Spravato (Esketamine) is Not Recommended for Chronic Pain Management
Spravato (esketamine) is not recommended for the treatment of chronic pain as it lacks FDA approval for this indication and has insufficient evidence supporting its use for pain management.
Current Status of Esketamine for Pain
Esketamine (Spravato) is currently only FDA-approved for treatment-resistant depression and depressive symptoms in adults with major depressive disorder with suicidal ideation or behavior 1. Despite its pharmacological relationship to ketamine, which has been studied for pain management, Spravato has not been established as an effective treatment for chronic pain conditions.
Evidence Gap for Pain Management
The available clinical guidelines do not support the use of esketamine for chronic pain:
- No major pain management guidelines recommend esketamine for chronic pain treatment 1
- Current evidence focuses primarily on esketamine's psychiatric applications rather than analgesic properties
- Research on esketamine for pain remains largely experimental and preliminary 2, 3
Recommended First-Line Treatments for Chronic Pain
Instead of esketamine, the following evidence-based treatments should be considered for chronic pain management:
For Neuropathic Pain:
- First-line: Gabapentin or pregabalin 1, 4
- Second-line: Tricyclic antidepressants (e.g., amitriptyline) or SNRIs (e.g., duloxetine) 4
- Third-line only: Opioids should not be used as first-line agents for chronic neuropathic pain due to risks of pronociception, cognitive impairment, respiratory depression, endocrine changes, and potential for misuse 1
For Musculoskeletal Pain:
- First-line: Acetaminophen and NSAIDs 1
- Acetaminophen has fewer side effects than NSAIDs but is slightly less effective
- NSAIDs provide better pain relief but carry gastrointestinal and cardiovascular risks
- Second/Third-line: Tramadol may be considered for osteoarthritis (dosing range 37.5-400 mg daily) for up to 3 months 1
Potential Future Role of Esketamine in Pain Management
While current evidence does not support routine use, several ongoing clinical trials are investigating esketamine for specific pain conditions:
- A phase II trial is examining intranasal esketamine for chronic opioid-refractory cancer pain 2
- Research is exploring novel delivery systems like sustained-release esketamine for neuropathic pain 3
- Studies are comparing intermittent versus continuous esketamine infusions for complex regional pain syndrome 5
Important Considerations and Risks
If esketamine were to be used off-label for pain (which is not recommended), clinicians should be aware of:
- Common side effects: dissociation, nausea, headache, elevated heart rate and blood pressure 6
- Risk of lower urinary tract symptoms with long-term use 6
- Potential for cognitive effects, though clinical trials for depression showed stable or improved cognition over time 6
- Need for specialized administration and monitoring protocols similar to those required for its psychiatric indications
Conclusion
For chronic pain management, clinicians should follow established guidelines that recommend non-opioid analgesics, anticonvulsants, and certain antidepressants as first-line treatments 1, 4. Opioids should be reserved for cases where other treatments have failed and should be prescribed judiciously with careful monitoring 1. Esketamine (Spravato) should not be used for chronic pain management outside of clinical trials until sufficient evidence supports its safety and efficacy for this indication.