Ketamine, historically used as an anesthetic, has emerged as a rapid-acting intervention for severe, persistent depression. Its mechanism of action differs significantly from traditional antidepressants, offering hope when other treatments have failed. This therapeutic approach is not a first-line treatment and is subject to significant regulation due to its potency and classification as a Schedule III controlled substance. Accessing ketamine requires navigating a precise medical pathway, starting with a determination of clinical necessity and eligibility.
Determining Clinical Eligibility
The primary criterion for ketamine treatment is a diagnosis of Treatment-Resistant Depression (TRD). This means the individual has not achieved sufficient symptom relief after trying at least two different classes of antidepressant medications at adequate doses and for a reasonable duration. Physicians must conduct a comprehensive psychiatric assessment to confirm TRD status and rule out other conditions. This ensures the patient has exhausted standard pharmaceutical approaches before escalating treatment.
A thorough medical screening is also performed to identify contraindications that would make ketamine use unsafe. Conditions that typically disqualify a candidate include uncontrolled hypertension, a history of aneurysmal vascular disease, or an active substance use disorder. A history of psychosis or mania also requires careful consideration, often excluding the patient. The prescribing physician must confirm the patient is not pregnant and does not have acute cardiovascular disease before proceeding.
Types of Approved Ketamine Delivery Methods
The method of administration defines the regulatory environment and treatment setting. Racemic ketamine, the original compound, is most often delivered via intravenous (IV) infusion in specialized clinics. This IV method is considered an off-label use for depression, meaning the FDA has not specifically approved it for this indication, though it is supported by clinical research. IV infusions typically last 40 minutes to an hour, during which the patient is closely monitored for side effects such as temporary blood pressure changes or dissociation.
The only FDA-approved formulation for depression is esketamine, a derivative of ketamine available as an intranasal spray (Spravato). Esketamine is approved for TRD and for depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior. Its prescription is highly regulated by the mandatory federal Risk Evaluation and Mitigation Strategy (REMS) program. This program mandates that the medication only be administered in a certified healthcare setting under the direct observation of a provider. The patient must also be monitored for at least two hours after administration.
Another delivery method involves sublingual lozenges or troches, which are compounded forms of ketamine for oral use. These are prescribed off-label and are sometimes utilized for maintenance therapy or in-home use, requiring stringent physician oversight. Compounded oral forms are generally less expensive than in-clinic methods but involve less direct monitoring, which carries different safety considerations.
Navigating the Prescription and Treatment Process
Obtaining a prescription begins with finding a qualified provider, such as specialized psychiatrists, certified ketamine clinics, or REMS-certified medical offices for esketamine. An initial, in-depth consultation is necessary to review the patient’s medical and psychiatric history, confirming the TRD diagnosis and evaluating potential safety risks. This comprehensive intake often lasts an hour and a half.
Once eligibility is established, treatment moves into the induction phase, an intensive period designed to achieve a rapid reduction in symptoms. For IV ketamine, this generally involves six to eight infusions administered over two to three weeks. Esketamine treatment typically starts with a twice-weekly dosage for the first four weeks. In both cases, the patient must remain under professional observation during and for a specified time after the session due to the risks of sedation and elevated blood pressure.
Following the initial phase, a patient who responds well transitions to a maintenance phase with less frequent sessions. This phase may involve weekly, bi-weekly, or monthly treatments, depending on individual needs and symptom stability. Some providers may switch patients to a compounded oral ketamine regimen for maintenance, though this is an off-label decision. Ongoing communication with a mental health provider is required to manage the treatment plan and monitor for sustained improvement.
Understanding Costs and Coverage
The financial commitment for ketamine therapy varies substantially based on the delivery method and insurance coverage status. The FDA-approved esketamine nasal spray is more likely to be covered by insurance, including Medicare and many private plans, because it is an on-label treatment. Even with coverage, patients often navigate a prior authorization process and pay co-pays for the medication and the required two-hour monitoring fee.
In contrast, IV ketamine infusions are almost always considered an out-of-pocket expense because this off-label use is not covered by most insurance plans. A single IV infusion session typically ranges from $400 to $800, meaning an initial induction series can cost between $2,400 and $6,400. Patients receiving esketamine without insurance may face costs of $900 to $1,300 per session, including the drug and monitoring fees. An insured patient’s out-of-pocket expense may be as low as a standard co-pay.
Patients may explore patient assistance programs offered by the manufacturer for esketamine to help offset the medication cost. However, these programs do not typically cover the clinic’s administration and monitoring fees. The cost for compounded sublingual ketamine is generally lower, ranging from $100 to $250 per session, but this method is also not covered by insurance. Prospective patients must prepare for a substantial financial commitment, especially for the intensive induction and maintenance treatments.