Ketamine for neuropathic pain and fibromyalgia has become a hot topic among patients and clinicians. Chronic neuropathic pain and fibromyalgia can feel like an endless loop of discomfort, fatigue, and frustration.
Many conventional pain medicines and antidepressants fall short, leaving people searching for alternatives. Ketamine, a decades‑old anesthetic now being explored at sub-anesthetic doses, has emerged as a potential option when other treatments fail.
This article unpacks how neuropathic pain works, why fibromyalgia is so challenging, the science behind ketamine therapy, evidence for its use, dosing considerations, and patient‑selection guidelines.
By the end, you’ll understand the promise and limitations of ketamine therapy and how it fits into a comprehensive pain‑management plan.
Understanding Neuropathic Pain and Fibromyalgia
How Ketamine Works: More Than an Anesthetic
Evidence for Ketamine in Neuropathic Pain
Evidence for Ketamine in Fibromyalgia
Dosing, Duration, and Treatment Protocols
Patient Selection and Considerations
Benefits and Risks: A Balanced View
Practical Considerations and Holistic Care
Conclusion: A Promising but Cautious Option
Neuropathic pain arises from damage or dysfunction within the nerves themselves. Unlike nociceptive pain, which results from tissue injury, neuropathic pain is caused by a lesion or disease of the somatosensory nervous system.
Patients often describe sensations of burning, pricking, squeezing, or electric shocks. The pathophysiology is complex: injured nerves generate ectopic impulses, sodium and calcium channels become dysregulated, spinal cord neurons become hyperexcitable, and glial cells release inflammatory mediators.
Peripheral nerve injury can lead to central sensitization, a process in which repeated pain input “winds up” the spinal cord, so innocuous stimuli trigger pain. These changes make neuropathic pain notoriously difficult to treat.
Fibromyalgia is a common chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive difficulties. It is classified as a nociplastic pain condition – pain without clear tissue damage or nerve lesion but with disordered pain processing.
Estimates suggest that fibromyalgia affects 1–5 % of the U.S. population, and up to 90 % of those affected are women. Central sensitization is thought to play a major role: the nervous system becomes stuck in a high‑reactivity state, lowering the threshold for pain.
Small‑fiber neuropathy and neuroinflammation may also contribute. Because fibromyalgia overlaps with conditions like depression and anxiety, many patients suffer both physical and emotional distress.
First‑line treatments for neuropathic pain include anticonvulsants (gabapentinoids), tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors, topical lidocaine, and opioids.
For fibromyalgia, exercise, cognitive behavioral therapy, and medications such as duloxetine or milnacipran are standard. Unfortunately, these therapies provide incomplete relief for many.
One study noted that more than 60 % of patients with fibromyalgia or neuropathic pain respond poorly to conventional treatments. Consequently, researchers have explored agents that target central sensitization and neuroplasticity — ketamine being one of the most promising.
Ketamine is a dissociative anesthetic that was first approved for surgical use in the 1960s. At the low doses used for chronic pain, ketamine acts primarily as a non‑competitive antagonist of the N‑Methyl‑D‑Aspartate (NMDA) receptor, a glutamate receptor involved in pain transmission and synaptic plasticity.
Blocking NMDA receptors reduces calcium influx and dampens excitatory glutamatergic activity, thereby interrupting the wind‑up process and decreasing central sensitization.
Ketamine also interacts with opioid, cholinergic, and monoaminergic receptors and may release endogenous opioids. Importantly, ketamine increases brain‑derived neurotrophic factor (BDNF) and enhances synaptic connectivity, supporting neuroplasticity. These actions allow ketamine to “reset” overactive pain pathways.
Unlike standard analgesics, ketamine exerts rapid mood‑modulating effects. Research in patients with depression comorbid with neuropathic pain shows that six low‑dose infusions can yield a response in 68 % of participants and remission in 50.5 %.
Ketamine’s antidepressant effect may result from enhanced glutamate transmission through AMPA receptors and increased synaptogenesis.
Because mood disorders amplify pain, ketamine’s dual action on pain and mood makes it particularly attractive for patients with fibromyalgia or neuropathic pain accompanied by depression or anxiety.
Ketamine therapy is delivered in several forms:
Regardless of the form, ketamine therapy should be administered by trained professionals in a controlled environment, with monitoring of vital signs and mental state to manage dissociation and cardiovascular changes.
A 2022 systematic review and meta‑analysis analyzed randomized controlled trials of ketamine for various neuropathic pain conditions.
Doses ranged from 0.5 to 1.5 mg/kg per day over up to ten days, and pain reduction of 28–46 % was observed, lasting up to two months post‑treatment.
While the heterogeneity of protocols limited firm conclusions, the results indicate that ketamine can provide meaningful relief for some patients.
Side effects were mainly transient psychedelic experiences; with appropriate monitoring, these were manageable.
Researchers have developed standardized low‑dose protocols to improve safety.
A study of a standardized 5‑day infusion of 0.5 mg/kg over 40 minutes for chronic refractory pain (including patients with neuropathic pain and fibromyalgia) reported an 86 % completion rate and significant improvements in pain scores.
The authors stressed the need for standardized approaches and noted that many patients who had failed conventional treatments found relief.
A case report described a patient with chemotherapy‑induced peripheral neuropathy and central sensitization who received multiday sub-anesthetic ketamine infusions.
The therapy led to long‑term improvement in pain and function, suggesting a common mechanism across nociplastic pain conditions.
On patient‑support forums, individuals describe variable responses: some experience near‑complete remission of fibromyalgia symptoms, while others report short‑term relief followed by relapse.
This variability underscores the importance of individualized dosing and monitoring.
Clinical evidence also indicates that ketamine reduces opioid requirements. Studies in chronic pain patients show that ketamine infusions enable significant decreases in opioid use. Ketamine’s promotion of neuroplasticity and reduction of neuroinflammation may support longer‑term improvements, although more research is needed to determine how long benefits persist.
A 2024 systematic review evaluated ketamine therapy specifically for fibromyalgia. Only six small studies (totaling 115 participants) were available, reflecting the early stage of research.
Doses ranged from 0.1 to 0.5 mg/kg administered intravenously or subcutaneously. Short‑term improvement in pain scores was seen in most studies, with pre‑treatment visual analog scale (VAS) scores of 59–100 mm dropping to 2–95 mm after treatment.
Side effects such as dissociation, dizziness, and altered hearing occurred in 71–91 % of participants but resolved quickly after infusion.
The review concluded that ketamine appears effective and safe for short‑term relief but emphasized the need for long‑term data.
A recent case report detailed maintenance IV ketamine therapy for a 60‑year‑old woman with fibromyalgia. The initial nine sessions began at 50 mg (0.8 mg/kg/hr) and were titrated up to 240 mg at 1.5 mg/kg/hr.
After this induction series, the patient experienced >50 % pain relief and transitioned to monthly maintenance infusions at 4.8 mg/kg/hr.
The authors suggested that higher total doses and longer durations might be necessary for maximal benefit.
However, the single‑case nature of the report limits generalisability.
Clinics specializing in ketamine therapy share patient stories highlighting the dual benefits of pain relief and mood elevation.
For instance, one clinic reported that a patient with decades of back pain discontinued opioids after initiating ketamine infusion therapy and described ketamine as “the most helpful pain treatment I’ve ever tried”.
Another patient’s narrative emphasized how the infusion environment and supportive staff contributed to positive outcomes.
These stories echo what many patients on forums express: ketamine can offer hope, but responses vary widely.
Because there is no universally accepted protocol, clinicians tailor dosing based on condition, response, and tolerability. For chronic neuropathic pain, common starting doses include:
For fibromyalgia specifically, doses in clinical studies range from 0.1 to 0.5 mg/kg. The maintenance case report titrated from 50 mg to 240 mg per session.
Some clinics use a series of 6–9 infusions over two weeks, followed by maintenance sessions every one to three months.
Oral troches or nasal sprays may be prescribed for at‑home maintenance under supervision.
Ketamine’s analgesic effects typically last days to weeks. In the meta‑analysis, reductions in pain persisted up to two months after treatment. However, many patients require ongoing maintenance infusions to sustain relief.
Over time, some individuals may develop tolerance, necessitating higher doses or shorter intervals between infusions. Others experience diminishing returns after several cycles.
Thus, patients and clinicians must balance benefits with potential risks.
Ketamine infusions require careful monitoring. During treatment, clinicians track heart rate, blood pressure, oxygen saturation, and level of consciousness.
Side effects include transient elevation in blood pressure and heart rate, nausea, dizziness, visual or auditory changes, and feelings of dissociation.
Severe psychiatric reactions, although rare, are more likely in people with a history of psychosis or substance misuse.
Guidelines advise against ketamine therapy in individuals with uncontrolled hypertension, cardiovascular disease, elevated intracranial pressure, severe liver disease, or active psychosis.
Patients should avoid driving or operating machinery until the day after treatment.
Ketamine therapy is generally reserved for patients with chronic neuropathic pain or fibromyalgia who have not responded to conventional medications and non‑pharmacologic therapies.
Candidates often exhibit central sensitization, small‑fiber neuropathy, or co‑morbid depression. Because ketamine also improves mood, individuals with significant depressive or anxiety symptoms may derive additional benefit.
Some clinicians screen patients using validated questionnaires to identify those most likely to respond.
A comprehensive evaluation should include medical history, medication review, and assessment of psychiatric status. Baseline pain scores and functional measures are recorded.
Patients should discuss potential benefits and risks, and set realistic goals — relief rather than cure. At some clinics, a test dose is given to gauge individual sensitivity before starting a full series.
Because ketamine may evoke dissociative experiences or surface unresolved emotions, integrating psychological support can enhance outcomes.
Some programs offer ketamine‑assisted psychotherapy, where a trained therapist guides the experience and helps patients integrate insights afterward.
For home‑based troche use, telehealth counseling can provide similar support.
Long‑term data on ketamine therapy for pain are scarce. Small studies suggest benefits can persist for months; however, the possibility of tolerance, cognitive effects, or urinary symptoms with repeated exposure remains uncertain.
Ongoing research and registries will clarify these issues.
Ketamine should be integrated into a comprehensive pain‑management plan, not viewed as a standalone cure.
Evidence‑based non‑pharmacologic therapies — graded exercise, mindfulness, cognitive behavioral therapy (CBT), sleep optimization, and anti‑inflammatory diets — remain cornerstones of chronic pain care.
Patients may benefit from physical therapy to improve mobility and psychological therapy to address stress, trauma, or maladaptive coping.
Some clinics combine ketamine with psychedelic integration therapy or ketamine‑assisted psychotherapy to help patients process experiences and maintain behavioral change.
Supplements like NAD⁺ and vitamin B12, which are available through telehealth services, may support energy and recovery when used appropriately.
Ketamine therapy may provide rapid relief, but it is not a cure. Pain reduction typically lasts weeks, not years, and maintenance sessions may be necessary.
Not everyone responds, and side effects can be unpleasant. Patients should weigh costs, logistics, and potential benefits.
Open communication with healthcare providers is crucial to adjust dosing schedules or discontinue treatment if benefits wane.
Telehealth models allow for monitoring and prescription adjustments without frequent clinic visits; for example, at‑home ketamine troches can be delivered by mail through licensed compounding pharmacies.
Why hasn’t my doctor offered ketamine?
Ketamine remains off‑label for most chronic pain indications. Many providers hesitate due to limited long‑term data and regulatory complexity. Seeking a second opinion or consulting a clinic specializing in ketamine therapy can help.
Will I become addicted?
At therapeutic doses, ketamine has a low risk of addiction, especially under medical supervision. Patients are typically not given take‑home injections until safety is established. However, individuals with a history of substance misuse should approach ketamine cautiously and incorporate psychological support.
What are the long‑term consequences?
Research is ongoing. Some patients maintain improvement for months, while others require periodic maintenance. Long‑term safety data are limited, so clinicians monitor cognitive and urinary function. Because of this uncertainty, ketamine is generally used when other treatments have failed.
Ketamine therapy offers hope to people with treatment‑resistant neuropathic pain and fibromyalgia. Its unique mechanism — blocking NMDA receptors and promoting neuroplasticity — allows it to dampen central sensitization and relieve pain when standard therapies fail.
Evidence from randomized trials, systematic reviews, and case reports suggests meaningful short‑term relief and improvements in mood. However, the research base is small, protocols vary widely, and long‑term outcomes remain unclear.
Ketamine is not a cure and should be viewed as one component of a holistic, multimodal pain‑management strategy.
Careful patient selection, dosing, monitoring, and integration with psychological and physical therapies are vital to maximize benefits while minimizing risks.
Chronic pain and fibromyalgia can feel overwhelming, but you don’t have to navigate them alone.
If you’re curious about ketamine therapy or other innovative treatments, Daytryp RX offers telehealth consultations and personalized medication programs.
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