Ketamine for Chronic Pain? Evidence Still Missing

In a landscape where ketamine clinics are rapidly proliferating, evidence-based clinical decision-making matters even more.

A new recently published large review study by Ferraro et al. in the Cochrane database casts serious doubt on the effectiveness of ketamine for treating chronic non-cancer pain conditions such as fibromyalgia, nerve pain, and complex regional pain syndrome (CRPS).

About the Cochrane Review: 67 Randomized Controlled Trials and 2,300+ Patients

This review combined data from 67 randomized controlled trials involving more than 2,300 adult participants who had experienced chronic pain for at least three months. It analyzed various administration routes—intravenous (IV), oral, and topical ketamine—as well as other medications such as memantine, dextromethorphan, amantadine, and magnesium, that act on the same receptor as ketamine (the NMDA receptor).

The inclusion of other compounds that act on the NMDA-receptor beyond ketamine itself — such as memantine and dextromethorphan — strengthens the usefulness of this review. It examines the question—widely and in depth—of whether NMDA receptor antagonism as a class offers clinically usable analgesic benefit in chronic pain, rather than limiting the inquiry to ketamine alone. The answer, based on current evidence, appears to be: not reliably.

Clinical Results: No Clear Evidence Ketamine Reduces Chronic Pain at Any Time Point

Clinical results showed no clear evidence that ketamine reduces pain intensity over the short term (48 hours to one week), medium term (over one week to three months), or longer (three to six months) compared to placebo or standard care. The doses used for pain in the studies were comparable to the doses we use in the treatment of depression.

The overall quality of the evidence for efficacy was rated as "low to very low" due to small study sizes and methodological weaknesses. This means that it was difficult to draw firm conclusions about benefits or risks. Authors emphasized that while ketamine might have potential benefit, current data remain inconclusive.

A “low to very low” evidence quality rating in a Cochrane systematic review indicates that the true effect of the intervention may be substantially different from the estimated effect. For patients interested in ketamine as a pain treatment, this rating counsels caution rather than optimism.

Notably, none of the trials that were included in the review evaluated whether ketamine had effects on depressive symptoms or opioid usage—two areas where ketamine is sometimes proposed as beneficial. This omission further limits understanding of its broader impact in chronic pain populations

Point Loma Clinic’s Position: We Do Not Offer Ketamine for Chronic Pain

At our clinic, we do not administer ketamine for the treatment of chronic pain. We encourage individuals exploring ketamine for pain management to carry out their own online research, review credible scientific sources, and discuss the current state of evidence—including the limitations and uncertainties noted above—before considering care at any ketamine-based pain clinic.

Our ketamine treatment program is focused exclusively on evidence-supported psychiatric indications where the clinical evidence base is substantially stronger, primarily, but not excusively, depression and PTSD. If you have questions about whether ketamine therapy may be appropriate for a psychiatric condition, we invite you to schedule a consultation with our team.

Reference:

Ferraro MC et al:. Ketamine and other NMDA receptor antagonists for chronic pain. Cochrane Database of Systematic Reviews 2025, Issue 8.

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Alexander Papp, MD