What are the considerations for using ketamine in a patient with a history of opioid addiction or dependence who is currently taking Suboxone (buprenorphine and naloxone)?

Ketamine Use in Patients on Suboxone (Buprenorphine/Naloxone)

Ketamine can be safely used in patients taking Suboxone and represents a valuable opioid-sparing analgesic option, particularly for acute pain management in this population with opioid tolerance. 1

Pharmacologic Rationale

Ketamine functions as an NMDA receptor antagonist with a distinct mechanism from opioid receptors, making it pharmacologically compatible with buprenorphine therapy 1. The two medications work through different pathways:

• Ketamine blocks NMDA/glutamate receptors and provides analgesia independent of mu-opioid receptor activity 1
• Buprenorphine occupies mu-opioid receptors as a partial agonist with high binding affinity 2, 3
• No direct pharmacologic interaction exists between these mechanisms, allowing concurrent use 1

Clinical Applications

For Acute Pain Management

Continue the patient's usual Suboxone dose and add ketamine as an adjunctive analgesic when acute pain requires treatment beyond what buprenorphine provides. 2

• Sub-anesthetic ketamine doses (boluses <0.35 mg/kg or infusions at 0.5-1 mg/kg/h) effectively reduce pain scores and opioid requirements without requiring intensive monitoring 1
• Ketamine is particularly valuable for patients with opioid tolerance who have suboptimal response to standard opioid therapy 4
• The maintenance buprenorphine dose does NOT provide adequate analgesia for acute pain—this is a critical misconception 1

For Patients with History of Opioid Addiction

Ketamine serves as an ideal alternative analgesic for patients with opioid use disorder who require pain control but should avoid additional full opioid agonists. 5

• Low-dose ketamine (≤0.5 mg/kg) demonstrates equivalent or superior efficacy compared to opioids for acute pain in emergency settings 5
• Ketamine's opioid-sparing effects minimize exposure to potentially triggering substances in patients maintaining recovery 1, 4
• The theoretical concern about relapse from opioid analgesics is often exaggerated—unrelieved pain itself serves as a more significant relapse trigger 1

Emerging Application: Precipitated Withdrawal

Ketamine infusions show promise for treating buprenorphine-precipitated opioid withdrawal (BPOW), though this remains an evolving area. 6, 7

• Case reports demonstrate ketamine infusions resolving severe precipitated withdrawal when buprenorphine is initiated too early 6
• Sublingual ketamine 16 mg at sub-dissociative doses assisted outpatient buprenorphine initiation in 67% of patients who tried it, with most reporting reduction or elimination of withdrawal symptoms 7
• This application requires further research but represents a potential solution to a significant clinical barrier 6, 7

Dosing Protocols

For Analgesia in ICU/Hospital Settings

• Bolus dosing: <0.35 mg/kg IV 1
• Continuous infusion: 0.5-1 mg/kg/h (maximum 1 mg/kg) 1
• IV-PCA addition: 1-5 mg per dose 1
• Administer as adjunct to continued buprenorphine maintenance therapy 1

For Emergency Department Acute Pain

• Low-dose ketamine: ≤0.5 mg/kg IV or equivalent 5
• Provides pain relief within 15-30 minutes with peak effect at 30 minutes 5

For Outpatient Buprenorphine Initiation (Experimental)

• Sublingual ketamine: 16 mg per dose, 4-8 doses total 7
• This represents 3-6% of an anesthetic dose and remains sub-dissociative 7

Safety Considerations

Adverse Effects to Monitor

Psychotomimetic side effects (dysphoria, nightmares, hallucinations) occur with ketamine, particularly at higher doses, but are generally manageable. 1

• Neurological side effects show a pooled risk ratio of 1.41 compared to opioids 5
• Psychological side effects have a pooled risk ratio of 2.83 5
• Two patients in one series experienced cognitive changes when doses exceeded the effective range 7
• Gastrointestinal and cardiopulmonary side effects are less common than with opioids 5

Contraindications

Do not use ketamine in patients with uncontrolled cardiovascular disease, pregnancy, active psychosis, severe liver dysfunction, high intracranial pressure, or elevated ocular pressure. 1

Monitoring Requirements

• Sub-anesthetic doses do not require intensive monitoring 1
• Monitor sedation levels and respiratory status as with any analgesic 1
• Watch for emergence of psychotomimetic symptoms, particularly with higher doses 1

Critical Clinical Pitfalls

The most dangerous misconception is that maintenance buprenorphine provides adequate analgesia for acute pain—it does not. 1

• Buprenorphine's high receptor binding affinity may actually block effects of additional opioids at lower doses 2
• Patients on Suboxone often have lower pain tolerance due to "pain facilitation syndrome" from their addiction history 1
• Fears of respiratory depression from combining ketamine with buprenorphine are theoretical and not clinically demonstrated 1

Never withhold appropriate analgesia due to concerns about addiction relapse—untreated pain poses greater relapse risk than adequate pain control. 1

• Acute pain decreases the euphorogenic qualities of opioids 1
• The stress of unrelieved pain serves as a substantial trigger for drug use 1
• Patients receiving adequate pain relief are less likely to exhibit drug-seeking behaviors 1

Practical Algorithm

1. Continue the patient's usual Suboxone dose unchanged 2
2. Add ketamine at sub-anesthetic doses for acute pain (bolus <0.35 mg/kg or infusion 0.5-1 mg/kg/h) 1
3. Consider dividing buprenorphine into more frequent doses (every 6-8 hours) if chronic pain management is needed 2
4. Add short-acting opioid analgesics if ketamine alone is insufficient, recognizing that higher doses may be needed due to buprenorphine's receptor occupancy 2
5. Monitor for psychotomimetic effects and adjust ketamine dose downward if they occur 1, 7