Is DMSO (Dimethyl Sulfoxide) safe to mix with topical ketamine?

Safety of Mixing DMSO with Topical Ketamine

DMSO can be safely mixed with topical ketamine and may actually enhance its effectiveness through increased skin penetration, though caution should be exercised regarding potential skin reactions.

Mechanism and Rationale

DMSO (Dimethyl Sulfoxide) is a common solvent with several properties that make it suitable for combination with topical ketamine:

• DMSO has free-radical scavenging properties and penetrates tissue when applied topically 1
• DMSO enhances diffusion of other chemicals through the skin, making it an effective penetration enhancer 2
• Ketamine works primarily as an N-methyl-D-aspartate (NMDA) receptor antagonist in peripheral terminals of primary nociceptive afferents 3

Evidence for Safety and Efficacy

The combination of DMSO with topical ketamine is supported by clinical evidence:

• Topical ketamine is typically compounded at concentrations of 0.5% to 20%, either alone or in combination with other analgesics 4
• The American College of Physicians recommends starting with 0.5% ketamine compounded with 1-2% amitriptyline for chronic pain management 3
• DMSO has been used safely as a vehicle for various drugs, including topical applications 2
• Despite using high concentrations of topical ketamine, clinically significant side effects are rare 4

Potential Concerns and Precautions

When using DMSO with topical ketamine, be aware of:

1. Skin reactions: DMSO can cause local erythema, skin rash, and pruritus, especially at higher concentrations 1, 5
2. Penetration enhancement: DMSO will increase absorption of ketamine through the skin, which may require dosage adjustments 2
3. Contraindications: Avoid application on open wounds or broken skin 3
4. Drug interactions: The safety of DMSO in combination with other drugs has not been fully established; neurotoxic interactions have been reported with some medications 2

Recommended Approach

When mixing DMSO with topical ketamine:

• Start with lower concentrations of DMSO (around 50%) to minimize skin irritation 1
• Apply to intact skin only
• Monitor for local skin reactions, especially during initial applications
• Document baseline pain scores and reassess regularly using validated pain scales 3
• Consider a test application on a small area before widespread use

Monitoring and Follow-up

• Assess pain relief, functional improvement, and adverse effects at 2-4 weeks
• If no improvement after 4-6 weeks of optimized therapy, consider alternative treatments 3
• Discontinue if significant skin irritation occurs

The combination of DMSO and topical ketamine represents a potentially effective approach for managing chronic pain conditions, particularly neuropathic pain, with DMSO enhancing the penetration and potentially the efficacy of ketamine while maintaining a favorable safety profile when used appropriately.