Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists

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 Treatment for Postpartum Depression: What Every Mom Should Know

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.

Esketamine appears to help a substantial number of patients during the induction phase, but the depth and durability of that benefit remain under investigation. Continued treatment may extend its impact, but stronger, longer-term trials are needed to understand how reliable and lasting that relief really is. Despite the promising response and remission rates, the effect sizes reported across studies were small (typically between 0.15 and 0.23). This suggests that while statistically significant, the magnitude of improvement may be less dramatic than the percentage figures alone might imply. I pulled together 33 systematic reviews from the last five years into one report—so you don’t have to rely on hype, guesses, or anecdotes. If you’re looking to start ketamine infusion therapy, this section will discuss how you can find a provider who offers this kind of treatment and what you can expect at your first appointment.

Relationships between levels and effects

Studies show that about 30% of people with depression do not respond sufficiently well to conventional antidepressants, which mostly target monoamine neurotransmitters, for example serotonin, dopamine and noradrenaline. One such novel treatment is the dissociative anaesthetic ketamine when given intravenously in low sub-anaesthetic doses. Ketamine works differently to other antidepressants and is believed to mediate its effects in the brain through the chemical messenger glutamate. This panel agrees with the APA recommendation that only a licensed physician who can administer a Drug Enforcement Administration Schedule III medication with Advanced Cardiac Life Support certification be in charge of administering ketamine, but because of the higher dosages used for chronic pain, we believe that person should also meet ASA requirements for the delivery of moderate sedation. For the person who actually administers subanesthetic IV bolus sedation, recommended credentials include a registered nursing degree with Advanced Cardiac Life Support certification, along with training in the administration of moderate sedation and specifically the pharmacology of ketamine.

• In summary, there is insufficient evidence supporting preinfusion testing prior to the administration of IV ketamine for chronic neuropathic pain conditions in healthy individuals.
• 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).
• Ketamine therapy can begin reducing depression symptoms or suicidal thoughts in as little as 40 minutes, with peak antidepressant effects typically emerging within 24 hours of a single infusion.

Guidelines

However, in the only RCT evaluating IV ketamine for cancer-related pain, a low-dose, 24-hour infusion of 1 mg/kg found no benefit in individuals who were receiving concomitant opioid therapy.164 In RCTs evaluating higher dosages administered as either serial outpatient infusions123 or an inpatient infusion161 for CRPS, significant improvement compared with placebo persisted for over 2 months. The American Psychiatric Association (APA) recently published consensus guidelines regarding the use of IV ketamine for treatment-resistant depression.5 These guidelines as well as other reports203,205,212 suggest few psychiatric contraindications. Large case series and systematic reviews indicate that there is an approximately 3.5% to 7.4% incidence of psychomimetic or dysphoric effects with IV ketamine.134,136,203,205 The majority of these effects involve transient hallucinations or dissociative, out-of-body sensations, none of which lead to self-injurious behavior, extreme agitation, or extended psychosis.

Clinical Implications

Improvements are often both cumulative and sustained, offering hope for those seeking long-term relief from depression. In one study, 85% of patients experienced a remission in their depressive symptoms (defined as at least a 50% reduction in symptoms). Patients relapsed (some symptoms returned) on an average of 19 days after, but some did not relapse for more than three months.

• The median response rate across these reviews was 55%, meaning that over half of patients experienced a major drop in depressive symptoms, often after just one or two infusions (Frontiers in Psychiatry, 2024).
• Guenter Corssen, MD, an anesthesiologist at the University of Alabama at Birmingham and author on that pivotal first manuscript,10 subsequently increased the dose in a stepwise fashion from no effect to “conscious but spaced out” and finally to a dose sufficient to produce general anesthesia.
• Graphical depiction of the relationship between ketamine dose and duration of analgesic benefit in randomized placebo-controlled trials that evaluated IV ketamine for chronic pain with a minimum of 48 hours’ follow-up.117,123,155,160–162,164 A trend line is been plotted to indicate the nature of this relationship.
• As an independent individual without institutional access to research databases or the financial resources to purchase paywalled studies, I have relied on publicly available sources.
• In several studies, patients who received therapy after ketamine experienced longer-lasting antidepressant effects and lower relapse rates compared to those who didn’t (Journal of Pain Research, 2022; British Journal of Psychiatry, 2023).

Overall, we conclude that there is moderate evidence to support higher dosages of ketamine over longer time periods, and more frequent administration, for chronic pain. Similar to the strategy used for opioids and other analgesic drugs with significant adverse effect profiles, it is reasonable to start dosing with a single, outpatient infusion at a minimum dose of 80 mg lasting more than 2 hours and reassess before initiating further treatments, similar to what is widely recommended for epidural steroid injections (grade C recommendation, low level of certainty) (Fig. 1). Recent clinical trials reveal promising results for ketamine infusion therapy, with 55% of patients experiencing sustained improvement in depressive symptoms without major side effects. The impact of ketamine therapy on long-term mental health outcomes has become increasingly significant, specifically with its ability to reduce depression symptoms within just 3-6 days.

Individuals respond with great variability to ketamine, so there is wide variation in hospital-based practices. Specific concerns regarding the monitoring of ketamine administration include airway protection, cardiovascular stimulation, the potential interaction of ketamine with concomitantly administered medications that may enhance certain effects (eg, midazolam), and the treatment of adverse effects. Medical screening before treatment identifies potential risk factors, primarily focusing on cardiovascular health and existing medical conditions. Indeed, blood pressure and heart rate monitoring during infusions allows for immediate adjustments when needed. – Early evidence supports oral ketamine’s antidepressant potential, but larger studies with longer follow-up periods are ketamine infusion therapy effectiveness needed to confirm its antisuicidal effects and effectiveness in treatment-resistant depression.

Early reports from street ketamine users showed promise in its antidepressant effects, but they were dismissed because it was an illegal substance. Carly Snyder, MD is a reproductive and perinatal psychiatrist who combines traditional psychiatry with integrative medicine-based treatments. But even though ketamine works quickly, the effects wane after a few days or weeks, research has shown. The use of the drug ketamine has evolved since its development in the 1960s as a human and animal anesthetic.

Therapy Alone Matches Combination Treatment and Outperforms Medication Alone

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.

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.

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.

Until specific research on ketamine-assisted psychotherapy becomes available, clinicians and patients might reasonably consider incorporating psychotherapy into ketamine treatment plans based on these established principles from traditional antidepressant research. As an independent individual without institutional access to research databases or the financial resources to purchase paywalled studies, I have relied on publicly available sources. Some of the studies included here were only available as abstracts, meaning I did not have access to the full text. In many cases, these abstracts did not include specific numbers such as absolute response rates or remission rates.

In summary, ketamine should not be used in patients with poorly controlled cardiovascular disease and should be avoided in individuals with certain poorly controlled psychoses (grade B evidence, moderate level of certainty). For hepatic dysfunction, it should be avoided in individuals with severe impairment but may be administered judiciously with proper monitoring in people with moderate disease (grade C evidence, low level of certainty). In patients with elevated intracranial and intraocular pressure, there is grade C evidence that ketamine should not be used or used only in lower dosages with extreme caution (low level of certainty). Serial ketamine infusions should not be undertaken in patients with an active substance abuse problem and should be used along with universal precautions to monitor for abuse (grade C evidence, low level of certainty). In a single double-blind RCT, the effects of IV ketamine (0.15 mg/kg administered over 10 minutes) were investigated in 8 patients with PHN.157 Between 15 and 45 minutes following the ketamine infusion, significant reductions in pain scores were observed compared with placebo.