Ketamine Treatment Options

This preclinical phase 1 development study in healthy volunteers seeks to identify if low doses of commonly used non-triggering anesthetic agents might have clinical utility for modulating emotional memory processing and to understand the nature of the brain mechanisms of drug action. Optimally, a drug, dose and brain mechanism of action will be identified that will form the foundation for future use in clinical studies of patients with PTSD. Read Less

In a healthy patient, the lungs provide oxygen to the blood and remove carbon dioxide. However, in patients with severe lung failure, blood may not adequately be delivered to the lungs, or the lungs may not adequately supply blood with oxygen. In this case, patients may require assistance from a machine to help provide this oxygen. Extracorporeal membrane oxygenation (ECMO) is a device that acts as an artificial lung, allowing the patient to recover from their illness. Patients receiving support from ECMO are often put in a medically induced coma while their lungs heal. Certain drugs may stick to the internal surfaces of the machine; therefore leading to decreased concentrations. Patients receiving ECMO often require high doses of both pain medications and sedatives in order to provide comfort. Low doses of a drug, ketamine, may help to provide additive effects to pain relief and allow lower doses of other pain medications. The hypothesis is that patients treated with continuous intravenous ketamine, will have lower requirements of other pain medications while receiving ECMO for acute respiratory failure while achieving the desired level of sedation. Read Less

The objective of the current program of research will be to test whether intranasal ketamine treatment is more effective than placebo in reducing suicidal ideation in suicidal patients presenting for acute treatment in emergency department settings. Secondary objectives will test the effect of genotypic differences in the mu opioid receptor on efficacy of ketamine and the correlation of speech patterns and facial movement patterns with subjective reductions in suicidal ideation after ketamine treatment. Read Less

This study is testing drugs not previously used topically for the treatment of vulvodynia, a common genital pain syndrome. It is hoped that one of these drugs will improve vaginal entryway pain with touch, daily pain scores and sexual functioning. Read Less

Ketamine is an IV anesthetic with non-opioid analgesic properties that has been shown to reduce pain while also decreasing intraoperative and postoperative opioid requirements when used in subanesthetic doses after a variety of surgical procedures.1 It is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, and by this mechanism ketamine is believed to block the development of central sensitization and wind-up phenomenon,2,3 which may be helpful in preventing acute and chronic pain after repetitive insults. In a systematic review of ketamine as an adjuvant to opioid analgesia, low-dose ketamine was found to be a useful addition to standard postoperative pain management practice with opioids in 54% of studies.1 The studies that did not show a significant effect were in patient populations with low opioid requirements. Therefore, it has been suggested that future clinical trials be focused on patient populations with significant post-operative pain, such as spine surgery and major orthopedic surgery not amenable to regional analgesia, and postoperative pain in patients on chronic preoperative opioid therapy.1 There are few studies examining outcomes after ketamine in the perioperative period after spine surgery. Loftus et al randomized patients with a history of chronic preoperative opioid use (i.e., daily opiate use for at least 6 weeks) to intraoperative ketamine versus placebo and found a 30% reduction in morphine consumption at 48 hours and an approximately 25% reduction in visual analog scale (VAS) pain score in the post anesthesia care unit and at 6 weeks.4 Although this study provided evidence that there may be reduction in long-term postoperative pain, additional studies are needed to provide evidence that this effect is sustained beyond the 6-week period. We are interested in examining ketamine more closely in spine surgery because this patient population experiences significant postoperative pain that may be difficult to control due to preoperative opioid use (i.e., opioid tolerance). The investigators chose to study ACDF patients specifically because it is a common spine procedure throughout the United States and the patients have significant opioid requirements postoperatively. In a study examining the effects of the low dose ketamine for postoperative IV PCA fentanyl after cervical and lumbar surgery, patients in the placebo group (and thus only receiving fentanyl PCA) reported mean VAS scores of 4-5 with movement while receiving opioids.5 Further, while previous studies have shown an opioid-sparing effect of ketamine as measured by opioid consumption and a decrease in pain as measured by VAS scores, no study to our knowledge has examined quality of recovery after intraoperative ketamine infusion. The Quality of recovery (QoR-40) score was developed by Myles et al to assess quality of recovery after anesthesia based on forty questions in five dimensions,6 and this score has been shown to be a reliable and valid outcome for patients undergoing both spine and cranial surgery.7 QoR-40 is also of interest because it should be able to provide a global assessment of the possible benefit or harm of using ketamine in patients by simultaneously characterizing the detrimental side effects as well as the positive benefits of ketamine when used as an infusion at subanesthetic levels (studies thus far have shown that there are minimal side effects such as hallucinations).1,4 Significance: Previous studies have shown an opioid-sparing effect of ketamine, however further research is warranted in patients whose pain may be difficult to control and whether this effect is sustained. ACDF patients experience significant pain post-operatively, and ketamine may improve their quality of recovery due to its opioid-sparing effects and prevention of chronic pain. Further, patient centered outcomes as measured by the QoR-40 have not been reported in the literature when ketamine, or other opioid sparing anesthetics, have been administered. This study will not only determine if the "moderate" dose of ketamine is beneficial or detrimental to the recovery of patients but also whether it can improve long term patient function, presumably by decreasing central pain sensitization. In addition, this study will set the stage for further RCT's examining other analgesic strategies in cervical spine surgery patients (i.e., intraoperative lidocaine infusions, volatile anesthetic vs. propofol as the primary hypnotic, COX-2 inhibitors, pregabalin, etc.). The overall goal would be to develop a multi-faceted regimen that decreases the postoperative inpatient opioid requirements of these patients and may facilitate long term recovery. The research questions:Does ketamine improve the quality of recovery at 24 hours after anterior cervical discectomy and fusion (ACDF)? The hypothesis: the investigators hypothesize that ketamine will improve the quality of recovery after ACDF surgery Read Less

Background: The poor prognosis and public health burden of PTSD necessitates the development of more effective and broader treatment approaches. In the etiopathogenesis of PTSD, trauma memories become ingrained into key brain areas through conditioned learning and are triggered by various situations of daily life. The brain glutamate system plays a key role in the process of trauma learning and trauma memories via long-term potentiation. Ketamine administration modulates the glutamate system and has been used in the treatment of depression and PTSD. Previous studies demonstrate that a single low dose of ketamine rapidly improves symptoms of refractory PTSD and treatment resistant depression. Unfortunately the observed response is short-lived (4-7 days, maximum up to 2 weeks) and multiple doses often produce unacceptable side effects. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation for trauma memory) psychotherapy, is a manualized and translational mindfulness based cognitive behavioral therapy specifically designed to target trauma memories and their expressions in PTSD patients. The placebo controlled pilot study examined the efficacy of a protocol combining a single infusion of low dose ketamine (0.5mg/kg) and TIMBER psychotherapy in subjects suffering from chronic PTSD. The objective of this pilot study was to optimize and individualize treatment of chronic PTSD using a rapid, effective, trauma specific, user friendly and inexpensive approach that uses cutting edge psychopharmacological combined with novel psychotherapeutic approaches. Methodology: The randomized, double blind, placebo-controlled pilot study used a crossover design. Ten subjects with refractory PTSD were assigned to one of two arms: one arm (n=5) received combined ketamine infusion and TIMBER therapy (TIMBER-K arm) and the second (n=5) received combined placebo (normal saline) infusion and TIMBER therapy (TIMBER-P arm). All 10 subjects received a short version of TIMBER therapy after 10 minutes of onset of the infusion in which reactivation of trauma memories was initiated in a controlled manner using standardized scales and scripted narrative of the index trauma. This was followed by a standardized mindfulness based cognitive therapy module to quickly de-escalate the arousal symptoms followed by induction of detached observation and reappraisal of the trauma experience. After completion of the 40-min infusion, all subjects were trained on the full version of TIMBER therapy using methods of mindfulness based graded exposure therapy and a twice-daily schedule of home practice was initiated. The investigators are currently in a process of recruiting fifty more subjects to examine the effects in a larger sample. Read Less

The purpose of this study is to test whether ketamine and D-cycloserine can be safely and effectively used for the treatment of depression. The investigators hypothesize that ketamine will serve as a rapid acting and safe antidepressant in patients with bipolar depression, and furthermore, that D-cycloserine will serve as an effective therapy following ketamine treatment. Read Less

To evaluate the safety and effectiveness of Wafermine administered with and without an opioid medication for acute pain following bunionectomy surgery. Read Less

This study investigates the common features of electrophysiological measures in schizophrenia and effects of NMDA antagonist ketamine in healthy volunteers. Read Less

Dosing of medications is based on the plasma level achieved with a given dose and how long the medicine remains in the body. This study is called pharmacokinetics-that is, what the body does to the medication. Ketamine is an intravenous medication used for anesthesia and sedation in children. However the pharmacokinetics of Ketamine has not been systematically studied. We propose to study the pharmacokinetics of ketamine in different age groups of children ranging from infants to teenagers. Read Less

The primary objectives of the study are to evaluate the efficacy of subdissociative dose intravenous ketamine compared with intravenous morphine in relieving acute pain in the ED. Secondary objectives will include the rate of adverse effects and need for rescue analgesia. The hypothesis is that intravenous administration of subdissociative dose ketamine at 0.3 mg/kg is superior to intravenous morphine at 0.1mg/kg in treating moderate and severe acute pain in patients presenting to the ED. Read Less

Depression is common in patients with cancer. Current medications for depression, while effective, take several weeks to take effect. Ketamine has emerged as a drug with promise for cancer patients. In two reported cases, a single dose of ketamine induced rapid and moderately sustained symptom reduction in depression and anxiety with no adverse side effects. Benefit was seen in as little as 1 hour and sustained up to 30 days. This study is a randomized, double-blind, placebo-controlled investigation testing whether a single dose of ketamine improves depression and anxiety relative to placebo in patients with cancer. Read Less