Ketamine Therapy for Treatment-Resistant Depression

Ketamine acts on the glutamate system and produces measurable antidepressant effects within hours to days of the first infusion, compared to the four-to-six-week onset typical of SSRIs. In the landmark studies by Zarate and colleagues at NIH, 71% of patients with treatment-resistant depression met response criteria at 24 hours after a single infusion, though the effect wanes without repeated dosing. This is why standard clinical practice uses a six-infusion induction over two to three weeks followed by individualized maintenance based on symptom trajectory.

Clinically administered intravenous ketamine at sub-anesthetic antidepressant doses has a very low addiction liability compared to recreational ketamine use. In fact, ketamine has been studied as a treatment for alcohol use disorder and cocaine use disorder with promising early results. At RECO Health, ketamine is delivered by anesthesia-trained clinicians in a controlled setting, not prescribed as a take-home medication. Patients in early recovery are screened carefully, and infusions are integrated with ongoing addiction therapy rather than replacing it.

Each infusion runs approximately 40 minutes in a private, dimmed treatment room with a reclining chair. A licensed nurse places an IV, attaches continuous pulse oximetry and blood pressure monitoring, and starts the ketamine infusion at 0.5 mg per kg of ideal body weight. Most patients experience mild dissociation — a sense of floating or altered time perception — that peaks around minute 20 and resolves within 20 to 30 minutes of infusion end. A monitored recovery period follows, and patients are cleared for discharge with a driver approximately 90 minutes after arrival.

IV racemic ketamine for depression remains an off-label use of an FDA-approved anesthetic, so most commercial insurance plans do not cover the infusions themselves as of 2026. Some plans reimburse a portion under out-of-network mental-health benefits, and Spravato — the intranasal esketamine that is FDA-approved for treatment-resistant depression — is covered by most plans when medical necessity criteria are met. Our admissions team runs a full benefits check within 24 hours of your call and lays out the covered, out-of-pocket, and financing options so there are no surprises.

IV ketamine is the racemic mixture of R- and S-ketamine given intravenously; Spravato is the S-enantiomer (esketamine) given as a nasal spray. IV ketamine is off-label but has a larger, longer-standing evidence base and typically produces a faster and more complete antidepressant response. Spravato is FDA-approved for treatment-resistant depression and depression with suicidality, is REMS-controlled, and is covered by most insurance — but requires twice-weekly visits during induction and two hours of in-office monitoring per dose. RECO Health offers both and helps patients choose based on response history, insurance coverage, and scheduling.

Response to a six-infusion induction typically lasts one to three months without additional treatment; some patients relapse within days, others stay well for over a year. Maintenance strategy is individualized: many patients receive a booster infusion every four to eight weeks based on symptom trajectory, others transition to an oral maintenance strategy with an SSRI/SNRI plus low-dose lithium or an atypical antipsychotic augmentation. Our psychiatric team tracks PHQ-9 and MADRS scores weekly and adjusts the maintenance schedule to the individual response curve rather than a fixed protocol.

Absolute contraindications include uncontrolled hypertension, active psychosis, primary psychotic disorders, history of increased intracranial pressure or intracranial mass, untreated hyperthyroidism, and pregnancy. Relative contraindications include severe cardiovascular disease, severe hepatic impairment, and active substance use of ketamine or other dissociatives. We screen every candidate with a full psychiatric evaluation, medical history review, and baseline vitals; approximately one in seven referred patients is redirected to an alternate treatment because ketamine is not appropriate.

Yes, and this is standard clinical practice. Ketamine is nearly always used as augmentation rather than monotherapy. Patients continue their existing SSRI, SNRI, atypical antipsychotic, lithium, or lamotrigine during induction and maintenance. Benzodiazepines are held on the morning of infusion because they blunt the antidepressant response. Ongoing therapy — CBT, DBT, EMDR, and addiction-focused counseling — is not just compatible but strongly encouraged, and the neuroplastic window opened by ketamine appears to enhance therapy uptake in the days after each infusion.