Fibromyalgia is a complex disorder consisting of multiple components which is characterized by chronic pain, fatigue, insomnia, mood, and memory disturbances. Fibromyalgia is the third most common musculoskeletal disorder with increasing prevalence with older age, affecting approximately 3-4% of women and 0.5% of men in the United States. Many elements are involved in the cause of fibromyalgia including genetic, inflammatory, hormonal, and psychological factors. Symptoms may start after a traumatic event, infection, physiologic insult such as surgery, or even after an emotional psychological stressor. Other times, symptoms start after no known cause or trigger.
The thought is that fibromyalgia involves abnormalities of how external stimuli is processed, with increased sensitivity caused by dysregulation of mechanisms that normally regulate pain. More specifically, activation of the N-methyl-d-aspartate receptor (NMDAR) results in increased sensitivity of the spinal cord and brain to pain. The complexity of its pathogenesis and the multiple factors that are involved with fibromyalgia lead to the need for a multi-modality approach to treatment.
It’s important that we understand this specific receptor and its role in fibromyalgia, so let’s briefly review the science. This NMDA receptor is found on ion channels throughout the body including the spinal cord and brain. Glutamate, which is found at increased levels in patients with fibromyalgia, binds to the receptor causing it to become activated. Once activated, ion channels open and allow for entry of sodium and calcium into a cell such as those on the spinal cord and brain causing downstream effects that mediate sensory input and the perception of pain.
Low-dose ketamine, as used for infusion therapy has been shown to have clinical benefit with patients with fibromyalgia. Patients with fibromyalgia are found to have increased sensitivity to the NMDA receptor, thus this has been a target for therapeutic intervention. Ketamine acts as an NMDA receptor antagonist. This means that when ketamine binds to the receptor it prevents opening of ion channels and flow of cations (Ca+, Na+) into cells of the spinal cord and brain, blocking downstream effects such as those involved in the hypersensitivity to pain as seen in patients with fibromyalgia. Additionally, ketamine has been known to have anti-inflammatory effects, with inflammation believing to play a big role in the pathogenesis of fibromyalgia.
In a double-blind, placebo-controlled study patients with fibromyalgia received a single dose of ketamine infusion (0.3 mg/kg), patients experienced a significant reduction (>50%) in pain intensity scores. The majority of patients treated with ketamine reported a significant decrease in tenderness, increased muscle endurance, decreased pain threshold, and pain tolerance at tender points.
Research shows that longer infusions may be required for longer-lasting relief of chronic pain syndromes such as fibromyalgia. These studies indicate that the effect of ketamine in longer duration protocols persist for at least 4 weeks versus shorter duration infusions which could have shorter pain alleviation lasting from days to weeks, indicating that re-treatment may be required within 4–6 weeks following the initial treatment period. Based on the research, our protocol includes a starting dose of 0.5mg/kg of body weight for 90 minutes for 6 infusions over a course of 3-6 weeks. We titrate/increase the dose based on patients’ response and tolerance.
Fibromyalgia is a complex disorder causing many different symptoms via several mechanisms that affect a large number of people in the US. Ketamine has been found to be an effective and safe treatment option for patients with fibromyalgia through various mechanisms. While typical durations of infusions, such as those used to treat depression have positive results, longer infusions appear to provide the most long-lasting relief of pain and symptoms.
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