Ketamine therapy uses low doses of ketamine, a decades-old anesthetic, to treat severe depression that hasn’t responded to standard antidepressants. Unlike traditional medications that can take weeks to show results, ketamine can reduce depressive symptoms within hours to days. It’s typically delivered through an IV drip in a clinical setting, though a nasal spray version called Spravato (esketamine) is the only form with FDA approval specifically for depression.
How Ketamine Works in the Brain
Most antidepressants target serotonin or norepinephrine. Ketamine works through an entirely different system: glutamate, the brain’s primary excitatory chemical messenger. By blocking a specific receptor called NMDA, ketamine triggers a chain of events that increases glutamate activity in the prefrontal cortex, the area of the brain involved in mood regulation, decision-making, and emotional processing.
That burst of glutamate activity is just the first step. It leads to the release of a protein called BDNF, which acts like fertilizer for brain cells. BDNF activates a signaling pathway that promotes the growth of new dendritic spines, the tiny structures that neurons use to communicate with each other. In animal studies, ketamine exposure led to rapid increases in several markers of synaptic plasticity in the prefrontal cortex. Depression is associated with the loss of these synaptic connections, so ketamine essentially helps rebuild the wiring that depression has degraded. This process, called synaptogenesis, is widely believed to be the core reason ketamine works so quickly compared to conventional antidepressants.
Who Qualifies for Treatment
Ketamine therapy is primarily used for treatment-resistant depression (TRD), defined as depression that hasn’t improved after trying at least two different antidepressants at adequate doses and durations. The FDA-approved nasal spray, Spravato, carries two specific indications: treatment-resistant depression in adults (either alone or alongside an oral antidepressant), and depressive symptoms in adults with major depressive disorder who have active suicidal ideation or behavior.
Not everyone with severe depression is a candidate. International consensus guidelines recommend excluding patients with uncontrolled hypertension, unstable cardiovascular conditions, aneurysmal disease, significant heart valve disease, recent heart attack, or advanced heart failure. A baseline blood pressure above 140/90 is generally considered a reason to hold off on treatment. Patients with a history of psychosis or active substance abuse may also be excluded, since ketamine can produce dissociative effects and carries some potential for misuse.
IV Ketamine vs. Nasal Spray
The two most common clinical delivery methods are intravenous (IV) ketamine and intranasal esketamine (Spravato). IV ketamine uses the generic drug at a standard dose of 0.5 mg/kg of body weight, infused over about 40 minutes. Some patients respond to doses as low as 0.1 mg/kg, while others need up to 0.75 mg/kg. Because this is an off-label use of a generic drug, insurance coverage is often limited.
Spravato, the nasal spray, delivers esketamine (a mirror-image molecule of ketamine) in fixed doses of 56 or 84 mg. As an FDA-approved product for specific indications, it has a clearer path to insurance coverage, though prior authorization is common. Both forms require administration under medical supervision. Other routes, including sublingual tablets and intramuscular injections, exist but are less standardized and typically compounded by specialty pharmacies.
What a Typical Treatment Course Looks Like
Treatment generally has two phases. The acute phase involves a series of sessions designed to achieve an initial response. A common protocol is six IV infusions given every other day over about two weeks, though some clinics schedule three sessions per week for the same period. During each session, you sit in a reclining chair while the infusion runs for roughly 40 minutes. Medical staff monitor your blood pressure, heart rate, and oxygen levels throughout.
After the infusion ends, you’ll stay for an observation period. Most people feel the dissociative effects begin to fade within 15 to 30 minutes after the drip stops, but you won’t be allowed to drive yourself home. Plan for the entire visit to take about two hours.
If the acute phase works, the maintenance phase begins. There’s no universal schedule for ongoing sessions. The antidepressant effect wears off at different rates for different people, so clinicians typically work with you to find the right interval through trial and error. For many patients, this ends up being roughly every three to four days initially, then gradually stretching to longer intervals over time. Some people continue maintenance sessions for months or even years.
Side Effects During and After Sessions
The most noticeable acute effect is dissociation: a feeling of disconnection from your body, surroundings, or sense of time. Some people describe it as dreamlike or floating. This is temporary and typically resolves within an hour of treatment ending. Other common short-term effects include drowsiness, increased blood pressure, nausea, and dizziness.
The blood pressure increase is one reason cardiovascular screening matters before starting treatment. Your vitals are monitored throughout the session specifically to catch any concerning spikes. Nausea can often be managed with anti-nausea medication given before the infusion.
Long-term risks are less well characterized but worth knowing about. The FDA has flagged several concerns with ketamine products, including the potential for abuse and misuse, psychiatric events, respiratory depression (slowed breathing), and lower urinary tract and bladder symptoms. Bladder problems have been well documented in chronic recreational ketamine users and involve inflammation and irritation of the bladder lining. Whether the lower, clinical doses used in depression treatment carry the same risk over extended maintenance periods is still an open question, but it’s something to discuss with your provider if you’re on a long-term protocol.
At-Home Ketamine and Safety Concerns
A growing number of telehealth companies offer compounded oral ketamine tablets or lozenges for at-home use. The FDA has issued specific warnings about this practice. Without on-site monitoring by a healthcare provider, patients are at risk for serious adverse events from sedation and dissociation. In one 2023 case reported to the FDA, a patient taking compounded oral ketamine at home for PTSD experienced respiratory depression, with blood levels roughly twice what’s typically seen during surgical anesthesia. Compounded ketamine products are not FDA-approved, and their dosing consistency can vary.
Cost and Insurance Coverage
A single IV ketamine infusion typically costs between $400 and $800. A full acute course of six sessions runs roughly $2,400 to $4,800 before any insurance considerations, plus the ongoing cost of maintenance sessions. Most insurance companies still classify IV ketamine for depression as experimental, so coverage is limited or nonexistent. Some plans offer partial coverage when traditional treatments have failed and a provider documents medical necessity.
Spravato tends to have better insurance coverage because of its FDA approval, but it still requires prior authorization and is only covered for the specific approved indications. Out-of-pocket costs for Spravato can also be significant without insurance, though the manufacturer offers copay assistance programs for eligible patients. At-home oral ketamine from telehealth providers is generally the least expensive option per session, but it falls outside FDA oversight entirely and comes with the safety trade-offs described above.