Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use.
Christian Hailozian, Joshua Luftig, Amy Liang, Melena Outhay, Monish Ullal, Erik S Anderson, Mariah Kalmin, Steve Shoptaw, Mark K Greenwald, Andrew A Herring
Journal of Addiction Medicine November 16, 2021 DOI: 10.1097/adm.0000000000000929 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case study Case report Peer reviewed |
|---|---|
| Sample size | 1 |
| Population | A patient with opioid use disorder using illicit fentanyl who experienced severe buprenorphine-precipitated opioid withdrawal during outpatient low-dose buprenorphine induction |
| Interventions | Ketamine Buprenorphine Extended-release subcutaneous buprenorphine |
| Dose | ketamine 0.6 mg/kg intravenous over 1 hour; buprenorphine 16 mg sublingual single dose; extended-release subcutaneous buprenorphine 300 mg monthly |
| Duration | 90-day follow-up |
| Topics | Esketamine Ketamine |
| Key findings | The authors report that severe buprenorphine-precipitated opioid withdrawal was successfully treated in the emergency department with intravenous ketamine (0.6 mg/kg over 1 hour) combined with a single 16 mg sublingual buprenorphine dose, followed by monthly extended-release subcutaneous buprenorphine (300 mg); at 90 days the patient remained in treatment and reported continuous fentanyl abstinence. They propose ketamine may have a therapeutic role in BPOW and call for prospective comparative studies. |
Abstract
Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine's partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described. We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use. This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.
Comparable studies
Other case reports and case series on ketamine, most cited first.
Citations in the library
Cited by 11
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders. Biological Psychiatry March 15, 2025
- Ketamine in treating opioid use disorder and opioid withdrawal: a scoping review. Frontiers in Psychiatry 2025
- The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Drug and Alcohol Dependence December 1, 2023
- Ketamine-assisted buprenorphine initiation: a pilot case series. Addiction Science & Clinical Practice August 29, 2024
and 6 more in the library