demonstrated rapid symptom reduction, though long-term data on suicide prevention is still inconclusive.
Adverse Event Data
Sedation (48-61%)
Typically occurs within 40 minutes post-dose (Cmax) and resolves within 2 to 3 hours.
Dissociation (61-84%)
Symptoms often peak around 40 min but typically resolve within the observation period.
Significant BP elevation
Definition
Systolic elevation ≥ 40 mmHg (8%), and/or
Diastolic elevation ≥ 25 mmHg (13%)
3-4% experienced systolic blood pressure elevations above 180 mmHg
Transient but significant
9. Practical Recommendations for Enhancing Spravato (Esketamine) Therapy
This section outlines practical recommendations designed to help healthcare providers optimize patient care during Spravato (Esketamine) administration.
These recommendations go beyond the package insert and address common clinical challenges while ensuring patient safety and effective management of adverse events.
a. Blood Pressure Management
Expected Blood Pressure Increases
At 40 minutes post-dose, patients receiving Spravato with an oral antidepressant saw average systolic blood pressure increases of 8-19 mmHg and diastolic increases up to 9.5 mmHg.
In the TRD clinical studies, unless clinically indicated, it was recommended that transient increases in BP not be treated.
Rationale
The BP typically returns to pre-dose values within 2 hours following SPRAVATO administration.
The effect of any treatment may result in hypotension.
At 1.5 hours post-dose, the mean elevation reduced to 2-5 mmHg in SBP and 1-3 mmHg in DBP.
Management of Hypertension
Mild to moderate BP elevation is normal and transient.
Consider treatment delay if BP > 140/90 mmHg (Package Insert)
If elevated prior to treatment, recommend breathing exercises (i.e. 4-7-8 breathing) and remeasure in 15 minutes.
Expect BP to peak around 40 minutes (REMS monitoring requirement)
If IV treatment (i.e. IV Labetalol) is not available…
Captopril
Oral ACE-I
Lowers BP within 30 minutes
Watch for hyperkalemia and angioedema.
Clonidine
Oral α2A-adrenergic agonist
Lowers BP in 15-30 minutes
Can cause sedation, dry mouth, and rebound hypertension.
Labetalol
Oral/IV non-selective beta + selective alpha-1 adrenergic antagonist
Avoid in heart block, bradycardia, or bronchospastic disease.
When to Seek Emergency Care
Refer patients immediately for emergency care if experiencing symptoms of…
Hypertensive crisis (e.g., chest pain, shortness of breath), or
Hypertensive encephalopathy (e.g., sudden severe headache, visual disturbances, seizures, diminished consciousness or focal neurological deficits)
BP >180/110 mmHg without clinical presentation of organ damage (i.e. abdominal pain, vision changes) does NOT always warrant urgent intervention.
Practical recommendations
BP should peak around 40 minutes and trend down to baseline
Have BP management protocol (questionnaire to assess organ damage, med selection, monitoring, follow-up, etc.)
b. Managing Psychiatric Events in Outpatient Settings
Distress or Anxiety can emerge, particularly common with dissociation.
Cluster B patients may be more prone to these adverse events
Ask patients to avoid violent or graphic content consumption (i.e. horror films or games) days leading up to treatment.
Practical Management
Provide in-person companionship.
Speak in a slow and composed manner.
For outpatient settings, oral lorazepam (1–2 mg) may be a practical option for managing excessive distress or anxiety without requiring IV administration.
Dissociation Management
Per Janssen, dissociation occurs more frequently in people with a history of…
Post-traumatic stress disorder (PTSD)
Childhood maltreatment or traumatic events
Eating disorders
Substance abuse (including alcohol)
Alexithymia (inability to identify and describe emotions)
Anxiety and mood disorders
Suicidality
Encourage the use of grounding techniques such as guided imagery or deep breathing to help patients feel more connected during episodes of dissociation.
c. Managing Concomitant CNS Depressants (e.g., Benzodiazepines and Opioids)
Benzodiazepines
Patients on benzodiazepines should be monitored closely for excessive sedation during Spravato treatment.
Consider reducing the benzodiazepine dose or pausing the medication for 12 hours before treatment to minimize the risk of compounded sedation.
Opioids
For patients on opioids, extra caution is warranted to avoid respiratory depression.
Reduce opioid doses before treatment or ensure close monitoring of respiratory function during treatment.
d. Pregnancy and Contraception Considerations
Pregnancy Testing
Ensure that ALL patients of childbearing potential undergo pregnancy testing before starting treatment.
Contraception
Patients should be advised to use effective contraception during treatment and for at least one month after the last dose.
Breastfeeding should be avoided due to the potential for neurotoxicity to infants.*
* Due to ketamine’s rapid metabolism, a large volume of distribution (9.8 L/kg), and low oral bioavailability, significant exposure after a terminal half-life of 7-12 hours is unlikely. However, some ketamine metabolites have been shown to impact neurochemistry. Due to limited data, it’s not possible to conclude esketamine’s safety in this population.
e. Cognitive Impairment and Driving Restrictions
Cognitive Impairment
Many patients experience cognitive decline post-treatment, including slower reaction times and impaired judgment.
Driving Restrictions
Patients should be instructed not to drive or operate heavy machinery until the day after their treatment and after a full night’s sleep.
Ensure that patients arrange for transportation to and from the clinic on treatment days.
f. Nausea and Vomiting Prevention
Prevalence
Nausea and vomiting occur in 28-32% of patients, especially during early treatment sessions.
Preventive Measures
Instruct patients to avoid food for at least 2 hours before treatment and liquids for 30 minutes before the session to minimize nausea.
Ondansetron (Zofran) can be prescribed pre/post treatment if necessary.
Some clinics report Zofran as the most utilized PRN meds in SPRAVATO treatments.
Make sure to go over the patient's med list and remind them the NPO rules do not apply to their regular medications (especially HTN meds).
Non-Pharmacologic Strategies
Encourage breathing exercises or acupressure on the P6 acupoint (located on the wrist) to alleviate nausea.
Have mints available as the taste of dripped medicine are unpleasant (may help with mild nausea as well)
g. Nasal Medications and Timing
Nasal Decongestants or Corticosteroids
Nasal decongestants or corticosteroids should not be taken less than 1 hour before Spravato to avoid absorption interference (Package Insert).
h. Creating a Therapeutic Environment
Mindfulness and Relaxation
Patients can benefit from engaging in mindfulness exercises prior to and during treatment.
Providing soothing music or guided meditation recordings can help create a relaxing environment and reduce anxiety.
Physical Environment
The treatment room should have dim lighting, comfortable seating, and a quiet atmosphere to reduce sensory overstimulation during administration.
Breathing Exercises
Encourage patients to practice deep breathing techniques during their session to promote relaxation and reduce dissociative feelings.
Consider patient-specific settings
If you have access to more than two treatment rooms, you could design distinct environments to suit different patient preferences.
For instance, one room might feature a beach theme with ocean sounds, while the other could be tailored for patients who prefer a mountain setting.
You might want to use smart light bulbs to offer more flexibility in adjusting the color settings.
Navigating the SPRAVATO® REMS: A Guide for Healthcare Providers
Becoming REMS-certified is essential for healthcare settings that want to administer SPRAVATO® (esketamine) CIII Nasal Spray to appropriate patients.
Below is a step-by-step guide based on the provided source material, covering everything from the initial enrollment process to ongoing compliance requirements.
Why SPRAVATO® requires REMS
The SPRAVATO® REMS program exists because of the medication's potential risks, including sedation, dissociation, cardiovascular issues, and the possibility of abuse and misuse.
To mitigate these risks and ensure patient safety, the FDA mandates that healthcare settings and pharmacies meet specific requirements before administering or dispensing SPRAVATO®.
Step 1: Initial Steps Toward REMS Certification
Identify Your Healthcare Setting Type
Before starting the certification process, determine whether your setting is classified as "inpatient" (hospitals, emergency departments) or "outpatient" (outpatient medical offices and clinics).
This distinction will determine which enrollment forms you use and the specific requirements you'll need to meet.
Designate an Authorized Representative
Select an individual within your healthcare setting who will be responsible for overseeing compliance with the SPRAVATO® REMS requirements.
This individual will be the point of contact for REMS-related matters.
Step 2: Choosing Your Acquisition Pathway
Buy-and-Bill
The buy-and-bill model involves purchasing SPRAVATO® directly from a REMS-certified specialty distributor.
Your facility would then bill the payer for both the medication and any associated services.
This pathway is generally covered under the medical benefit.
Specialty Pharmacy
Alternatively, you can choose to obtain SPRAVATO® through a REMS-certified specialty pharmacy.
With this method, you send a prescription to the pharmacy.
The pharmacy will initiate the prior authorization, obtain the medication, and deliver it directly to your clinic for administration.
The pharmacy bills the drug benefit for reimbursement.
Providers can bill the medical benefit for the administration and monitoring services.
It's important to note that you can opt for either one or both of these acquisition pathways, depending on your needs and your patients' insurance plans.
Step 3: Completing the REMS Enrollment
Once you've identified your setting type and chosen an acquisition pathway, you'll need to complete the appropriate REMS enrollment form.
Outpatient Settings
Complete and submit the "Outpatient Healthcare Setting Enrollment Form".
Inpatient Settings
Complete and submit the "Inpatient Healthcare Setting Enrollment Form".
These forms can be submitted online at www.SPRAVATOrems.com or faxed to the SPRAVATO® REMS at 1-877-778-0091.
TIP
Common reasons for delays in REMS enrollment include incomplete or incorrect information on these forms (i.e. clinic address, signature, dates).
Step 4: The Know Your Customer (KYC) Questionnaire (Buy-and-Bill Only)
If you've opted for the buy-and-bill pathway for acquiring SPRAVATO®, complete the Janssen Know Your Customer (KYC) Questionnaire.
When you select the buy-and-bill option on your REMS enrollment form, you'll receive an email containing the KYC Questionnaire from the SPRAVATO® REMS Administrator.
Why is the KYC Questionnaire Necessary?
SPRAVATO® contains esketamine, a Schedule III controlled substance.
The KYC Questionnaire helps Janssen understand your healthcare setting's current practices for handling controlled substances.
Gather essential DEA and licensing information to ensure compliance.
Step 5: Connect with an Authorized Specialty Distributor (Buy-and-Bill Only)
After you've been approved for the buy-and-bill pathway, you can establish an account with a SPRAVATO® Authorized Specialty Distributor (SD).
Be prepared to provide information such as your DEA certifications, business background, credit references, and potentially undergo credit and background checks.
TIP
Be sure to reach out to all distributors for price comparisons (Besse Medical, Cardinal Helath, and CuraScript).
Some clinics report that Besse Medical offers the lowest prices.
Step 6: Maintaining Compliance with SPRAVATO® REMS
Becoming REMS-certified is an ongoing process, requiring diligence in upholding the program's safety standards.
Here's what you need to do to maintain compliance.
Ongoing Staff Training
Provide continuous training to all staff members involved in prescribing, dispensing, and administering SPRAVATO®.
Training should cover the medication's risks, proper administration techniques, monitoring protocols, and REMS program requirements.
Patient Enrollment (Outpatient Settings Only)
In outpatient settings, you must enroll every patient in the SPRAVATO® REMS program before their first treatment session.
This is done by completing the Patient Enrollment Form.
Patient Monitoring (Outpatient Settings Only)
After each SPRAVATO® treatment session in an outpatient setting, you must complete a Patient Monitoring Form and submit it to the REMS within 7 days.
This form documents information about the administered dose, required monitoring values, and any adverse events.
DOCUMENTATION
Maintaining clear records can save time and reduce headaches.
Keep comprehensive records of staff training, SPRAVATO® shipments received, patient dispensing information, and completed Patient Monitoring Forms.
Onsite REMS Requirements
Have a prescriber onsite during SPRAVATO administration and monitoring.
Ensure healthcare provider(s) are supervising administration and monitoring patients.
Authorized Representative Responsibilities
Designate an authorized representative to
Oversee the certification process and compliance with the REMS Program.
Review the SPRAVATO prescribing information.
Help patients enroll in the REMS Program.
Ensure compliance with audits carried out by Janssen Pharmaceuticals, Inc.
Janssen typically audits 10% of all health care settings (annual).
If the authorized representative changes at any time, the clinic is required to re-certify with a new authorized representative.
Staff Training
Train relevant staff on…
Patient self-administration under the supervision of a healthcare provider.
Monitoring for resolution of sedation, dissociation, and changes in vital signs for at least 2 hours post-administration.
Establish processes to identify and train new staff involved in prescribing, dispensing, and administering SPRAVATO.
Table 1. SPRAVATO® Treatment Guidelines Summary
| Category | Details |
|---|---|
| Indications and Usage |
TRD In combination with an oral antidepressant for adults who failed at least 2 antidepressants. MDSI Rapid symptom relief; does not replace hospitalization for immediate suicide risk. |
| Dosing Protocols |
TRD - Induction (Weeks 1-4): Day 1: 56 mg; Twice weekly: 56 mg or 84 mg. - Maintenance (Weeks 5-8): Once weekly: 56 mg or 84 mg. - Continuation (Week 9+): Every 2 weeks or once weekly: 56 mg or 84 mg. MDD with Suicidal Ideation - 84 mg twice weekly for 4 weeks. |
| Patient Selection |
Eligibility - Adults with TRD or MDD with acute suicidal ideation. Exclusion - Cardiovascular: Uncontrolled hypertension, aneurysmal vascular disease, intracranial hemorrhage. - Hold treatment if resting BP >140/80 mmHG. - Other: Pregnancy, breastfeeding, active substance abuse, psychotic disorders, severe hepatic impairment. |
| Administration and Setting |
Route - Intranasal (56 mg or 84 mg per session). Healthcare Setting - Administered in certified clinics under REMS with 2-hour post-dose observation. Post-Administration Monitoring - Vital signs monitored pre-dose, 40 minutes post-dose, and pre-discharge. - Continuous monitoring for sedation, dissociation, and hypertensive events. |
| Clinician Requirements |
REMS Certification - Providers and clinics must be certified. Training - Clinicians must be trained in managing sedation, dissociation, and hypertensive emergencies (ACLS recommended). |
| Long-Term Efficacy and Follow-Up Care |
Follow-Up - Regular assessments using validated scales (e.g., MADRS). Long-Term Monitoring - Check for cognitive decline, urinary symptoms, and dependence. |
Table 2. SPRAVATO REMS Monitoring and Treatment Checklist
| Stage | Required Information |
|---|---|
| Before Treatment |
Patient Info: Name, DOB, Sex. Medications: Benzodiazepines, sedatives, psychostimulants, MAOIs. Counseling: Risks of sedation, dissociation, BP changes. Safe transportation required. Enrollment: Ensure patients are enrolled in the REMS program (outpatient). Vital Signs: BP and HR must be in acceptable range. |
| During Treatment |
Supervision: Patient self-administers under direct observation. Dose & Lot: Record dose (56 mg or 84 mg) and lot number. Vital Signs: BP check at 40 minutes post-dose and monitor for increases. Symptom Monitoring: Track onset of sedation/dissociation, provide meds if needed. |
| After Treatment (Monitoring) |
Observation: Monitor for at least 2 hours until sedation, dissociation, and BP stabilize. Final BP Check: Recheck BP before discharge. Form Submission: Submit monitoring form within 7 days. |
| Adverse Event Reporting |
Serious Events: Report SAEs (hospitalization, disability, life-threatening events) to Janssen and FDA. Non-Serious Events: Report any non-serious adverse events. |
Step-by-Step Guide to Spravato Coverage and Billing
1. Initial Considerations: In-Network vs. Out-of-Network
When deciding whether to provide Spravato in your practice, you must choose whether to be in-Network or out-of-Network with insurers.
This decision impacts reimbursement rates, the ease of prior authorizations, and patient costs.
Both options require prior authorization.
In-Network
Higher Chances for Approval
Insurers are more likely to approve prior authorizations for in-network providers.
Fixed Reimbursement Rates
The insurance company’s contracted rates are usually lower than out-of-network
Limited profit margins but offering more predictable reimbursements.
Smoother Billing Process
Insurance companies have established relationships with in-network providers, leading to a more straightforward billing process.
Out-of-Network
Risk of Denials
Insurers may reject prior authorization requests, especially if there’s an in-network provider within a certain radius (e.g., 30 miles).
Patient Responsibility
Patients may face higher out-of-pocket costs or full responsibility for the treatment cost if you are out-of-network.
Unpredictable Reimbursement
Out-of-network billing is riskier because reimbursement is rare or inconsistent.
TIP
Consult case managers (SPRAVATO withMe) FIRST for patient coverage options and covered billing codes.
They cannot submit any claims for you, but they often are very knowledgeable and prompt.
For state-specific PA info, visit Spravato Policy Acumen to gain access to comprehensive documents outlining PA coverage information.
2. Deciding Between Pharmacy Benefit vs. Buy-and-Bill
Similar to acquisition, Spravato offers two billing options—
Pharmacy Benefit and Buy-and-Bill.
Each method has its own advantages and disadvantages in terms of cash flow, logistics, and risk management.
The choice between the two is generally made by the payer.
For personalized coverage information, you can consult with Spravato's case management personnel (SPRAVATO withMe) free of charge, avoiding the need to navigate insurance companies directly.
Pharmacy Benefit
How it Works
The patient’s pharmacy delivers the medication to your clinic, and the insurance company bills the pharmacy benefit.
No Upfront Costs
The practice does not pay for the medication, lowering the financial burden.
Strict Timelines
The medication is patient-specific and must be used within a two-week (14-day) window.
It cannot be reused for other patients, even if it goes unused.
SPRAVATO® Disposal Program: 888-912-7348.
Fewer Logistics
You don’t need to maintain inventory or secure storage for Spravato on-site.
Buy-and-Bill
How it Works
Your clinic purchases Spravato from a distributor and bills insurance for both the drug and administration.
Costs
The cost per 84 mg dose ranges from $700 to $900.
Some distributors (e.g., Besse Medical) are known to offer 90-day payment terms, giving time to receive reimbursement before paying for the medication.
Flexibility
The practice can use stock for multiple patients, offering more flexibility with scheduling.
Financial Risk
If a claim is denied, the practice bears the cost of the medication, making this option riskier.
Tip
Negotiate rates with distributors to reduce upfront costs and improve cash flow management.
As previously noted, some providers suggest Besse Medical to have the best price for Spravato (no affiliations to disclose).
Buy-and-bill gives your practice control over inventory and simplifies patient scheduling.
4. Billing for Spravato Treatment
Accurate coding is essential for both proper reimbursement and successful claims processing.
Start with the correct ICD-10-CM Diagnosis Codes and then apply the appropriate billing codes for Spravato treatments.
ICD-10-CM Diagnosis Codes for Consideration
Ironically, there is no ICD-10-CM code for TRD or MDSI..
Following ICD-10 codes are suggested by Janssen**
For Patients New to SPRAVATO
F32.0: Major depressive disorder, single episode, mild
F32.1: Major depressive disorder, single episode, moderate
F32.2: Major depressive disorder, single episode, severe without psychotic features
F32.9: Major depressive disorder, single episode, unspecified
F33.0: Major depressive disorder, recurrent, mild
F33.1: Major depressive disorder, recurrent, moderate
F33.2: Major depressive disorder, recurrent, severe without psychotic features
R45.851: Suicidal ideations
For Patients Already Receiving SPRAVATO
F32.4: Major depressive disorder, single episode, in partial remission
F32.5: Major depressive disorder, single episode, in full remission
F33.41: Major depressive disorder, recurrent, in partial remission
F33.42: Major depressive disorder, recurrent, in full remission
** These codes are for REFERENCE ONLY and must follow FDA-approved guidelines. Don’t abuse it. Don’t make stuff up.
Tip
Always confirm the diagnosis reporting requirements with the patient’s insurer.
Billing Codes
Correct billing codes ensure that you get reimbursed properly for both the drug and the treatment services.
Here are some essential billing codes—
Medicare Codes
G2082: For the 56 mg dose of Spravato
Use: This code includes both the medication cost and the administration.
G2083: For the 84 mg dose
This code also includes both the medication cost and the administration.
This is the more common code for ongoing treatment sessions.
Medicare DOES NOT allow for any additional codes to be submitted with this G-code.
Medicaid Codes
Often mirrors Medicare and uses the G2082 and G2083 codes
Coverage varies state by state.
Be sure to check state and payer specific guidelines to ensure proper reimbursement.
NM Medicaid Reimbursement Rate Change 2023
Buy-and-Bill
S0013: Use this code for buy-and-bill under commercial insurance plans.
Requirement
Always include the NDC (National Drug Code) when billing with this code.
NDC and unit information are often required for dual-eligible patients (covered by both Medicare and Medicaid) and most Medicaid patients.
For the 56 mg dosage, the NDC code is N450458-0028-02 and the unit is UN2.
For the 84 mg dosage, the NDC code is N450458-0028-03 and the unit is UN3.
Evaluation and Management (E/M) Codes
99202 - 99205
For the initial evaluation of a new patient undergoing Spravato treatment.
The final digit of the code is based on the complexity and time spent.
Usually completed on a separate day before starting Spravato therapy.
If provided on the same day, use modifier 25
99212 - 99215
For follow-up visits after the initial evaluation.
The final digit of the code is based on the complexity and time spent.
TIP
Make sure to provide thorough documentations if using higher complexity codes (i.e. 99205 or 99215).
Most insurances will NOT cover 96127 (Brief Behavioral Assessment– i.e. PHQ-9s) by psych providers because they consider it to be a part of a standard mental health visit.
Primary Care Providers may be able to get reimbursement for this code.
99417 (Prolonged Services)
Use this code for sessions that last beyond the standard evaluation time.
TIP
Combine 99205 (initial evaluation) OR 99215 (follow-ups) with 99417 for prolonged sessions.
Example: For a 2-hour session, use 99215 with 99417 x 4.
99358 and 99359 will only work for inpatient monitoring, not outpatient.
90785 (Interactive Complexity Code)
Used for complex cases where extra time and effort are needed to manage the patient’s treatment (e.g.,, Asking patient to bring a ride to the appointment).
This code can add $6-$13 per session.
It’s not much, but it adds up over time if used consistently.
Utilize NCCI’s Procedure-to-Procedure Lookup to see if a specific combination of codes will work or not.
NPs and PAs with Master's degrees often receive 85% of the reimbursement rate of medical doctors.
Can be higher for incident-to-billing with MD’s supervision (i.e. co-signature).
Utilize NCCI’s Procedure-to-Procedure Lookup to see if a specific combination of codes will work or not.
FYI - Historical Codes (NO LONGER ACTIVE)
99354 and 99355 used to be prolonged service add-on codes for longer therapy sessions.
These were paired with psychotherapy codes 90837 and 90847 to indicate sessions lasting at least 90 mins (individual therapy) or 80 mins (family or couples therapy).
These codes were DISCONTINUED by the American Medical Association (AMA) as of January 1, 2023, and are NO LONGER REIMBURSABLE for sessions after that date.
The replacement code for extended sessions is 99417.
Table 3. Summary of Coding and Billing Scenarios for Spravato Treatment in Physician Offices
| Payer | Benefit Type | Site of Care | Procurement | Activity | Potential Coding Options | Potential Applicable Add-on Codes |
|---|---|---|---|---|---|---|
| Non-Medicare | Medical | Physician Office | Buy and Bill | Drug + Service |
Drug: S0013 or J3490 Service (E/M Codes): New: 99202-99205; Existing: 99212-99215 |
Prolonged Clinical Staff Service: 99415, 99416 Prolonged Service: 99417, G2212 |
| Non-Medicare | Medical | Physician Office | Buy and Bill | Drug + Service | Drug + Service: G2082 or G2083 | Payer discretion |
| Non-Medicare | Pharmacy | Physician Office | Pharmacy | Service | Service (E/M Codes): 99202-99205; 99212-99215 |
Prolonged Clinical Staff Service: 99415, 99416 Prolonged Service: 99417, G2212 |
| Non-Medicare | Medical | Physician Office | Pharmacy via Assignment of Benefits (AOB) | Service | Service (E/M Codes): 99202-99205; 99212-99215 |
Prolonged Clinical Staff Service: 99415, 99416 Prolonged Service: 99417, G2212 |
| Medicare | Medical | Physician Office | Buy and Bill | Drug + Service | Drug + Service: G2082 or G2083 | N/A |
| Medicare | Pharmacy | Physician Office | Pharmacy | Service | Service (E/M Codes): 99202-99205; 99212-99215 |
Prolonged Clinical Staff Service: 99415, 99416 Prolonged Service: G2212 |
| Medicare | Medical | Physician Office | Pharmacy via Assignment of Benefits (AOB) | Service | Service (E/M Codes): 99202-99205; 99212-99215 |
Prolonged Clinical Staff Service: 99415, 99416 Prolonged Service: G2212 |
Place of Service (POS) Codes
The Place of Service (POS) code provides essential information about the setting of care and is required on all professional service claims (billed on CMS-1500).
It identifies the location where the provider had a face-to-face encounter with the patient.
Table 4. Place of Service (POS) Codes
| Code | Setting Name | Description |
|---|---|---|
| 11 | Office |
Function: Exams, diagnoses, treatments. Setting: Ambulatory basis. Exclusions: Hospitals, skilled nursing facilities, public health clinics. |
| 19 | Off Campus Outpatient Hospital |
Function: Diagnostic, therapeutic, rehabilitation services. Location: Off-campus. Patient Needs: Do not require hospitalization. |
| 22 | On Campus Outpatient Hospital |
Function: Diagnostic and therapeutic services. Location: Main campus of a hospital. Patient Needs: Outpatients. |
| 53 | Community Mental Health Center |
Services Offered: Outpatient services, emergency care, day treatment, psychosocial rehabilitation. Additional Roles: Screens patients for state mental health facility admissions, provides consultation and education. |
5. Challenges in Spravato Billing and Coverage
Spravato treatment comes with several insurance challenges, including delays in payment and denials for certain patient conditions.
Here’s how to address some of these challenges—
Common Denials and How to Overcome Them
Substance Use Denials
Insurers frequently deny patients with a recent history of substance use (i.e. within the past year).
If the patient has a documented history, ensure that you thoroughly document and submit evaluation and assessment of their current condition (i.e. risks vs. benefit analysis) and include monitoring measures to prevent misuse.
Diagnostic Exclusion
Again, some insurers exclude coverage for patients with primary diagnoses of bipolar disorder or PTSD.
In these cases, if the patient also suffers from Treatment-Resistant Depression, ensure that TRD is the primary diagnosis in the documentation to maximize the chances of approval.
Changing Insurance Plans Mid-Treatment
If a patient changes insurance providers in the middle of treatment (e.g., job change or new plan at the start of the year), their Spravato coverage may be disrupted.
TIP
During intake, ask patients about any potential changes to their insurance coverage.
If they anticipate a change, suggest they maintain continuity through COBRA or other temporary insurance options.
Evaluation and Planning of Reauthorization Process Through Patient Progress Monitoring
Some insurers limit coverage duration to only the first month of treatment.
Healthcare providers must provide evidence of positive response to treatment for reauthorization (usually for 6 to 12 months).
For example, New Mexico Western Sky Medicaid Plans require a 50% decrease in a patient's PHQ-9 score for recertification.
The majority of plans don't cover MDSI beyond the initial 4 weeks.
Credentialing and Revalidation
Ensure all providers in your clinic are properly credentialed and regularly updated with insurance providers.
If any credentialing lapses, your clinic may temporarily fall out of network, resulting in denied claims.
Medicare and Medicaid
Regularly update your credentials with Medicare and state Medicaid to avoid falling out of network
Generally revalidates every 5 years.
Special attention should be paid to details like address (most common issue) and tax ID information to avoid billing issues and ensure smooth re-credentialing.
6. Savings and Rebate Options for Spravato Therapy
SPRAVATO withMe Savings Program
Eligibility
Patients with commercial insurance (not Medicare or Medicaid).
Patient Costs
Patients may pay as little as $10 per treatment, with an annual savings cap of $8,150 (up to 3 devices/session).
Covered Expenses (via Rebate)
Cost of medication (Buy-and-Bill or Pharmacy Benefits)
Observation costs require a separate application (Observation Rebate Program).
Assignment of Benefits
With patient authorization, providers can submit claims directly for reimbursement.
Patients sign a Patient Assignment of Benefits form, authorizing providers to receive direct payments.
Providers can fax this form to 844-584-1453.
Steps to Enroll
Confirm patient eligibility.
Submit enrollment form through Janssen CarePath's portal or via fax.
Provide prescription details and insurance verification.
Observation Rebate Program
Eligibility
Commercially insured patients who need monitoring during Spravato treatment.
Rebate Amount
Up to $500 annually for observation services, covering costs beyond treatment.
Rebate submissions must occur within 270 days of service.
Provider’s Role
Help patients submit receipts and rebate forms for observation-related fees.
Medicare Part D Extra Help Subsidy
Eligibility
Medicare beneficiaries enrolled in Part D.
Coverage
Extra Help Subsidy reduces co-pays, premiums, and deductibles.
Spravato may be covered under Medicare Part D, but providers must check the formulary to ensure coverage.
Janssen Patient Assistance Program (PAP)
Eligibility
Uninsured or underinsured patients, or those facing significant financial hardship.
Income Limits (as of 09/25/24)
Household of 1 - $43,740
Household of 2 - $59,160
Household of 5 - $105,420
Free Medication
Eligible patients may receive Spravato at no cost for up to one year.
The program requires income verification and proof of financial hardship.
Patients with employer-sponsored or government insurance are also eligible, as long as their insurance does not fully cover Spravato costs.
Steps to Enroll
Collect documentation
Proof of income
Prescription details
Insurance cards
Complete the PAP application via MyJanssenCarePath.com or fax it to 833-742-0791(Spravato PAP Info).
Patient Access Network (PAN) Foundation
Eligibility
Patients must meet financial criteria (typically between 400-500% of the Federal Poverty Level).
Medicare-only requirement
Patients must spend more than 4% of their gross annual household income on prescription drugs to qualify for assistance
Coverage
Assists with co-pays, coinsurance, and deductibles for eligible patients.
Providers can guide patients in submitting applications via the PAN Foundation website.
Alternative Options
Refer patients out to receive IV Ketamine if there is no insurance coverage.
Clinics may offer income-based sliding scale fees to make infusion cash prices more affordable.
Use financial assistance programs or funds for psychedelic treatments (i.e. Thank You Life) or look into clinical trial options.
Provider’s Step-by-Step Checklist for Payment Assistance
Verify Insurance
Ensure the patient’s insurance covers Spravato and determine potential out-of-pocket costs.
Utilize local SPRAVATO withMe case managers to determine initial coverage.
Initiate Enrollment
Enroll the patient in SPRAVATO withMe via Janssen CarePath.
Confirm the patient's eligibility and required documents.
Submit Assignment of Benefits
Have the patient complete the Patient Assignment of Benefits form so the provider can bill directly.
Ensure forms are sent to the correct fax number (844-584-1453).
Track Annual Limits
Monitor the patient’s savings limits to avoid exceeding the annual cap (i.e. Commercial Plans - $8,150 for treatment, $500 for observation).
Apply for Additional Assistance
For patients with limited coverage or financial hardship, assist in applying for the PAP or Medicare Part D Extra Help program to minimize out-of-pocket costs
Operational Efficiency Tips
Stay up to date with changes in policies to avoid potential billing issues.
SPRAVATO for healthcare providers website offers comprehensive information and resources.
Consult with SpravatoWithMe Case Manager First
Free experts who are incentivized to help you get the meds covered.
Run Multiple treatments Simultaneously (if possible)
Financially, running multiple Spravato patients simultaneously can improve profitability.
If your clinic can handle multiple sessions at staggered times, you can optimize both patient care and your business.
Prioritize patient safety above all else (Never let them drive themselves home).
Avoid spreading yourself too thin.
Imagine a scenario where multiple patients under your care require immediate medical attention, such as elevated blood pressure, nausea, or anxiety.
Plan how many patients you can effectively treat at the same time.
Generally, it is recommended that medical professionals or providers manage no more than two patients simultaneously.
Infrastructure
Secure the necessary infrastructure, including a secure storage system for Spravato if using the buy-and-bill model.
DEA inspections are likely if you handle controlled substances, so compliance is key.
Don’t be afraid to reach out to DEA for guidance or site visit.
Proper disposal of used SPRAVATO® devices is essential.
Designed for patient administration under the supervision of a healthcare professional, used devices must be discarded as medical waste in accordance with local, state, and federal regulations pertaining to controlled substances.
In the event that treatment is discontinued after a single SPRAVATO® dose, the partially used or unused portion of the product should be disposed of through the SPRAVATO® Disposal Program (P: 888-912-7348).
If the product's expiration date has passed, contact the pharmacy or the distributor for an exchange.
Use local Spravato reps for additional support
Automation
Use EHR Systems
Using electronic health record (EHR) systems with Spravato-specific templates can simplify the intake, documentation, REMS Compliance and prior authorization processes.
Osmind is the only EHR with Spravato specific integrations (i.e. Automated REMS submission, patient outcomes tracking, Superbill automation, etc). Not sponsored.
Utilize technology (regulations and reimbursements may vary by state)
Baby Monitors
Smart Vital Sign Monitoring Devices
AI-guided Prior Authorization Workflow
Electronic inventory monitoring system
AI-Driven Automatic Questionnaire
Final Thoughts
What’s fascinating about Spravato Therapy is the real partnership you build with the patient, especially early on when you spend a lot of time together.
We have the freedom and time to customize everything—lighting, music, and treatment goals—to fit your style and their needs.
With honest communication and good intentions,
We give and receive autonomy in our treatment process.
Always fight for your patients.
You are responsible for their care. Not the payers.
References
American Heart Association News. (2023, July 7). It’s not just inspiration: Careful breathing can help your health. American Heart Association. Retrieved from https://www.heart.org/en/news/2023/07/07/its-not-just-inspiration-careful-breathing-can-help-your-health
Esketamine (SPRAVATO) Criteria for Use. (2022, February). Veterans Affairs Pharmacy Benefits Management Services. Retrieved from https://www.va.gov/formularyadvisor/DOC_PDF/CFU_Esketamine_SPRAVATO_FEB2022.pdf
CGS Medicare. (n.d.). Procedure-to-procedure edits lookup tool. CGS Medicare. Retrieved from https://www.cgsmedicare.com/medicare_dynamic/j15/ptpb/ptp/ptp.aspx
Janssen Pharmaceuticals, Inc. (n.d.). SPRAVATO® Risk Evaluation and Mitigation Strategy (REMS) Program. SPRAVATO. Retrieved from https://www.spravato.com/spravato-available-treatment-centers/
Janssen Pharmaceuticals, Inc. (n.d.). How to Use SPRAVATO® & Dosing. SPRAVATO. Retrieved from https://www.spravato.com/taking-spravato/
Janssen Pharmaceuticals, Inc. (n.d.). SPRAVATO® Savings and Support. SPRAVATO. Retrieved from https://www.spravato.com/
Janssen Pharmaceuticals, Inc. (n.d.). Major Depressive Disorder with Suicidal Thoughts or Actions (MDSI). SPRAVATO. Retrieved from https://www.spravato.com/spravato-available-treatment-centers/
Janssen Pharmaceuticals, Inc. (n.d.). Find a SPRAVATO® Treatment Center. SPRAVATO. Retrieved from https://www.spravato.com/spravato-available-treatment-centers/
New Mexico Human Services Department. (2024). Final LOD 103: State Fiscal Year 2024 payment rate increases. New Mexico HSD. Retrieved from https://www.hsd.state.nm.us/wp-content/uploads/Final-LOD-103-State-Fiscal-Year-2024-Payment-Rate-Increases_wAttachment.pdf
Osmind. (2021, March 17). SPRAVATO® REMS automated patient monitoring form. Osmind. Retrieved from https://www.osmind.org/knowledge-article/spravato-notes-and-rems-submission
Osmind. (n.d.). The comprehensive guide to integrating SPRAVATO® in your practice. Osmind. Retrieved from https://www.osmind.org/knowledge-article/comprehensive-guide-integrating-spravato-practice
Osmind. (n.d.). SPRAVATO® patient and provider questions. Osmind. Retrieved from https://www.osmind.org/knowledge-article/spravato-patient-provider-questions
Osmind. (n.d.). Leading ketamine platform. Osmind. Retrieved from https://www.osmind.org/knowledge-article/leading-ketamine-platform
Osmind. (n.d.). Expecting better: Expert perspectives on MDMA-AT's FDA journey. Osmind. Retrieved from https://www.osmind.org/knowledge-article/mdma-at-fda-journey
SPRAVATO® coverage and policy information. Policy Acumen. Retrieved from https://spravato.policyacumen.health/
SPRAVATO® healthcare providers. SPRAVATO HCP. Retrieved from https://www.spravatohcp.com/
Spravato Side Effects: Common, Severe, Long Term. (n.d.). Drugs.com. Retrieved from https://www.drugs.com/sfx/spravato-side-effects.html
Spravato® (esketamine) - Prior Authorization/Medical Necessity - UnitedHealthcare Commercial Plans. (2024). UnitedHealthcare. Retrieved from https://www.uhcprovider.com
SPRAVATO® REMS Program Overview. (n.d.). Janssen Pharmaceuticals. Retrieved from https://www.spravatorems.com/
