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LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
LAS VEGAS – Ketamine infusions are a reasonable option for patients with central sensitization pain syndromes, Jay Joshi, MD, said at the annual PAINWeek.
This disparate group of disorders includes pain experienced by both the body and mind: anxiety and depression, complex regional pain syndrome, opioid-induced hyperalgesia, phantom limb pain, fibromyalgia, and PTSD. In trained hands, ketamine infusions can benefit all of them, often providing the first relief for patients frustrated by years of seeking help for a medical disorder that has no obvious physical cause, said Dr. Joshi, CEO and medical director of the National Pain Centers in Vernon Hills, Ill.
Central sensitization is a CNS response to pain, often chronic, that results in increased neural activity or an increased response to stimuli that wouldn’t normally be interpreted as pain. The root causes can be peripheral injury, persistent inflammation, or neural injury.
“Central sensitization is produced by increases in excitability and reduction in inhibitory transmission, which may produce a persistent enhancement of pain sensitivity,” Dr. Joshi said. These changes include increased glutaminergic signaling – the target of ketamine’s action as an N-methyl-D-aspartate (NMDA) receptor blocker.
By blocking glutamate reuptake and increasing it in the synapse, ketamine “resets the hyperalgesia hyperexcitatory pathway that’s been stuck in this ‘on’ position,” Dr. Joshi said in an interview. “As a selective NMDA receptor antagonist, ketamine seems to be binding to a subreceptor that’s responsible for the symptoms that patients with these syndromes experience. Other NMDA receptor antagonists don’t give the same results. By turning off the signal, we’re giving the nervous system a chance to reset” and return to a more normally functioning state.
“Even though these people have had an injury and aren’t functioning normally, they still have normal neural pathways that can perceive sensation correctly,” he added.
Ketamine is only approved as an injectable anesthetic, but has been gaining popularity as a treatment for depression and other psychiatric disorders, as well as pain. Reports have been so positive that the Food and Drug Administration is considering approval of a ketamine-based nasal spray – esketamine – that’s being developed by Johnson & Johnson. The company reported positive phase 3 data during the May meeting of the American Society of Clinical Psychopharmacology.
When paired with an oral antidepressant, and compared with a placebo spray, esketamine significantly increased the number of responders and remitters and decreased relapses. Based on these results, and three other positive phase 3 studies, Johnson & Johnson submitted for FDA approval in September 2018.
Anecdotal reports of significant relief of chronic pain associated with ketamine have made pain another attractive off-label use, despite a paucity of high-quality data. In July 2018, a consortium of the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published evidence-based guidelines for the drug’s use in chronic pain (Reg Anesth Pain Med. 2018 Jul;43[5]:521-46). Overall, the panel found weak evidence supporting its use for most conditions, except for moderate evidence for complex regional pain syndrome.
- Spinal cord injury pain: Weak evidence for short-term benefit at doses of 0.42-0.4 mg/kg per hour ranging from 17 minutes to 5 hours for 7 consecutive days.
- Complex regional pain syndrome: Moderate evidence for pain improvement up to 12 weeks at doses of 22 mg/hour for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days.
- Mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain: weak to no evidence.
Nevertheless, Dr. Joshi is a firm believer in ketamine’s benefit for pain patients, when it’s administered at appropriate doses by clinicians trained in anesthesia. “Our main clinic is in a surgical center and we administer ketamine under a surgical protocol. This is a powerful anesthetic and should be treated as such,” he said. Patients are risk-stratified with the Anesthesiology Society of America physical status classification system and constantly monitored during the infusions.
These kinds of precautions are not generally taken in the dozens of unregulated “ketamine clinics” continue to open across the country, Dr. Joshi said. “They’re typically not staffed by anesthesiologists or nurse anesthetists, but by other providers without adequate training who may have only taken a weekend or online course in how to administer the drug.”
Dr. Joshi reported no disclosures relevant to his presentation.
EXPERT ANALYSIS FROM PAINWEEK 2018