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Ketamine is an FDA approved anesthetic used daily throughout the United States. Used in subanesthetic dosing, ketamine is known to provide profound pain relief even when patients are taking large doses of opiates.
Ketamine acts very differently than opiates, blocking NMDA receptors. Ketamine is used off label to help treat mood disorders like depression and anxiety.
We’ve discovered that chronic pain is a systemic disease with multiorgan effects. The most significant of these changes occur in brain and spinal cord. Providers have discovered that treating the depression and anxiety that affect 60-85% of patients is critical to long term recovery.
While it makes sense that depression and chronic pain so often affect the same individual, chronic pain induces wide spread changes in brain function that can be visualized on specialized MRI’s. There are complex neurobiological changes occurring in the brain that make patients more resistant to treatment. These changes reflect plasticity or ability of the brain to change and part of a process called central sensitization.
Central sensitization is a process where the central nervous system (brain and spinal cord) becomes overly sensitive and reactive to stimuli, leading to pain hypersensitivity. It essentially involves the CNS amplifying pain signals, making them feel more intense and widespread. This heightened sensitivity can be triggered by various factors and is often associated with chronic pain conditions.
We also now understand that not only depression is a product of these changes, depression also reinforces a negative feedback loop.
Typically, patient’s in severe pain are offered opiates. Unfortunately opiates have several drawbacks that make them less than desirable as long term treatment option.
A critical feature of all opiates is the development of tolerance. Overtime, larger doses are needed to maintain the same drug effect.
Multiple studies now show that opiates are associated with worsening depression and anxiety.
And of course, the inherent risk of addiction make opiates challenging.
Ketamine is very well suited to treatment of chronic pain because it not only helps the mechanical problem as well as the mood component as well.
Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders: A Multivariable Mendelian Randomization Analysis. JAMA Psychiatry. 2021;78(2):151–160
Fibromyalgia syndrome (FMS) is a common disease characterized by chronic, persistent, and widespread pain associated with fatigue, sleep disturbance, irritable bowel syndrome (IBS), impaired cognitive and physical function, and depression.
The etiology and pathophysiology of fibromyalgia (FM) remain unclear despite extensive research. FM can be treated by various approaches including both pharmacological and non-pharmacological treatments including cognitive behavioral therapy, exercise programs, recreational activities and sleep hygiene.
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Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. CRPS is a clinical disorder defined by the International Association for the Study of Pain (IASP) as “a syndrome characterized by a continuing regional pain that is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion”.
Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended.
The effect of ketamine infusion in the treatment of complex regional pain syndrome: a systemic review and meta-analysis. Curr Pain Headache Rep. 2018; 22: 12.
The most prominent rationale to use ketamine in CRPS patients is that NMDA receptor in the spinal cord plays an important role in the wind-up phenomenon and central sensitization. The analgesic effects of ketamine can most likely be attributed to prolonged NMDA receptor desensitization, which counteract central sensitization at spinal and supraspinal sites.
Ketamine treatment can provide clinically meaningful pain relief, series or treatment may provider for up to 3 months of relief.
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. Reg Anesth Pain Med. 2018;43:521–46.
N-methyl-D-aspartate receptor open-channel blockers memantine and magnesium modulate nociceptive trigeminovascular neurotransmission in rats. Eur J Neurosci. 2019;50:2847–59.
Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2019;129:241–54.
It can be hard to imagine a headache that lasts for days and entirely disrupts your daily life. According to the Migraine Research Foundation, around one in four U.S. households has a member suffering from debilitating headaches.
Libertas Mind offers specialized outpatient infusions to treat pain including migraines. Ketamine, an off-label treatment for depression, is emerging as an important medication in this regard because of its NMDA receptor antagonism.
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. Reg Anesth Pain Med. 2018;43:521–46.
N-methyl-D-aspartate receptor open-channel blockers memantine and magnesium modulate nociceptive trigeminovascular neurotransmission in rats. Eur J Neurosci. 2019;50:2847–59.
Ketamine infusions for chronic pain: a systematic review and meta-analysis of randomized controlled trials. Anesth Analg. 2019;129:241–54.
Ketamine has made a number of headlines recently in regards to migraines.
The Ket Head trial – a multicenter, placebo-controlled, randomized controlled trial – was launched to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion. Participants will be randomized to either ketamine (1 mg. kg−1 bolus followed by infusion of 1 mg. kg−1. h−1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h.
Intranasal (IN) ketamine recently demonstrated strong results in treatment refractory migraine patients who already tried 4 or more medications in multiple classes. Published in Regional Anesthesia & Pain Medicine May of 2023, of the 169 patients followed in their retrospective review, half of the participants found IN ketamine “very effective,” and 40% found it “somewhat effective.” Up to 80% of participants co.ntinue to use IN Ketamine.
Thomas Jefferson University, perhaps an institution with the most experience treating migraines with ketamine published a retrospective study of sixty-one patients who underwent five-day intravenous ketamine therapy sessions in Regional Anesthesia & Pain Medicine 2018. They found 77% success rate, with 40% experiencing sustained relief.
Ketamine’s efficacy for migraines may lay in it’s unique ability to reverse central sensitization. This neurological phenomenon, where repetitive stimulation of a nerve leads to increased excitability , is common in headache disorders.
As more data is reviewed, it seems safe to conclude there is a role for Ketamine in the treatment of intractable migraines. Libertas mind also offer specialized nerve injections – different than Botox- called Sphenopalatine ganglion and Stellate ganglion nerve blocks for migraine relief. Contact Libertas Mind for more information.
Learn more about the different treatment options available.
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