VA CFU Criteria Formulary Advisor Reference
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ESKETAMINE SOLN,SPRAY,NASAL

Generic Name
ESKETAMINE SOLN
Brand Names
SPRAVATO
Drug Class
ANTIDEPRESSANTS,OTHER
Formulary Status
N
Copay Tier
3
Last Updated
2019-03-21

Clinical Criteria Summary

Document 66

Exclusion Criteria

  • Allergy or previous serious adverse effects to ketamine or esketamine
  • Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation
  • History of intracerebral hemorrhage
  • Uncontrolled seizures
  • Dementia
  • Current or recent (within 30 days) delirium
  • Current uncontrolled hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg)
  • Severe cardiac decompensation (Class IV heart failure or unstable angina)
  • Severe hepatic impairment (Child-Pugh class C)
  • Current or previous interstitial or ulcerative cystitis
  • Comorbid psychiatric condition is present (schizophrenia, schizoaffective disorder, bipolar disorder)
  • History of non-response to ketamine or esketamine
  • Current or previous abuse of ketamine or esketamine
  • Clinical evidence for current substance abuse except tobacco
  • Current barbiturate, cannabis, or opioid use
  • Current moderate or severe substance use disorder (SUD)
  • Pregnancy (known pregnancy or positive pregnancy test)
  • Breastfeeding/providing breastmilk to an infant

Primary Inclusion Criteria

  • Remission not achieved from 2 antidepressant trials including a trial of an augmentation strategy in the current episode of depression and 4 total adequate antidepressant trials in the patient’s lifetime
  • Patient is hospitalized with TRD with acute suicidal ideation/behavior
  • One augmentation trial could be an adequate course of evidence-based psychotherapy (EBP)

Additional Inclusion Criteria

  • All REMS requirements have been met
  • Adults <65 years of age with current diagnosis of unipolar major depressive disorder by DSM-5
  • Patient in current episode of depression is experiencing moderate to severe depressive symptomatology (i.e., PHQ-9 >15 within the last 30 days)
  • Antidepressant treatment trials are considered unsuccessful if the patient has not responded to at least 6 weeks of an antidepressant at half maximum dose or greater
  • A VA psychiatrist or a VA licensed health-care provider (i.e., CPP, NP, PA) has evaluated the patient and determined and documented in the patient’s medical records that the patient qualifies for esketamine treatment
  • The prescriber is a VA psychiatrist or a VA licensed health-care provider (i.e., CPP, NP, PA)
  • The patient agrees to stay and be monitored after esketamine administration and agrees not to drive or operate heavy machinery and not to make critical decisions for the remainder of the day in which esketamine is administered
  • The patient or their legal representative can provide signed informed consent
  • The patient has an adult who can accompany him/her and assist with transportation, or another method of safe transport has been arranged and documented

Specific Population Requirements

  • For women of childbearing potential: Pregnancy should be excluded prior to receiving esketamine and the patient provided contraceptive counseling on potential risks vs. benefits of taking esketamine if patient were to become pregnant

Document 788

Indications & Patient Selection

  • Treatment of treatment-resistant depression (TRD) or depressive symptoms in major depressive disorder (MDD) with acute suicidal ideation or behavior
  • Adults <65 years of age with current diagnosis of unipolar major depressive disorder by DSM-5
  • Patient in current episode of depression experiencing moderate to severe depressive symptomatology (PHQ-9 >15 within the last 30 days)

Inclusion Criteria

  • Remission not achieved from 2 antidepressant trials including a trial of an augmentation strategy in the current episode of depression AND 4 total adequate antidepressant trials in the patient’s lifetime
  • OR hospitalized with TRD with acute suicidal ideation/behavior
  • All REMS requirements have been met
  • Antidepressant treatment trials considered unsuccessful if patient has not responded to at least 6 weeks of an antidepressant at half maximum dose or greater
  • Evaluated and documented by a VA psychiatrist or VA licensed Mental Health-care provider (CPP, NP, PA) as qualifying for esketamine treatment
  • Prescriber is a VA psychiatrist or VA licensed Mental Health-care provider (CPP, NP, PA)
  • Patient agrees to stay/be monitored after administration and agrees not to drive/operate heavy machinery/equipment or make major financial/legal decisions for the remainder of the day
  • Patient or legal representative provides signed informed consent
  • Patient has an adult who can accompany/assist with transportation, or another method of safe transport arranged/documented
  • For women of childbearing potential: Pregnancy excluded prior to receiving; provided contraceptive counseling on risks vs benefits if pregnant

Exclusion Criteria

  • Allergy or previous serious adverse effects to ketamine or esketamine
  • Aneurysmal vascular disease (thoracic/abdominal aorta, intracranial, peripheral arterial vessels) or arteriovenous malformation
  • History of intracerebral hemorrhage
  • Uncontrolled seizures
  • Dementia
  • Current or recent (within 30 days) delirium
  • Current uncontrolled hypertension (SBP >140 mm Hg or DBP >90 mm Hg)
  • Severe cardiac decompensation (Class IV heart failure or unstable angina)
  • Severe hepatic impairment (Child-Pugh class C)
  • Current or previous interstitial or ulcerative cystitis
  • Comorbid psychiatric condition (schizophrenia, schizoaffective disorder, bipolar disorder)
  • History of non-response to ketamine or esketamine
  • Current or previous abuse of ketamine or esketamine
  • Clinical evidence for current substance abuse (except tobacco)
  • Current moderate or severe substance use disorder (SUD)
  • Pregnancy (known pregnancy or positive pregnancy test)
  • Patient is breastfeeding

Screening & Pre-treatment Requirements

  • Screening completed no more than 60 days prior to acceptance/administration of first dose
  • Signed informed consent
  • Psychiatric examination including assessment of inclusion/exclusion criteria
  • PHQ-9 depression rating scale required at screening and prior to each treatment
  • Evaluation of cognitive status (e.g., M-ACE)
  • Assessment of suicide risk: C-SSRS at intake/initial evaluation (and within 24 hours of discharge/clinically indicated); CSRE completed if first ever, otherwise updated as clinically indicated
  • Physical examination including vitals (BP, heart rate)
  • Relevant laboratory measures, urine toxicology, and pregnancy screens
  • Medical clearance from PCP or consultation from cardiologist/specialist based on risk factors (provider responsibility)
  • REMS Patient Enrollment Form completed and submitted

Dosing & Administration Parameters

  • Self-administered intranasally under direct observation of a Mental Health care provider in a certified medical facility
  • Ordering VA psychiatrist or VA licensed Mental Health-care provider physically present during dosing procedure
  • Induction Phase (Weeks 1-4): 56 mg or 84 mg twice per week
  • Maintenance Phase (Weeks 5-8): 56 mg or 84 mg once weekly
  • Maintenance Phase (Week 9 and after): 56 mg or 84 mg every 2 weeks or once weekly (individualized to least frequent dosing to maintain remission/response)
  • For MDD with acute suicidal ideation/behavior: 84 mg twice weekly x 4 weeks (may reduce to 56 mg twice weekly based on tolerability; use beyond 4 weeks not evaluated)
  • Stop dosing if pallor/cyanosis/poor perfusion, respiratory symptoms (shortness of breath/wheezing), chest/jaw/arm pain, or patient desire to stop

Monitoring & Recovery Requirements

  • Monitor for at least two hours after receiving dose
  • Esketamine cannot be dispensed directly to patient for home use
  • Monitoring location must be private, large enough for reclining head at 45 degrees, have crash cart/rapid access code team, monitor cardiovascular (ECG, BP) and respiratory function (O2 sat or end-tidal CO2), capable of administering oxygen/medications/restraints
  • Vital signs checks: T+20 min, T+40 min, T+90 min, T+120 min
  • At T+120 min: Check vital signs, C-SSRS Screener, readiness for discharge assessment (Modified Aldrete or bCAM)
  • REMS Patient Monitoring Form completed after every treatment session and submitted to Janssen
  • Longitudinal monitoring: PHQ-9 prior to each dose; PHQ-9 and cognitive evaluation at end of induction, every 6 months, and end of treatment course

Discontinuation & Treatment Failure Criteria

  • Do not move to maintenance therapy if no response after four weeks
  • Adequate response defined as ≥50% decline in PHQ-9 score from baseline
  • Stop drug and counsel on risks/benefits if woman becomes pregnant
  • Consider discontinuing if positive urine drug screen for specified drugs of abuse (cannabinoids, barbiturates, methadone, opioids, cocaine, phencyclidine, amphetamine/methamphetamine)
  • Discontinue if signs/symptoms of new or recurrent SUD emerge; refer to SUD specialty care

Source Documents

Document 66 Document 788