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Ketamine is a dissociative anesthetic that has gained attention for treating chronic and neuropathic pain when standard treatments fall short. [1] Used off-label in pain management, ketamine has shown effectiveness in certain conditions, including complex regional pain syndrome (CRPS), fibromyalgia, migraines, and other refractory pain syndromes. [2]
Ketamine’s appeal lies in its rapid pain-relieving properties and its ability to reduce reliance on opioids. However, patients and providers often wonder how long ketamine's pain relief lasts since its benefits can be temporary.
- Many patients experience significant pain reduction for a few days to a couple of weeks after treatment, although relief duration varies by condition and regimen.
- Ketamine blocks N-methyl-D-aspartate (NMDA) receptors in the nervous system, reducing central sensitization (“wind-up” of pain signals) and resetting hyperactive pain pathways. This leads to analgesia even at subanesthetic doses.
- Because relief is temporary for many, patients may undergo a series of infusions or periodic booster treatments. Long-term ketamine use can help in refractory pain but carries risks, like tolerance, bladder issues, and abuse potential.
How ketamine works to relieve pain
Ketamine relieves pain primarily by acting as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors in the brain and spinal cord. [1] These receptors are involved in a process called central sensitization, where ongoing or repeated pain signals make nerves increasingly sensitive, intensifying the sensation of pain. By blocking NMDA receptors, ketamine disrupts this amplification mechanism, reducing nerve sensitivity and easing pain. [1]
Interrupting this cycle can help reset neural pathways, reducing pain intensity and halting the progression of chronic pain. In addition to NMDA, ketamine also influences other receptors (like opioid and AMPA receptors) that modulate pain and mood. At subanesthetic doses (far below those used in surgical anesthesia), ketamine induces significant analgesia without complete loss of consciousness. This unique pharmacology explains why ketamine can alleviate severe pain, even in cases where opioids and other drugs have failed. [3]
Typical duration of ketamine pain relief
Ketamine’s pain-relieving effects are generally short-lived in most cases. Clinical evidence indicates that after an initial ketamine infusion, analgesia often lasts from several hours to a few days and sometimes up to 1–2 weeks. [4] A 2019 meta-analysis of trials found a modest but significant pain reduction persisting for about two weeks post-infusion, as compared to placebo. [4]
Beyond that point, benefits usually diminish as pain gradually returns to baseline. A Canadian review similarly concluded that IV ketamine provides only short-term pain relief in chronic non-cancer pain, and the long-term efficacy remains unclear. [2]
However, the duration of relief varies widely between people. Factors, such as the type of pain-related condition, ketamine dosage, infusion length, and number of sessions, can all influence how long pain is reduced. Generally, longer or repeated infusions produce more durable relief than a one-time short infusion. [1] Many patients experience temporary improvement and often require additional treatments when pain returns.
Analgesic uses of ketamine
Beyond acute pain, ketamine can also be used for chronic pain conditions.
Complex regional pain syndrome
Within cases of complex regional pain syndrome (CRPS), ketamine has shown relatively longer treatment effects. In some studies, intensive infusion protocols (e.g., continuous low-dose infusions over multiple days) have yielded pain relief lasting around 8–12 weeks. [5]
For example, a 10-day series of subanesthetic ketamine infusions led to significantly improved pain for about 3 months in CRPS patients versus placebo. [5]
Fibromyalgia and other chronic pain
In fibromyalgia, diabetic neuropathy, migraines, and most other chronic pain syndromes, ketamine’s benefit is typically short-term. [6] Patients often enjoy relief for only a few days to a couple of weeks following an infusion of ketamine. [4]
After this, pain usually returns, meaning repeat treatments are needed to sustain relief. Some people with severe fibromyalgia or neuropathic pain receive periodic maintenance ketamine infusions (often as monthly boosters) to manage flare-ups. [7]
There are case reports of fibromyalgia patients achieving sustained improvement with ongoing IV ketamine therapy, but such evidence is limited to individual cases. [8] Overall, current research has not established any consistent long-term benefit of ketamine for these conditions beyond the initial short-term pain alleviation. [2] A Cochrane review effort, however, is underway to evaluate ketamine and other NMDA-blockers for chronic pain, reflecting ongoing interest in extending its benefits. [9]
Types of ketamine treatment and their durability
The route of ketamine administration can influence how long pain relief lasts.
Intravenous infusions
Intravenous (IV) ketamine infusions are the most common method used in chronic pain treatment. A single subanesthetic infusion may provide relief for a few days, while a series of infusions (spread over 1–2 weeks) often yields a longer cumulative benefit, sometimes lasting for a few weeks. [4] Longer infusion protocols (often given as multi-day continuous infusions) have led to pain relief lasting for months in certain cases of CRPS. [1] In general, repeated or prolonged infusions confer more durable pain relief. [1]
IV infusions allow for precise dosing and are done under close medical supervision due to ketamine’s psychoactive side effects.
Other routes of administration
Beyond IV administration, ketamine can also be given as a nasal spray, oral troche, injection, or topical cream. These forms are less potent and tend to provide shorter relief.
Intranasal and oral forms
Intranasal and oral ketamine provide fast-acting but short-lived pain relief, typically lasting only a few hours. Often used between infusions, they offer convenience but have lower bioavailability and thus provide less sustained pain control. [1]
Intramuscular injections
Intramuscular injections can treat acute pain flares. Intramuscular ketamine is fast-acting, offering a quick onset of pain relief, but it wears off within hours.
Topical forms
Topical ketamine creams are used for localized nerve pain. They don’t provide any lasting effects and are useful only while applied.
Intrathecal injections
Intrathecal ketamine is delivered straight into the cerebrospinal fluid, blocking pain signals closer to their origin. This route requires much smaller doses than those needed for IV or oral ketamine, reducing the risk of common side effects, such as sedation, hallucinations, or increased heart rate.
Recent work includes a 2024 phase II study showing that intrathecal ketamine used alongside opioids effectively relieved refractory cancer pain, with tolerable side effects and reduced opioid needs. In surgical settings, a 2023 meta-analysis of perioperative ketamine use found that a single small intrathecal dose significantly reduced postoperative pain and opioid consumption.
Considerations for use
The safety of ketamine use is carefully monitored. Yet, accurate, long-term human safety data remain limited, and mild CNS effects (like light sedation) are still reported. It’s often practical to combine approaches, such as an initial IV infusion series for immediate pain reduction, followed by oral or nasal ketamine for breakthrough pain or maintenance between infusions. [10]
Maintenance and long-term use of ketamine infusions
For chronic pain conditions that respond well to ketamine, clinicians may consider maintenance therapy—often given as periodic booster infusions or ongoing low-dose treatments to prolong pain relief. [11] There is no standard frequency for maintenance infusions; some patients might receive ketamine monthly or every few months, while others undergo another shorter series of infusions whenever pain flares. The goal is to preserve the analgesic benefits observed after the initial treatment. [7]
While long-term ketamine may help some patients with refractory pain, high-quality evidence remains limited, with most studies tracking outcomes for only weeks to months. Still, some individuals report lasting relief with carefully spaced infusions. [2] Many studies follow patients only for weeks to a few months. Some patients do report lasting pain reduction with repeated treatments over time (especially in neuropathic pain). [1]
However, without more high-quality, long-term trials, ketamine is not considered a first-line chronic pain therapy. It remains a second-line option for severe cases where the benefits outweigh the risks.
Risks and benefits of long-term ketamine therapy
Benefits
Maintenance ketamine infusions can reduce chronic pain levels and may decrease the need for opioids in some patients. [1] Patients who have exhausted other treatments might regain everyday function and quality of life with periodic ketamine therapy. Additionally, ketamine’s mood-elevating effects (due to its antidepressant properties) can be a positive side benefit for those who have chronic pain and coexisting depression or anxiety.
Risks
There are significant risks associated with long-term ketamine use. Ketamine’s well-known psychedelic side effects (hallucinations, dissociation, and anxiety) can occur at each infusion [1], and repeated exposures may lead to tolerance (noted as diminished impacts over time, prompting higher doses).
Abuse potential
Ketamine also has abuse potential. It can cause psychological dependence, and it is classified as a Schedule III controlled substance due to this risk. [1] Chronic high-dose use has been linked to severe organ damage, including bladder injury (ketamine-induced cystitis) and liver dysfunction. [1] Cognitive side effects (like memory issues) have also been observed with prolonged use. [1]
Because of these risks, doctors closely monitor patients on long-term ketamine, using the lowest effective dose and spacing infusions judiciously. The decision to continue maintenance therapy is always individualized, weighing improved pain control against potential harm.
Considerations for patients with a substance abuse history
Ketamine’s potential for abuse or misuse requires careful consideration in patients with a history of substance use disorder (SUD). While ketamine itself can be habit-forming, there is evidence suggesting it can be beneficial in treating certain addictions when used within a controlled therapeutic framework. Its effectiveness in managing addiction, however, heavily depends on strict oversight and careful administration. [12][13]
Evidence suggests that people who have a history of alcohol or drug misuse may have a higher risk of other substance abuse, including with ketamine. Because of the risk of harm from improperly used ketamine, it is often necessary to have closer monitoring parameters in some cases to promote patient safety. As a result, physicians often screen patients thoroughly for prior substance abuse before initiating ketamine therapy for pain. To promote patient safety, physicians may opt for closer monitoring, reduced dosages, or shorter durations of treatment within higher-risk use cases. [2]
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