Ketamine Medical Literature
For the past 20 years there has been a steadily growing body of scientific research detailing the efficacy of ketamine in treating a variety of medical problems. A sampling of literature related to the conditions where ketamine has been shown to be of benefit follows below:
Dosage and Timing of Maintenance Infusions
As with most other drugs, there is a dose:response relationship with ketamine. That is why the relatively low doses that Spravato (the nasal form of ketamine) administration delivers requires re-administration once a week at the least, and for many patients twice a week. That is also why the low doses of ketamine administered in clinics that are not staffed by anesthesiologists result in some patients being labeled as “non-responders,” when in fact they would get relief if only a higher dose infusion of ketamine was given.
The higher doses we routinely administer – some even up to 4 or 5 times higher and inducing a light general anesthetic – allow every patient who might respond favorably a chance to do so. That is also why our higher dosing allows longer periods of time to elapse between maintenance treatments, saving patients both money and disruptions in their lives.
- Efficacy of Different Doses of Ketamine as a Bolus in Major Depressive Disorder
- Ketamine’s Dose-Related Effects on Anxiety Symptoms in Patients With Treatment Refractory Anxiety Disorders
- Ketamine Augmentation for Outpatients With Treatment-Resistant Depression: Preliminary Evidence for Two-Step Intravenous Dose Escalation
- A Randomized Trial of an N-methyl-D-asparte Antagonist in Treatment Resistant Depression
- Continuation Phase Intravenous Ketamine in Adults Withh Treatment-Resistant Depression
- Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression
- Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
- Maintenance Ketamine Treatment Produces Long-Term Recovery From Depression
Over the past twenty years, ketamine infusions have been extensively studied for the treatment of medication-resistant depression. Psychiatrists have performed the vast majority of studies, so only very low doses of ketamine have typically been used (0.5 mg/kg given over 40 – 60 minutes). Even at these low doses we can expect approximately 60 - 70% of patients to find relief. However, within 3 weeks of completing the initial course of 6 low-dose infusions, half to three fourths of patients have return of their depression.
Fortunately, anesthesiologists can administer much higher doses of ketamine (as much as 4 - 5 times higher), and some patients who do not respond at the lower dose will fortunately find relief with a more aggressive dosing regimen. In addition, the higher doses that we give allow a considerably longer period of relief, and patients can thereby extend the time period between “maintenance” infusions. This benefits patients both financially as well as being far less disruptive to their lives.
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders
- Use of Ketamine in Clinical Practice: A Time for Optimism and Caution
- Ketamine: A Paradigm Shift For Depression Research and Treatment
- Ketamine for the Treatment of Major Depressive Disorder and Bipolar Depression: A Review of the Medical Literature
- Ketamine for Treatment-Resistant Unipolar and Bipolar Depression: Critical Review and Implications for Clinical Practice
- Antidepressant Effects of Ketamine in Depressed Patients
- Evolving Issues in the Treatment of Depression
- A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders
- Esketamine Nasal Spray Effective in Treatment-Resistant Depression
- Psychiatric Practice Patterns and Barriers to the Adoption of Ketamine
A unique property of ketamine is its ability to dramatically reduce suicidal ideation in many patients after only a single treatment.
- Ketamine as a Potential Treatment for Suicidal Ideation: A Systematic Review of the Literature
- Ketamine as a Rapid-Acting Agent For Suicidal Ideation
- Is Ketamine the New Wonder Drug For Treating Suicide?
- The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
Post-Traumatic Stress Disorder (PTSD)
Ketamine infusions have emerged as a third treatment option (along with anti-depressants and cognitive behavioral therapy) for patients suffering from PTSD. Reduction of PTSD symptoms occurs along with a decrease in depressive symptoms. It is believed that by acting as an NMDA antagonist ketamine is able to favorably alter the neuroplasticity of brain synapses.
- Efficacy of Intravenous Ketamine for Treatment of Chronic Post-traumatic Stress Disorder: A Randomized Clinical Trial
- Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
- Ketamine as a Treatment for Post-traumatic Stress Disorder: A Review
Obsessive-Compulsive Disorder (OCD)
A single dose of ketamine has a beneficial effect on OCD that lasts up to one week. As with other conditions, there is a dose:response relationship, with higher doses of ketamine being more effective than lower doses.
- Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
- Ketamine’s Dose Related Effects on Anxiety Symptoms in Patients With Treatment Refractory Anxiety Disorders
- Obsessive-Compulsive Disorder: Advances in Diagnosis and Treatment
Anesthesiologists have used the analgesic effects of ketamine in anesthetized patients since its introduction in the US in 1970. Postoperative patients typically consume around 25% less narcotics in the first 24 hours after surgery if given ketamine while asleep in the OR. With our current opioid crisis, it appears that ketamine can play a significant role in reducing opioid consumption in chronic pain patients. Most pain patients who experience at least some relief with ketamine infusions are able to decrease their dependence on narcotics, some to a dramatic degree. Ketamine has also found use in ultra-rapid detoxifying of opioid-dependent patients.
- Sustained Opioid Cessation Following Rapid Opioid Detoxification with Ketamine Infusion Therapy in Veterans a Preliminary Study
- The Use of a Sub-Anesthetic Infusion of Intravenous Ketamine to Allow Withdrawal of Medically Prescribed Opioids in People With Chronic Pain, Opioid Tolerance, and Hyperalgesia: Outcome at 6 Months
- Use of Ultra-Rapid Opiate Detoxification in The Treatment of US Military Burn Casualties
- Use of Ketamine in a Multi-Modal Analgesia Setting For Rapid Opioid Tapering in a Profoundly Opioid-Tolerant Patient: A Case Report
- S(+)-Ketamine Attenuates Increases in Electroencephalograph Activity and Amplitude Height of Sensory-Evoked Potentials During Rapid Detoxification
It appears that glutamate receptors are involved in patients suffering from migraine headache, and one mechanism by which ketamine works is by targeting these receptors. Ketamine also exerts its beneficial effects on patients with migraine headache by targeting NMDA receptors.
- Glutamate and Its Receptors as Therapeutic Targets for Migraine
- Intravenous Ketamine for Subacute Treatment of Refractory Chronic Migraine: A Case Series
- Ketamine Infusions for Treatment Refractory Headache
- Ketamine Infusion Combined With Magnesium As a Therapy For Intractable Chronic Cluster Headache: Report of Two Cases
CRPS is recognized as one of the most difficult to treat of all pain conditions due to its having a centralized mechanism. In the lay press it has been labeled the “suicide pain”, as it sometimes leads patients to take their own lives to escape the pain. Ketamine is usually effective in at least reducing the pain of in most patients with CRPS, allowing many to resume a normal life. In treating CRPS, the high doses of ketamine that only anesthesiologists can safely administer are needed to effect relief. In addition, given the overall difficulty in obtaining relief, many times prolonged infusions are required, as well.
- Efficacy of Ketamine in Anesthetic Dosage for the Treatment of Refractory Complex Regional Pain Syndrome: An Open-Label Phase II Study
- The Effect of Ketamine Infusion in Complex Regional Pain Syndrome: A Systemic Review and Meta-Analysis
- Treatment of Complex Regional Pain Syndrome: A Systematic Review and Narrative Synthesis
- Differential Efficacy of Ketamine in the Acute Versus Chronic Stages of Complex Regional Pain Syndrome in Mice
- Ketamine and Chronic Pain: Going the Distance
Neuropathic pain, like CRPS, is usually difficult to treat. However, ketamine has shown to be effective in many patients suffering from this type of pain. Higher total infused dose along with increased duration of infusions are associated with greater pain relief. Like with CRPS, patient expectations should focus on reduction of pain as opposed to total abolition of pain.
- Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization
- Management of Chronic Neuropathic Pain With Methadone Combined With Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial
Recent studies indicate that ketamine infusions may be of benefit in treating patients with fibromyalgia.