The Complete Guide To Ketamine Therapy
By Michael Alvear, Health Author & Independent Researcher
My research is published on these scholarly platforms:
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Here, you’ll find everything laid out in clear steps: what ketamine therapy is, what happens during a session, and how to figure out the costs. Whether you’re just curious or ready to take your first step, this is where your journey begins.
Can’t Decide Between IV, Injections, Or Spravato?
Use My Decision Table
This report ranks all three options—IV, injection, and Spravato—on effectiveness, cost, fastest relief, and more, giving you a clear framework to decide.
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Find The Nearest Ketamine Clinic To You
Locate trusted ketamine clinics in your area and take the first step toward treatment.
CITATIONS
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Clinician-facing chapters, consensus statements, labels, and patient monographs that ground this page’s clinical claims.
Ketamine – clinical overview (StatPearls, NCBI Bookshelf)
Clinician-facing overview of ketamine as an anesthetic and analgesic, outlining FDA-approved uses and common off-label indications including severe pain, treatment-resistant depression, suicidality, and refractory status epilepticus. Reviews mechanism of action, pharmacokinetics, IV/IM dosing ranges (including low-dose “sub-dissociative” use), adverse effects, contraindications, and monitoring requirements for safe practice.
International expert opinion review synthesizing evidence for ketamine and esketamine in adults with treatment-resistant depression. Evaluates efficacy, safety, and tolerability, and provides practical guidance on where these agents belong in treatment algorithms and what infrastructure, staffing, and monitoring are needed to implement them safely in real-world practice.
Ketamine treatment for depression – comprehensive review (Discover Mental Health, via PubMed)
Narrative review summarizing clinical data on IV racemic ketamine and intranasal esketamine for major depressive disorder and treatment-resistant depression, highlighting their rapid-onset but time-limited antidepressant effects. Also reviews use in other psychiatric conditions (suicidality, OCD, PTSD, substance use, social anxiety), discusses acute side effects and longer-term safety concerns (including abuse/dependence risk), and examines strategies such as repeat dosing or combination therapy to sustain benefit.
Spravato (esketamine) nasal spray – full prescribing information (FDA label, 2025 update)
Official 2025 U.S. prescribing information for Spravato, including boxed warnings for sedation, dissociation, respiratory depression, abuse/misuse, and suicidal thoughts and behaviors. Details approved indications (adult TRD and MDD with acute suicidal ideation or behavior), dosing schedules and evaluation at 4-week induction, REMS program requirements, contraindications, common adverse reactions, and key precautions such as blood-pressure monitoring and no driving until the next day after restful sleep.
Esketamine nasal spray – patient drug monograph (MedlinePlus, NIH)
Patient-oriented monograph explaining what esketamine nasal spray is, why it is prescribed (TRD and MDD with suicidal thoughts/behaviors), and how it is administered only in certified medical settings under the Spravato REMS program. Emphasizes major safety warnings (sedation, dissociation, suicidality, blood-pressure spikes), driving restrictions, common side effects, and what patients and families should watch for and report.
Spravato (esketamine) nasal spray – medical drug clinical criteria (Anthem policy PDF)
Anthem’s clinical policy summarizing the trial evidence for Spravato in treatment-resistant depression and MDD with acute suicidal ideation or behavior, and translating it into coverage criteria. It outlines labeled dosing schedules, required concomitant antidepressant use, monitoring and REMS requirements, and prior-authorization style rules about who qualifies and for how long treatment should be continued.
VA Pharmacy Benefits Management guidance for offering IV ketamine within the VA system for patients with treatment-resistant major depression or severe suicidal ideation. It reviews the evidence base, then specifies patient selection criteria, dosing (typically 0.5 mg/kg), required setting, staffing, monitoring, and documentation, emphasizing careful risk–benefit assessment and ongoing data collection on safety and effectiveness.
A patient-facing Mayo Clinic overview explaining how ketamine and esketamine differ from standard antidepressants, why they’re considered for treatment-resistant depression, and how they’re administered. It covers expected benefits and limits, common side effects and safety concerns (including misuse risk), and the kind of monitoring and collaborative care patients should expect if they pursue these options.
Systematic review and meta-analysis pooling randomized trials and other studies of oral ketamine for unipolar depression. It finds a statistically significant antidepressant effect with oral dosing but only marginal separation from placebo on response and remission rates, and no clear excess of adverse events, concluding that larger and longer studies are needed to define optimal dosing and long-term safety.
A qualitative clinical review synthesizing available data on practical parameters for ketamine treatment in depression: dose ranges, infusion rates, routes (IV, IM, SC, oral, intranasal, sublingual), and how often and how long to treat. It emphasizes that 0.5 mg/kg IV over ~40 minutes is the most studied regimen but that effective practice likely involves individualized balancing of dose, route, frequency, and duration, especially when treatment is extended over weeks to years.
Ketamine – comprehensive clinical monograph (StatPearls, NCBI Bookshelf)
Detailed reference chapter covering ketamine’s approved indications (anesthesia and analgesia), emerging psychiatric uses, mechanism of action, pharmacokinetics, dosing ranges, contraindications, and monitoring. Also summarizes acute and chronic adverse effects, toxicity, and best-practice guidance for safe clinical use across settings.
Ketamine – comprehensive clinical monograph (StatPearls, NCBI Bookshelf)
Same StatPearls/NCBI Bookshelf chapter as Source 11, providing an overview of ketamine’s pharmacology, clinical indications (including treatment-resistant depression and suicidality), dosing, side-effect profile, and toxicity/monitoring recommendations.
SPRAVATO® (esketamine) nasal spray – 2025 U.S. Prescribing Information (FDA label 211243s019)
Full FDA prescribing information for intranasal esketamine, including approved indications (treatment-resistant depression and MDD with acute suicidal ideation/behavior), dosing schedules, administration instructions, and REMS monitoring requirements. This 2025 supplement also updates safety information, adding bradycardia to the list of postmarketing adverse reactions and reiterating boxed warnings for sedation, dissociation, respiratory depression, abuse/misuse, and suicidality.
Secondary analysis of 108 treatment-resistant inpatients with MDD or bipolar depression receiving a single subanesthetic IV ketamine infusion, examining whether acute dissociation predicts antidepressant response. Increases in CADSS dissociation scores at 40 minutes were modestly correlated with greater later improvement in depression scores, while psychotomimetic symptoms, manic symptoms, and blood-pressure changes were not, suggesting—but not proving—that dissociation may be linked to clinical benefit.
Narrative review of a decade of ketamine-assisted psychedelic therapy work, focusing largely on randomized and follow-up studies in alcohol use disorder and other conditions. Reports that adding KPT to conventional alcoholism treatment substantially increased one-year abstinence rates (about 66% vs 24% with standard therapy alone), and discusses proposed mechanisms whereby ketamine-induced psychedelic experiences may facilitate lasting psychological and behavioral change.
Retrospective case-series of 29 patients with chronic non-malignant pain treated with sublingual ketamine troches/lozenges (25–600 mg/day in divided doses) for 2–89 months. The authors report clinically meaningful analgesia with reduced use of opioids, gabapentinoids, or benzodiazepines in 59% of patients (39% completely stopped at least one analgesic), side-effects in 24% with only 7% discontinuing due to drowsiness, and no observed cystitis, hepatotoxicity, or renal impairment—supporting an acceptable long-term safety profile in this context.
FDA safety communication emphasizing that ketamine is not approved for any psychiatric indication and that compounded ketamine products (including oral and sublingual forms obtained via telehealth/compounders) are not FDA-approved and lack established safe or effective dosing. It details risks such as sedation, dissociation, abuse/misuse, blood-pressure spikes, respiratory depression, and urinary/bladder symptoms, and highlights added dangers of unsupervised at-home use where vital-sign monitoring is absent, including an example of severe respiratory depression after oral compounded ketamine.
Ten common questions (and their answers) about off-label drug use (Mayo Clinic Proceedings)
Narrative review that explains what “off-label drug use” means, how common it is across specialties, and why it is legal even though the FDA has not approved those specific indications, doses, or dosage forms. The article walks through 10 practical questions on prevalence, evidence standards, patient consent, pharmaceutical marketing restrictions, and physician liability, framing when off-label prescribing is appropriate and how clinicians can minimize legal and ethical risk while prioritizing patient benefit.
Randomized, controlled trial sub-analysis of 22 patients with treatment-resistant depression receiving a single ketamine infusion versus midazolam, examining plasma brain-derived neurotrophic factor (BDNF) as a biomarker. Ketamine responders showed significant increases in plasma BDNF 240 minutes post-infusion compared with non-responders, and higher BDNF levels correlated with lower MADRS depression scores, suggesting peripheral BDNF may track ketamine’s rapid antidepressant effects.
Brief neuroscience commentary synthesizing animal and human data on how ketamine enhances synaptic plasticity and, critically, how the timing of those changes maps onto behavioral antidepressant effects. The authors propose a transient “window” of heightened neuroplasticity in the hours to days after ketamine during which experience and psychotherapy may be especially potent, and they outline how future studies should align behavioral interventions with this plasticity window.