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, 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.

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.

Systematic Reviews Cited

Differences not only in disease features but also patient characteristics, and practice settings and capabilities, further highlight the need for dosing flexibility. As is true for all aspects of medicine, the decisions as to when a treatment is indicated, what setting and parameters to use, how to monitor its effects, and how to minimize risks should be made on an individualized basis after sufficient discussion with the patient (Table 6). When used for chronic pain, many physicians will administer the highest dose tolerated in an effort to “reverse central sensitization” or “unwind windup,” attempting to pharmacologically counteract adverse effects, rather than tapering down the infusion.

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.

Adverse effects

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.

• Someone who is suicidal does not have the luxury of waiting several weeks for a medicine to kick in.
• In one study, 85% of patients experienced a remission in their depressive symptoms (defined as at least a 50% reduction in symptoms).
• Clinical studies show that weekly maintenance infusions effectively sustain antidepressant benefits.

Clinical Implications and Conclusions

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 needed to confirm its antisuicidal effects and effectiveness in treatment-resistant depression.

Clinical Trials vs. Systematic Reviews

Always seek the advice of a physician or healthcare provider for any questions you may have regarding a medical condition. Authorities said this week that Perry’s live-in assistant, who had no medical training, injected him with the drug on the day he died. Meta-analyses do the same thing—they combine results from many studies to find the real trend instead of getting distracted by outliers. One small study might suggest a treatment works wonders, but if ten larger studies show it barely helps, a meta-analysis will reveal the truth. It is possible that the full studies contain these missing data points, but without access, I was unable to verify them.

• The findings also give hope to millions of pain sufferers with complex conditions that have not responded to conventional treatment.
• 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).
• Ketamine infusion therapy helps with a number of psychiatric conditions, but it is most commonly used in those with treatment-resistant depression, a form of major depressive disorder.
• – Early evidence supports oral ketamine’s antidepressant potential, but larger studies with longer follow-up periods are needed to confirm its antisuicidal effects and effectiveness in treatment-resistant depression.
• Articles considered for inclusion were animal and experimental studies, systematic and other types of reviews, meta-analyses, clinical trials, and, for certain sections in which high-grade evidence was lacking (eg, treatment, complications), case reports and series.

Impact on depression symptoms over time

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 ketamine infusion therapy effectiveness 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.

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.

Repeated ketamine infusions offer no extra benefit for people hospitalized with depression

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.

How to Find a Provider for Ketamine Infusion Therapy

Protocols from various institutions including academic, private practice, military, and Veterans Administration were also reviewed to gauge community standards. In summary, there is insufficient evidence supporting preinfusion testing prior to the administration of IV ketamine for chronic neuropathic pain conditions in healthy individuals. In individuals at high risk of cardiovascular events or symptoms suggestive of cardiovascular disease, baseline ECG testing may be considered to exclude individuals with uncontrolled ischemic heart disease. In individuals with baseline liver dysfunction, at risk of liver toxicity (eg, alcohol abusers, people with chronic hepatitis), or who are expected to receive high doses of ketamine at frequent intervals, baseline and postinfusion liver function tests should be considered on a case-by-case basis (grade C evidence, low level of certainty). The issue of dosing as it relates to the occurrence of psychomimetic adverse effects is not clearly established in the literature.