During the Vietnam War, it became a widely used anesthetic in theaters of operation where concerns about hemodynamic instability are paramount in wounded service members and has now been in clinical use for more than 50 years. In fact, studies show that 59% of patients respond positively after repeated ketamine infusions, with most achieving significant improvement after just three sessions. Once we know you are responding well, after your first few treatments, we will recommend a frequency of dosing that aims to sustain the results.
As a result, you will see effectiveness categorized as high, medium, or low rather than exact percentages. – While oral ketamine appears safe and moderately effective, its ability to deliver full remission remains uncertain and requires confirmation from larger studies. – The findings suggest that while esketamine may provide some benefit, its overall impact appears limited, especially in cases where rapid relief from suicidal ideation is needed.
At anesthetic doses, ketamine induces a state of dissociative anesthesia, a trance-like state providing pain relief, sedation, and amnesia.21 Its distinguishing features as an anesthestic are preserved breathing and airway reflexes, stimulated heart function with increased blood pressure, and moderate bronchodilation.21 As an anesthetic, it is used especially in trauma, emergency, and pediatric cases. At lower, sub-anesthetic doses, it is used as a treatment for pain and treatment-resistant depression. Overall, we conclude there is limited direct evidence supporting the preemptive use of benzodiazepines and α2 agonists and no evidence to support antidepressant, antihistamine, or anticholinergic premedicants prior to the initiation of subanesthetic ketamine for chronic pain treatment (grade C recommendation, low level of certainty). Clinical data reveals that ketamine’s antidepressant effects typically last from a few days to 2 weeks per session. Repeated administrations produce more robust therapeutic outcomes compared to single infusions.
- Thereafter, the enhanced brain plasticity supports the formation of new neural pathways, making behavioral changes more sustainable.
- Perry himself was using ketamine infusion therapy for depression and anxiety, with the most recent infusion provided a week and a half before his death, his autopsy report said.
- Despite the promising response and remission rates, the effect sizes reported across studies were small (typically between 0.15 and 0.23).
- Ketamine infusion therapy is delivered at a dosage that is less than you would get if you were receiving ketamine for anesthesia, but some of the side effects might seem similar.
- But even though ketamine works quickly, the effects wane after a few days or weeks, research has shown.
Ketamine has been known to treat serious depression
Considering the growing recognition of its abuse potential,214–217 a history of alcohol or other substance abuse is mentioned in several Web sites, drug monographs, and case reports as a relative contraindication to ketamine use. Unlike for acute pain in which there is a widely accepted mandate for urgent treatment, infusions are generally given on a 1-time basis, and the therapeutic alternatives (ie, high-dose opioids in an opioid-dependent individual) are often less appealing than ketamine; for chronic pain treatment, the use of a drug with abuse potential in a high-risk population may carry significant risks that outweigh the benefits. In summary, for spinal cord injury pain, there is weak evidence supporting ketamine infusions (0.42 mg/kg per hour to 0.4 mg/kg ranging from 17 minutes to 5 hours for 7 consecutive days) for short-term improvements in pain (grade C recommendation, low level of certainty). For CRPS, there is moderate evidence supporting ketamine infusions (22 mg/h for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days) to provide improvements in pain for up to 12 weeks (grade B recommendation, low to moderate level of certainty). For mixed neuropathic pain, PLP, PHN, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain, there was weak or no evidence supporting ketamine infusions for immediate improvements in pain (grade D, low level of certainty). Excluding CRPS, there was no evidence supporting ketamine infusions for intermediate or long-term improvements in pain.
Preclinical Evidence and Challenges in Translation: Can Ketamine Reverse or Halt Central Sensitization?
This comprehensive guide will help you understand how ketamine therapy works, its long-term effects, maintenance requirements, and safety considerations. You’ll learn everything you need to know about this innovative treatment approach and its potential role in your mental health journey. By looking at all the best available evidence, systematic reviews and meta-analyses help us avoid being misled by one-off results, ketamine infusion therapy effectiveness small sample sizes, or studies with flawed methods.
Ketamine infusion therapy stands as a powerful option for those seeking lasting relief from depression and anxiety. Research clearly shows that most patients experience significant improvements after just three sessions, while continued maintenance treatments help sustain these benefits long-term. Research indicates that some patients maintain improvement for several months between sessions, while others benefit from monthly treatments.
Medical
Proper monitoring and management of side effects play a vital role in successful ketamine therapy outcomes. First thing to remember, while ketamine infusion therapy shows promising results, understanding potential side effects and safety measures ensures optimal treatment success. The systematic reviews and meta-analyses compiled on this page represent research published in the last five years. While I have done my best to find the most relevant and high-quality studies, there may be additional research that I was unable to locate.
Ketamine is legally used in medicine but is also tightly controlled, as it is used as a recreational drug for its hallucinogenic and dissociative effects.22 When used recreationally, it is found both in crystalline powder and liquid form, and is often referred to by users as “Ket”, “Special K” or simply “K”. The long-term effects of repeated use are largely unknown and are an area of active investigation.232425 Liver and urinary toxicity have been reported among regular users of high doses of ketamine for recreational purposes.26 Ketamine can cause dissociation and nausea, and other adverse effects, and is contraindicated in severe heart or liver disease, and uncontrolled psychosis. Ketamine’s clinical and antidepressant effects can be influenced by co-administration of other drugs, though these interactions are variable and not yet fully understood. The recommendations in response to the questions we have addressed are often based on small randomized trials, observational and retrospective studies, clinical experience, and evidence extrapolated from the use of ketamine in other contexts and thus may change as better evidence emerges. This may be more relevant for the sections concerned with indications and, to a lesser extent, contraindications, which continue to evolve with more information. For example, adverse effects such as ketamine-induced psychosis may result from either 1-time use or cumulative effects (eg, psychosis, urinary tract dysfunction, liver disease),189,267,268 and as the serial use of ketamine for chronic conditions such as depression and pain continues to rise, and the prevalence of abuse increases commensurately, the indications, contraindications, and surveillance recommendations may change in concert.
- Recent clinical trials reveal promising results for ketamine infusion therapy, with 55% of patients experiencing sustained improvement in depressive symptoms without major side effects.
- In November 2016, the charge for developing consensus guidelines was approved by the boards of directors of the American Society of Regional Anesthesia and Pain Medicine and, shortly thereafter, the American Academy of Pain Medicine.
- Research shows significant improvements in depressive symptoms persist through a 5-week follow-up period, with 77% of patients showing sustained positive responses.
- Research indicates that some patients maintain improvement for several months between sessions, while others benefit from monthly treatments.
- The recommendations in response to the questions we have addressed are often based on small randomized trials, observational and retrospective studies, clinical experience, and evidence extrapolated from the use of ketamine in other contexts and thus may change as better evidence emerges.
- But in the only randomized trial focused on depression, combining psychotherapy with ketamine showed no significant benefit over ketamine alone (Journal of Affective Disorders, 2022).
The ketamine economy: New mental health clinics are a ‘Wild West’ with few rules
Regular assessment of cognitive function, urinary comfort, and substance use patterns helps maintain treatment safety with repeated administrations. Clinics should maintain a comprehensive emergency-response protocol and have exceptionally good “bedside manner,” being able to offer psychological support and encouragement well above-and-beyond typical nursing duties. Practitioners recommend avoiding ketamine therapy for pregnant women, individuals with uncontrolled hypertension, or those with severe cardiovascular disease. These numbers place IV ketamine among the most effective depression treatments ever studied—especially for people who haven’t responded to SSRIs, psychotherapy, or other standard options.
Systematic Reviews of IV Ketamine’s Effectiveness (in this section)
– The randomized controlled trials were marked by a high risk of bias, largely due to flawed analysis methods and inadequate monitoring of adverse events. The most consistent finding across reviews was that continuing esketamine beyond the 4-week induction phase may help prevent relapse. However, symptom relief often diminished after discontinuation, and the evidence for long-term effectiveness remains mixed. Multiple reviews called for larger, independent trials to clarify esketamine’s long-term value. So while oral ketamine might help some people, the current evidence shows it’s slower, less powerful, and far more uncertain than either IV or nasal administration.
In the absence of large, randomized studies, the establishment of ketamine treatment-based registries can help guide treatment decisions. These systematic reviews offer a more conservative—and arguably more realistic—portrait of esketamine than the data submitted to the FDA, which reported higher remission and response rates after long-term treatment. The discrepancy likely reflects differences between manufacturer-sponsored clinical trials and broader, independent evidence synthesis. Across five major systematic reviews and meta-analyses published between 2020 and 2024, between 27% and 43% of patients who received ketamine therapy for depression reported going into remission—meaning their symptoms became minimal or disappeared altogether (Brain Sciences, 2023; Molecular Psychiatry, 2022; Current Neuropharmacology, 2014; Frontiers in Psychiatry, 2024; Therapeutic Advances in Psychopharmacology, 2023). According to twelve systematic reviews and meta-analyses published between 2020 and 2024, between 30% and 76% of patients who undergo ketamine therapy for depression report at least a 50% reduction in symptoms—a benchmark known as clinical response (Therapeutic Advances in Psychopharmacology, 2023; Brain Sciences, 2023; Molecular Psychiatry, 2022; Current Neuropharmacology, 2014). Some reviews found that suicidal thoughts diminished within 40 minutes, though this wasn’t consistent across all studies (Current Neuropharmacology, 2014; Therapeutic Advances in Psychopharmacology, 2023).
Wyatt Technology’s DynaPro Plate Reader 4 integrates advanced light scattering techniques, optimizing workflows in biotherapeutic and nanoparticle research. If one critic raves about a film but every other reviewer says it’s awful, you probably shouldn’t trust just that one glowing review. – Esketamine produced a modest antidepressant effect, with effect sizes ranging from 0.15 to 0.23 on a scale where 0 indicates no effect and 1 indicates a very strong effect. This report ranks all three options—IV, injection, and Spravato—on effectiveness, cost, fastest relief, and more, giving you a clear framework to decide.
The provider will make sure that you are comfortable before you get started, and they will likely put a pulse oximeter on your finger and a blood pressure cuff on your arm so that they can monitor your vitals during the infusion. Let’s also discuss some tips that might be helpful to you if you receive ketamine infusion therapy. In 2019, Spravato (esketamine) was approved by the FDA for treatment-resistant depression (depression that hasn’t responded to at least two medicines). However, this is more common than you would think—more than 50% of people don’t respond to the first antidepressant they try.