Ketamine Therapy for Chronic Pain

Ketamine for chronic pain is a different clinical world from ketamine for psychiatric indications. The strongest evidence sits in CRPS (complex regional pain syndrome) — refractory neuropathic pain follows; fibromyalgia, cancer pain, and phantom limb pain are weaker indications. Pain-medicine ketamine is anesthesiology-led, uses longer infusions (often multi-hour or multi-day), and runs in CPSA/CPSO/CPSBC-accredited non-hospital surgical or medical/surgical facilities. This article is for patients with refractory chronic pain who are researching ketamine, and it is honest about ATMA CENA's role: ATMA CENA is a psychiatric/mental-health clinic, not a primary pain clinic. For CRPS or refractory neuropathic pain, the right care pathway is a pain-medicine physician at an accredited facility. Where chronic pain is comorbid with treatment-resistant depression, PTSD, or anxiety — which it very often is — ATMA CENA's coordinated care model provides the mental-health side of integrated care alongside your pain specialist.

Key takeaways

• Ketamine for chronic pain is off-label. Health Canada has approved ketamine as an anaesthetic; pain-medicine use is off-label and standard practice.
• CRPS has the strongest evidence (Sigtermans 2009, Schwartzman 2009, Goldberg 2005). Refractory neuropathic pain has weaker evidence; fibromyalgia is weaker still.
• The ASRA 2018 consensus guidelines (Cohen et al.) are the multi-society standard for IV ketamine in chronic pain — bolus up to 0.35 mg/kg, infusion 0.5–2 mg/kg/hr, minimum 80 mg over >2 hours.
• Workers' compensation pathways for ketamine in chronic pain: WSIB (Ontario's Workplace Safety and Insurance Board) lists ketamine on Musculoskeletal, Chronic Pain Disability, and CNS/PNS formularies; WCB Alberta covers ketamine for compensable CRPS and refractory neuropathic pain; WorkSafeBC reviews case-by-case.
• VAC covers ketamine drug forms (IV, oral, intranasal, compounded cream) for service-related chronic pain on a case-by-case basis.
• ATMA CENA's role: psychiatric/mental-health KAP. For pain-primary care, the pathway is referral to a pain-medicine specialist; ATMA CENA supports comorbid mental health alongside pain treatment via coordinated care.

What is ketamine for chronic pain — and how does it differ from psychiatric ketamine?

Ketamine for pain and ketamine for depression share the same molecule but differ substantially in protocol:

The mechanistic story behind ketamine's analgesic effect is NMDA antagonism, with downstream effects on central sensitization (the wind-up phenomenon underlying chronic neuropathic pain) and possibly opioid-receptor interactions. The mechanism overlaps with the antidepressant effect but is not identical — and the dosing, duration, and clinical setting differ accordingly.

What the evidence actually shows — by indication

CRPS (Complex Regional Pain Syndrome) — strongest evidence

CRPS Type 1 has the strongest pain-medicine ketamine evidence base.

Sigtermans et al. 2009 — Pain — RCT in 60 patients with CRPS-1 receiving 4-day continuous IV ketamine infusion or placebo. Significant pain relief in the ketamine arm sustained for up to 11 weeks. Pivotal evidence (PubMed).

Schwartzman et al. 2009 — Pain — outpatient double-blind placebo-controlled study of low-dose IV ketamine in CRPS. Significant pain reduction with 10-day outpatient infusion course (PubMed).

Goldberg et al. 2005 — Pain Medicine — multi-day low-dose ketamine infusion case series for refractory CRPS. Established the multi-day protocol (PubMed).

The honest summary for CRPS: roughly half of CRPS patients respond meaningfully to a multi-day ketamine course, with effects lasting weeks to months. CRPS is the indication where pain-medicine ketamine is most evidence-supported.

Refractory neuropathic pain — weaker evidence

Mixed neuropathic pain (post-herpetic neuralgia, diabetic neuropathy, post-surgical neuropathic pain, central pain syndromes) shows variable response to ketamine in RCTs and case series. Effect sizes are smaller than CRPS, and durability is typically days to a few weeks.

Niesters, Martini, Dahan 2014 — British Journal of Clinical Pharmacology — foundational systematic review of ketamine for chronic pain. Concluded that ketamine has a clear mechanistic rationale and observable analgesic effect in several chronic pain conditions, but emphasized risks of long-term use including hepatotoxicity and urinary tract complications (PubMed).

Phantom limb pain

Best evidence is for perioperative use (IV or epidural) to prevent or reduce phantom limb pain after amputation. Established stump and phantom pain shows variable response to ketamine; oral ketamine is an emerging option for some patients. Long-term data limited.

Spinal cord injury pain

Multi-day low-dose infusion studies (often as adjuvant to gabapentin) report short-term efficacy that ceases approximately 2 weeks post-infusion. Less robust than CRPS evidence.

Fibromyalgia — weak

Ketamine infusion for fibromyalgia has been studied in small trials. Single-dose responses are typically short-lived. Multi-day or repeated regimens show partial response in ~40% of patients, partial in ~15%, no response in ~45%. Larger RCTs are needed; current Canadian and U.S. guidelines do not consider ketamine first-line for fibromyalgia.

Cancer pain — palliative-specific

Cochrane reviews have reported insufficient evidence to recommend ketamine as a routine adjuvant to opioids in cancer pain. In practice, ketamine is sometimes used in palliative or in-hospital settings for refractory cancer pain unresponsive to opioids, often for short periods.

ASRA 2018 consensus guidelines — the multi-society standard

The American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists co-published the Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain (Cohen et al., Reg Anesth Pain Med 2018) — the most-cited multi-society guidance for pain-medicine ketamine. Key parameters:

• Bolus dose: up to 0.35 mg/kg
• Infusion rate: 0.5–2 mg/kg/hr
• Minimum total: 80 mg over more than 2 hours
• Indications with evidence: CRPS (moderate evidence), phantom limb pain, mixed neuropathic pain (weaker evidence)
• Follow-up therapy: oral ketamine (~150 mg/day) or dextromethorphan; intranasal for breakthrough pain in selected patients

A companion document covers acute pain (Schwenk et al., 2018). Most Canadian pain-medicine clinics align with ASRA 2018 protocols.

Canadian regulatory framework

Federal — Health Canada. Ketamine is a Schedule I controlled substance, prescribed off-label for chronic pain. Spravato is approved only for treatment-resistant depression and is not a pain indication.

Provincial — accreditation requirements. IV ketamine in non-hospital settings requires facility-level accreditation in most provinces:

• Alberta — CPSA: Non-Hospital Surgical Facility (NHSF) accreditation under Off-label IV Sedative/Anaesthetic Standards. CPSA's Ketamine Clinical Toolkit and March 2026 Ketamine Prescribing Guidance apply.
• Ontario — CPSO: Out-of-Hospital Premises Inspection Program (OHPIP) Level II for IV ketamine; deep-sedation credentialing required.
• British Columbia — CPSBC: Non-Hospital Medical and Surgical Facilities Accreditation Program (NHMSFAP); see NHMSFAP standards for ketamine and lidocaine infusions for chronic pain.
• Saskatchewan — CPSS: Non-Hospital Treatment Facility (NHTF) accreditation required for IV/IM/SQ ketamine (more restrictive than AB).
• Quebec — CMQ, Manitoba — CPSM, Atlantic provinces — varied frameworks; pain-medicine clinics are typically accreditation-bound under analogous programs.

Oral, intranasal, IM, and sublingual ketamine generally have lighter facility requirements than IV across most provinces.

Workers' compensation and insurance

Workers' compensation is the most important coverage pathway for chronic pain ketamine in Canada.

WSIB Ontario. Ketamine and esketamine are listed on multiple specialty formularies (Musculoskeletal, CNS/PNS, Chronic Pain Disability, Psychotraumatic, Serious Injury) with prior authorization for compensable injuries. Coverage criteria typically include failure of ≥3 first/second-line neuropathic pain medications at maximum tolerated doses, multidisciplinary pain team assessment, and qualified specialist administration. Oral ketamine is restricted to short-term step-down (typically max 6 months). See WSIB ketamine and esketamine formulary decision.

WCB Alberta. Covers ketamine for compensable CRPS and refractory neuropathic pain on a case-by-case basis under the Pharmaceutical Ketamine and Esketamine procedure.

WorkSafeBC. Case-by-case evaluation. WorkSafeBC's Evidence-Based Practice Group has published reviews on IV and oral ketamine for chronic non-cancer pain; the position is cautious, citing concerns about evidence quality and bias.

WCB Manitoba, WCB Saskatchewan, WCB Nova Scotia, CNESST Quebec. Reviewed case-by-case without formal listings equivalent to WSIB Ontario.

Veterans Affairs Canada. Covers ketamine drug forms (IV, oral, intranasal, compounded cream) for service-related chronic pain on a case-by-case basis. The VAC Chronic Pain Centre of Excellence coordinates pain care for service-connected veterans.

Private insurance. Generic IV/IM/SL ketamine for chronic pain is generally not covered by private extended-health plans. Some plans cover compounded preparations with prior authorization.

For full insurance navigation, see Insurance Coverage for Ketamine Therapy.

Where ATMA CENA fits in chronic pain care

ATMA CENA is a psychiatric/mental-health clinic. ATMA CENA is not a primary pain clinic. Pain-medicine ketamine is anesthesiology-led, uses longer infusions, and requires pain-medicine specialist credentialing.

That said, chronic pain and psychiatric comorbidity overlap heavily:

• Comorbid TRD with chronic pain. A meaningful fraction of chronic pain patients meet criteria for treatment-resistant depression. ATMA CENA can address the depression component while a pain-medicine clinic handles the pain ketamine course.
• Comorbid PTSD with chronic pain. Service-related chronic pain in veterans frequently co-occurs with PTSD. ATMA CENA's coordinated care model can support the mental-health side.
• Anxiety + chronic pain. Generalized anxiety, panic, and pain-anticipation anxiety are common; ATMA CENA's KAP (ketamine-assisted psychotherapy) model addresses these.

The honest framing: for primary CRPS or refractory neuropathic pain, see a pain-medicine specialist at an accredited facility. ATMA CENA can support the comorbid psychiatric layer through coordinated care or referral to a member clinic, in coordination with the pain physician.

Safety and monitoring

Ketamine for chronic pain has specific safety considerations beyond psychiatric use:

• Hepatotoxicity. Repeated multi-day or chronic ketamine courses have been associated with drug-induced liver injury (Noppers et al., 2010). Baseline and ongoing liver-function tests are standard.
• Urinary tract effects. Chronic ketamine use, particularly higher cumulative dosing, has been linked to ketamine-induced cystitis. Most reports are from recreational misuse, but clinical caution applies for repeated courses.
• Tolerance and dependence. Therapeutic supervised use has not been associated with clinically problematic dependence in published trials, but ketamine itself has misuse potential — relevant for the addiction screening discussion in any pain population on chronic opioids.
• Cardiovascular. Transient hypertension and tachycardia during infusion are common; baseline cardiovascular screening is standard.
• Dissociation. Anesthesiology-led pain protocols often produce more pronounced dissociation than 40-minute psychiatric infusions; monitoring is part of the standard model.

Frequently asked questions

Is ketamine approved for chronic pain in Canada? No. Ketamine is approved by Health Canada as an anaesthetic; pain-medicine use is off-label and standard practice. Spravato is approved only for treatment-resistant depression and is not a pain indication.

What chronic pain conditions does ketamine help most? The strongest evidence is for CRPS, followed by refractory neuropathic pain. Phantom limb pain (perioperative use), spinal cord injury pain, and fibromyalgia have weaker evidence. Cancer pain is sometimes used in palliative settings.

How is pain-medicine ketamine different from psychiatric ketamine? Setting (anesthesiology-led pain clinic vs psychiatric/KAP clinic), protocol (often multi-hour or multi-day infusions vs 40-minute psychiatric infusion), and integration (no psychotherapy wraparound in pain-medicine vs preparation + integration in KAP). Same molecule; very different clinical model.

Does WSIB cover ketamine for chronic pain in Ontario? Yes — WSIB Ontario lists ketamine and esketamine on Musculoskeletal, CNS/PNS, Chronic Pain Disability, Psychotraumatic, and Serious Injury formularies with prior authorization for compensable injuries. Coverage typically requires failure of multiple first/second-line neuropathic pain medications and qualified specialist administration.

Does WCB Alberta cover ketamine for chronic pain? Yes — WCB Alberta covers ketamine for compensable CRPS and refractory neuropathic pain on a case-by-case basis under the Pharmaceutical Ketamine and Esketamine procedure.

Does VAC cover ketamine for service-related chronic pain? Yes — VAC covers ketamine drug forms (IV, oral, intranasal, compounded cream) for service-related chronic pain on a case-by-case basis. Coordinates with the VAC Chronic Pain Centre of Excellence.

Where do I go for ketamine for CRPS in Canada? Pain-medicine specialists at CPSA/CPSO/CPSBC-accredited non-hospital surgical or medical/surgical facilities. The ATMA CENA information call can help orient you to provincial pain-medicine pathways.

Can ATMA CENA help me if I have chronic pain plus depression or PTSD? Yes — through the coordinated care model. Your pain-medicine specialist remains the primary pain provider; ATMA CENA's network supports the mental-health side via KAP for comorbid TRD, PTSD, or anxiety. Information call walks through how this works.

Are there long-term safety concerns? Yes. Hepatotoxicity (Noppers 2010 case series), urinary tract effects with chronic high-dose use, and cardiovascular effects during infusion. Pain-medicine clinics monitor liver function, urinary symptoms, and blood pressure. Therapeutic supervised use has been generally well tolerated.

What about opioid-sparing in chronic pain? Ketamine has opioid-sparing potential in the perioperative setting and in some chronic pain protocols. The ASRA acute pain consensus document (Schwenk 2018) covers this domain. Discuss with your pain-medicine physician.

Where can I learn about ketamine for psychiatric indications instead? See Ketamine Therapy for Depression, Ketamine Therapy for Treatment-Resistant Depression (deep dive), Ketamine Therapy for PTSD, Ketamine Therapy for Anxiety, and Ketamine Therapy for Bipolar Depression.

Sources

1. ATMA CENA — coordinated care: https://psychedelic.healthcare/find-care
2. Cohen SP, et al. (2018). Consensus 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. Reg Anesth Pain Med. https://pubmed.ncbi.nlm.nih.gov/29870458/
3. Schwenk ES, et al. (2018). Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management. Reg Anesth Pain Med. https://pubmed.ncbi.nlm.nih.gov/29870456/
4. Niesters M, Martini C, Dahan A (2014). Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. https://pubmed.ncbi.nlm.nih.gov/23834205/
5. Sigtermans MJ, et al. (2009). Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain. https://pubmed.ncbi.nlm.nih.gov/19783099/
6. Schwartzman RJ, et al. (2009). Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. https://pubmed.ncbi.nlm.nih.gov/19783099/
7. Goldberg ME, et al. (2005). Multiday low-dose ketamine infusion for complex regional pain syndrome. Pain Med. https://pubmed.ncbi.nlm.nih.gov/15773879/
8. Noppers IM, et al. (2010). Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain. Pain. https://pubmed.ncbi.nlm.nih.gov/20705391/
9. CPSA — Ketamine Clinical Toolkit: https://cpsa.ca/resources/ketamine-toolkit/
10. CPSBC — NHMSFAP Ketamine and Lidocaine Infusions for Chronic Pain: https://www.cpsbc.ca/files/pdf/NHMSFAP-AS-Ketamine-Lidocaine-Infusions-for-Treatment-of-Chronic-Pain.pdf
11. WSIB Ontario — Ketamine and Esketamine Formulary Decision: https://www.wsib.ca/en/drug-formulary-listing-decision-ketamine-and-esketamine
12. WCB Alberta — Pharmaceutical Ketamine and Esketamine Procedure: https://www.wcb.ab.ca/about-wcb/procedures-manual/pharmaceutical-ketamine-and-esketamine.html
13. Veterans Affairs Canada — Chronic Pain Centre of Excellence: https://www.veterans.gc.ca/en/mental-and-physical-health/physical-health-and-wellness/chronic-pain-centre-excellence-canadian-veterans

Related articles in this cluster

• Ketamine Therapy in Canada
• What Is Ketamine Therapy?
• Ketamine Therapy Cost in Canada
• How to Qualify for Ketamine Therapy in Canada
• Ketamine Therapy for Depression
• Ketamine Therapy for PTSD
• Ketamine Therapy for Anxiety
• Insurance Coverage for Ketamine Therapy
• Find care near you

Last updated: 2026-05-06