Over several decades, research has shown that ketamine has antidepressive properties. Ketamine is approved by the U.S. Food and Drug Administration (FDA) for the induction and maintenance of anesthesia, although it is also being used for the management of psychiatric disorders and chronic pain management. Ketamine has been incorporated into the treatment of psychiatric disorders, such as major depressive disorder (MDD), bipolar disorder, and post-traumatic stress disorder (PTSD), as well as post-operative and chronic pain management. Intravenous (IV) ketamine therapy is not a first-line therapy for psychiatric disorders or chronic pain management and may be considered by the patient’s interdisciplinary team after failure of standard treatment.1 Please note that esketamine nasal spray, a derivative of ketamine, has been separately approved by the FDA for treatment-resistant depression.
Ketamine infusion therapy involves the administration of a single infusion or a series of infusions for the management of psychiatric disorders (e.g., major depressive disorder, post-traumatic stress disorder, acute suicidality). Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has traditionally been used for the induction and maintenance of anesthesia. As ketamine infusion clinics in healthcare facilities become available, psychiatric-mental health advanced practice nurses (APRNs) and psychiatric-mental health RNs are collaborating with certified registered nurse anesthetists (CRNAs) to provide ketamine therapy services for individuals with chronic and medication resistant mental health disorders.1
Ketamine Treatment Considerations Checklist
This checklist provides considerations for prescribing ketamine infusion therapy and is not intended to be all inclusive.
State Scope of Practice
Review applicable state nursing, medical, drug and facility statutes and regulations to identify existing and anticipated practice barriers.
Verify whether the state board of nursing or other relevant board has issued a related opinion applicable to RNs and/or APRNs.1
Individuals diagnosed with bipolar disorder (with managed mood stabilization)
Individuals diagnosed with personality disorders (provided individual can manage infusions and engage in therapy)2
Considerations for Candidate Eligibility
Currently, there are limited empirically established recommendations for the use of ketamine treatment in psychiatric disorders. Therefore, the selection of appropriate candidates for ketamine treatment requires careful consideration regarding the risks and benefits of the treatment in context of the individual’s severity of depression, duration of current episode, previous treatment history, and urgency for treatment.
Intravenous (IV) ketamine therapy should not be considered for the initial treatment for psychiatric disorders or chronic pain management.
Ketamine therapy should only be considered after failure of standard treatment:
No sustained change following adequate antidepressant trials (some individuals will have tried several different anti-depressants), different medication combinations, and/or ECT/TMS.
No sustained change in response to adjunctive group CBT or individual therapy.
Evaluation of the contraindications to ketamine.1
Ketamine Therapy Exclusion
Active substance abuse (Alcohol, cannabis, non-prescribed medications, etc.)
Negative urine toxicology screening prior to the initiation of treatment to prevent risk of precipitated mania
History of psychosis
History of increased intracranial pressure
Acute or unstable cardiovascular disease
Previous negative response to ketamine2
Obtain Medical and Substance Use History
Comprehensive diagnostic assessment to rule out diagnosis of current and past substance use and psychotic disorders.
A baseline urine toxicology screen is recommended to ensure the accuracy of the reported substance use and medication record.
Detailed and thorough history of previous antidepressant treatment to confirm adequate trial.
Thorough review of past medical and psychiatric records and/or confirmation of the past history by family members are strongly encouraged. All current medications and allergies should be reviewed, including histories of opiate and benzodiazepine use.
Obtain baseline symptom severity to later assess clinical change with treatment.1
Process for Referrals
Individual should verify insurance coverage (e.g., private, Medicare, Medicaid)
Obtain credentialing for ketamine infusion or collaborate with credentialed provider
Document pertinent information on the individual’s healthcare record in an accurate, complete, legible, and timely manner
Include risks, benefits, and potential side effects, as well as alternative therapies and their risks, benefits, and potential side effects
Manage Treatment Expectations
Consult ketamine package insert and current literature for drug-specific considerations, contraindications, dosages, side effects, etc.
Pre-Treatment Medical Consultation
History and physical
Patient receives medical clearance
General medical clearance
Specialty medical clearance (e.g., cardiac, neurological) as necessary based on history
Pre-procedure labs (e.g., liver function tests, creatinine)
Establish process for infusion and medication orders
Evaluate contraindications to ketamine
Administer pre-medication, as appropriate, to mitigate adverse events
Consider recommending trial infusions to assess for responsiveness, efficacy, and tolerability of side effects prior to prolonged treatment. Standard course of treatment is usually a three-treatment trial (IV infusion every other day or twice per week x 3) to assess responsiveness to ketamine treatment
Administration Protocol of Ketamine by an Appropriate Provider
Dosage (Dosage is weight based and standard)
Infusion time (typically infused over 40 minutes)
Frequency (typically twice per week for 4-5 weeks with taper)
Monitoring individual receiving ketamine during infusion
Patient sent home with appropriate driver/caregiver1
Establish an emergency response system
Recovery to pre-administration vital sign baseline levels
Absence of dissociative effects
Psychiatric evaluation post-treatment to assess effects, suicidality, etc.
Patients should be monitored closely using a rating instrument to assess clinical change to better reevaluate the risk to benefit ratio of continued treatment. Assessments of cognitive function, urinary discomfort, and substance use should be considered if repeated administrations are provided (eBox 4 in the Supplement).
Considering the known potential for abuse of ketamine, clinicians should be vigilant about assessing the potential for patients to develop ketamine use disorder.
The number and frequency of treatments should be limited to the minimum necessary to achieve clinical response.3
Treatment regimen - # infusions administered over # days
Continuous Quality Improvement
Tracking adverse events
Drug Disposal and Diversion Prevention
Implement proper drug disposal and wasting measures consistent with federal, state, and local law to prevent drug diversion and misuse.
Many insurers may not cover
Establish fee schedule
Establish collection method for self-pay patients
Know how clinic is billing for your services
Educate billing staff
Identify applicable billing codes treatment1
The APNA Board of Directors would like to thank the members who contributed to the development of this resource: Paula Bolton, MS, APRN-BC; Julie A Carbray, PhD, FPMHNP-BC, PMHCNS-BC, APN; Rise Mitchell, BSN, RN, DNP, PMHNP; Mary Ann Nihart, MA, APRN, PMHCNS-BC, PMHNP-BC