PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study

Exclusion Criteria

• •Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
• •Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
• •Active or recent (within 12 months) substance use disorder (other than nicotine)
• •Pregnant or lactating women
• •Intracerebral hemorrhage or aneurysmal vascular disease
• •Hypersensitivity to ketamine, esketamine or any of the excipients
• •Known family history of ketamine use disorder
• •Prior known ketamine use disorder as well as subjects for whom study participations will result in more than 8 lifetime exposures to ketamine (e.g., prior exposure to ketamine, prior recreational use with ketamine)
• •Uncontrolled hypertension, as demonstrated by a blood pressure of greater than 145 / 90 at screening visit. (Pre-treatment blood pressure will be permitted to be 150 / 95 to allow for "whitecoat" hypertension on treatment visits 1-8.)
• •Known cardiovascular and cerebrovascular conditions that are associated with an increased risk related to ketamine or esketamine administration (including space-occupying CNS lesions). This includes those prospective participants who undergo EKG and are shown to have an abnormality that would put them at increased risk related to treatment.
• •Known condition for which an acute rise in blood pressure would pose a serious risk.
• •Arteriovenous malformation
• •Positive urine toxicology at screening visit, except for substances that are prescribed (i.e., benzodiazepines, stimulants). Given the extended length of time between exposure and negative toxicology screen, a positive screen for THC will not be exclusionary unless the pattern of use and clinical evaluation are indicative of cannabis use disorder. Cannabis used within 24 hours of dosing is exclusionary.
• •Positive alcohol breathalyzer at screening or clinical signs of intoxication
• •The patient is unable to arrange for someone to drive them home after each treatment session; patients who are unwilling to refrain from driving and operating machinery on treatment days until the next day following sleep will be excluded.