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Ketamine Guidelines, Administration and the Link Between Pain and Depression

This is a summary of 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 July 2018.

This is the first time that a multidisciplinary consortium of experts have published consensus guidelines due to the variations that exist utilizing ketamine infusions for acute and chronic pain.

The recent surge in opioid use has led to an opiate epidemic that has never been before in the USA. There has been a significant increase in opiate-related deaths in the last 10 years.

To combat this, we have seen a rise in non-opioid based treatment options. Many experts consider the distinction between different pain types to be a continuum, rather than discrete classification categories. Although there is a multitude of evidence supporting analgesic effects for ketamine in peripheral neuropathic and central pain models, there are also studies demonstrating benefit in inflammatory and other non-neuropathic situations. Ketamine exerts its analgesic, antidepressant and psychomimetic effects via multiple pathways. The main mechanism of action is as a non-competitive antagonist of the NMDA receptors in the central nervous system. In high doses, ketamine also activates a variety of opioid receptors, nicotinic, muscarinic cholinergic, and dopaminergic receptors in addition to GABA pathways. The mood-enhancing effects of Ketamine appear to emerge in approximately 4 hours after most of the drug has been cleared from the circulation, and persists for approximately 2 weeks.

There are no published guidelines or recommendations outlining the specific training requirements for physicians involved in the administration of ketamine at dosages above those typically given for depression (>0.5 mg/kg), although its classification as an anesthetic agent has resulted in some institutions mandating that boluses be given only by anesthesiologists or anesthetists. It has been suggested that credentialing in moderate (conscious) sedation should be a prerequisite for staff administering ketamine and the health care providers involved in caring for patients. Staff and clinicians overseeing the care of patients receiving this medication should be trained in responding to cardiovascular and respiratory emergencies. Health care providers involved in the administration of ketamine should also have adequate training in titrating the dose of ketamine while ensuring the safety of the recipient and the availability of treatments to address adverse effects. Furthermore, it is also recommended that ketamine infusions should be performed in settings with appropriate monitoring and resuscitation facilities under the care of an appropriately trained physician.

Individuals respond with great variability to ketamine, so there is a 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.

There is considerable overlap between chronic pain and depression, in terms of coprevalence and treatment. A treatment that intersects with both conditions is ketamine. Systematic and evidence-based reviews have found ketamine to be effective for both chronic pain and depression, and recently there has been a significant surge of interest. As ketamine is classified by most pharmacological sources as an ‘anesthetic agent,’ most hospitals prohibit its use as a ‘bolus’ by non-anesthesiologists.

Is there a link between Pain and Depression? Pain and depression are closely related. Depression can cause pain — and pain can cause depression. Sometimes pain and depression create a vicious cycle in which pain worsens symptoms of depression, and then the resulting depression worsens feelings of pain. Pain and the problems it causes can wear you down over time and affect your mood. Chronic pain causes a number of problems that can lead to depression, such as trouble sleeping and stress.

Disabling pain can cause low self-esteem due to work or financial issues or the inability to participate in social activities and hobbies.

Depression doesn’t just occur with pain resulting from an injury. It’s also common in people who have pain linked to a health condition such as diabetes, cancer or heart disease.

Researchers once thought the relationship between pain, anxiety, and depression resulted mainly from psychological rather than biological factors. Chronic pain is depressing, and likewise, major depression may feel physically painful. But as researchers have learned more about how the brain works, and how the nervous system interacts with other parts of the body, they have discovered that pain shares some biological mechanisms with anxiety and depression.

The overlap of anxiety, depression, and pain is particularly evident in chronic and sometimes disabling pain syndromes such as fibromyalgia, irritable bowel syndrome, low back pain, headaches, and nerve pain. Psychiatric disorders not only contribute to pain intensity but also to increased risk of disability.

There are research studies which shed light on possible improved treatments for chronic pain and sets the foundation to test whether ketamine may play a role in improving the quality of life of certain patients. They have demonstrated that low doses can produce significant and long-lasting effects in depression-like behaviors. Ketamine, which may produce enduring antidepressant effects in humans, has been in clinical use for more than three decades in the United States, and more than 50 years in Europe.

A LARGE population of patients experiences chronic pain and depression or symptoms of depression. How these two syndromes coexist, interact, reinforce each other, and/or are maintained is poorly understood. It is not known whether pain itself can directly cause depression; if so, whether depression or its symptoms start concurrently with pain or develop while pain is perpetuated is not clear. Is it possible that the treatment of a depressive mood is sufficient to allow patients in chronic pain to return to normal activities and enjoy activities that used to make them happy?

With the very complex link between Chronic Pain and Depression, there are multiple avenues of treatment. At StrIVeMD Wellness and Ketamine, we are the experts in delivering safe and monitored care during infusions with IV Ketamine. We are a team of physician anesthesiologists and neurologists that hold the utmost expertise in managing your wellness.

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