The Use of Ketamine to Treat Mental Health Disorders and Pain: Managing the Risks

The recent death of actor Matthew Perry and the subsequent arrest of two physicians who provided him with ketamine hydrochloride (ketamine) have cast a spotlight on the use of ketamine therapy to treat mental health disorders. FDA approved since 1970, ketamine is a short-acting, injectable anesthetic for human and animal use. Referred to as a “dissociative anesthetic hallucinogen,” ketamine induces hallucinations and a feeling of detachment in patients. In 2019, the FDA approved Spravato® (esketamine) nasal spray, a ketamine derivative, for treatment-resistant depression only when administered by certified prescribers in clinical settings under a Risk Evaluation and Mitigation Strategy (REMS) drug safety program.

Ketamine is only FDA-approved for use as an anesthetic and short-term sedative, but data gathered over the past few years has shown its effectiveness in treating depression, post-traumatic stress disorder, obsessive-compulsive disorder, and anxiety. It has also shown promise in managing chronic pain that is not responsive to other medications or treatment modalities.

When used to treat mental health disorders and pain, ketamine is administered in dosages lower than those used for anesthesia. Ketamine-assisted psychotherapy (KAP) is a treatment modality involving intravenously, intramuscularly, or sublingually administered ketamine combined with active psychotherapeutic support. When skilled, well-trained providers administer the medication to appropriately screened patients in supervised settings, ketamine can be an effective tool in treating many complex and difficult medical and psychiatric conditions.

Despite soaring popularity, concerns remain about the risks associated with ketamine and esketamine given the potential for abuse, prevalence of false and misleading claims, ease of online availability, and possible side effects. When ketamine and esketamine are administered incorrectly or without sufficient screening or monitoring, death, excessive sedation, cardiovascular events, psychological issues, and misuse can result. Alterations in motor function, cognition, and perception can last for hours after administration of the drug has been completed. During this time, the patient may not be able to think clearly or make rational decisions. Their perception and mobility may be altered, which may make them react atypically to stimulus. Consequently, patients who receive ketamine therapy require extended monitoring before being discharged from the facility.
 

Risk Management Recommendations

Ketamine and its derivatives are increasingly being used in multiple settings to treat various disorders. Accordingly, implementation of solid policies and procedures and assessment of care team competencies are essential to minimizing risk exposure. Consider the following when evaluating the use of ketamine to treat mental health disorders and pain in your organization:

• Know the law. State laws vary widely regarding the acquisition, prescription, administration, and dispensation of ketamine and esketamine. Work with an attorney to understand your state laws regarding requirements for facility licensure and staffing and for practitioner certification, licensure, and/or training. Ensure that your licensure, policies, procedures, and patient-facing forms comply with state and federal law.
• Ensure competence. Establish credentialing and scope of practice guidelines for practitioners and staff who prescribe or administer ketamine and/or esketamine. Ensure that competency is assessed and documented upon hire and on a regular basis.
• Develop policies and procedures. Ensure that policies, procedures, and protocols regarding the prescription and administration of ketamine are evidence-based and reflect the current state of knowledge regarding the use of ketamine to treat mental health disorders and chronic pain. Develop and adhere to dosing guidelines specific to the condition being treated. Use extreme caution when prescribing compounded or oral ketamine products as these may pose unique patient safety risks, especially when they are used at home without appropriate medical monitoring. 
• Screen patients. Develop clear guidelines on patient screening and selection to ensure only patients who are appropriate for therapy are selected. Pregnant patients and those with cardiovascular disease, liver disease, hypertension, and psychiatric disease associated with psychosis may not be appropriate for ketamine therapy. Carefully consider patient age and the potential for misuse before initiating treatment. 
• Communicate and collaborate. Patients should understand when ketamine administration is part of a comprehensive treatment plan and should be willing to devote the necessary time. Communicate and collaborate with other practitioners on the patient’s care team to ensure that their input is considered. Obtain general or specialty medical clearance when indicated based on the patient’s medical or psychiatric history. 
• Obtain a thorough history. Complete a thorough history and physical examination to identify any contraindications or conditions that may exclude a patient from therapy or lead to an increased risk of side effects. Include a thorough psychiatric history and review available records to determine appropriateness for treatment and rule out current or past diagnoses of substance use disorder or psychotic disorders. Consider obtaining a urine drug screen to confirm the patient’s reported substance use. Obtain pre-procedure labs as appropriate. 
• Obtain informed consent. Obtain written informed consent from the patient for ketamine use at every visit. Provide the patient with a literature-based assessment of risks, benefits and alternatives to treatment and/or no treatment at all, explain potential treatment side effects, what will occur during the treatments, the number and frequency of treatments required, and the cost associated with therapy. Obtain written consent before commencing treatment and ensure that no other medications have affected the patient’s ability to provide informed consent. File a copy of the signed consent form in the medical record. Document the consent discussion along with the education provided and the patient’s confirmation that their questions and/or concerns were answered or resolved prior to starting the treatment encounter. 
• Provide medical monitoring. Develop guidelines for monitoring and documenting patient status during and after the treatment encounter. Measuring and monitoring heart rate, blood pressure, oxygen saturation, and level of consciousness is the minimum level of monitoring recommended during ketamine infusions or intranasal therapy. Require the patient to remain on-site for monitoring until the effects of ketamine/esketamine wear off, usually about two hours for most patients. Assess the patient prior to discharge to ensure clinical stability and readiness to leave the healthcare setting. Consider using a standardized safety tool, such as the Ketamine Side Effect Tool (KSET) for monitoring patients, when initiating ketamine to decrease the chance of creating dependency. 
• Prepare for emergencies. Anticipate and plan a response to potential medical emergencies. Ensure that the proper equipment is available and staff are trained to address unanticipated treatment outcomes, including airway management, emergency transportation, and other resuscitation efforts.
• Document. Document the decision-making process for selecting ketamine therapy, along with other medications and treatment modalities that have been tried without results. Ensure that documentation of each office visit contains an assessment of the patient’s potential for addiction and suicidal ideation.

Certain patient populations may benefit from ketamine therapy when administered by well-trained practitioners to properly screened patients. Proactive risk mitigation efforts can help alleviate fears and ensure that this treatment is provided effectively, efficiently, and within community guidelines.
 

Additional Resources 

 

• American Association of Nurse Anesthesiology. Ketamine Therapy Overview and Clinical Practice Guidelines.
• Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists.