A new pilot study published in Addiction Science & Clinical Practice presents promising results in the use of sub-dissociative doses of ketamine to assist patients transitioning to buprenorphine. The research, conducted by Lucinda A. Grande and colleagues, highlights ketamine's potential to reduce the withdrawal symptoms that frequently deter individuals with opioid use disorder (OUD) from initiating buprenorphine, particularly when they are dependent on fentanyl or methadone. The study's findings offer an innovative approach to one of the key challenges in OUD treatment, which is the management of buprenorphine-precipitated opioid withdrawal.
Buprenorphine has long been recognized as a life-saving medication for those with OUD, reducing overdose mortality by over 50%. However, many people who could benefit from buprenorphine are reluctant to start treatment due to fears of withdrawal symptoms. These can occur either spontaneously or, more severely, when buprenorphine displaces powerful opioids like fentanyl from the brain’s opioid receptors. The fear and experience of withdrawal symptoms—sometimes lasting up to a week—are especially intense in individuals with high-potency synthetic opioid dependence.
The pilot case series conducted over 14 months involved 37 patients, primarily those attempting to transition from illicit fentanyl or methadone use to buprenorphine. The patients received sublingual ketamine in low doses (16 mg), which is well below the threshold for inducing dissociative or anesthetic effects. The study results showed that 67% of the patients who tried ketamine successfully completed buprenorphine initiation, and 92% of those who completed the initiation were retained in treatment after 30 days.
Ketamine, primarily known as an anesthetic and increasingly used off-label for treatment-resistant depression and pain, has demonstrated an ability to reduce opioid tolerance and alleviate withdrawal symptoms through its action on NMDA-type glutamate receptors. In this study, ketamine's administration helped patients manage opioid withdrawal without entering a dissociative state, making it viable for outpatient treatment.
The study also offers a glimpse into the practical aspects of this new approach. Patients were prescribed up to eight doses of ketamine, which were either troches or sublingual syrup, compounded by local pharmacies. Patients used ketamine either prophylactically or to address emerging withdrawal symptoms during buprenorphine initiation. Over time, the researchers refined the treatment protocol, ultimately developing a four-day plan that minimized withdrawal for the final cohort of patients.
One of the key innovations in this study was delaying buprenorphine initiation and using ketamine to manage early withdrawal symptoms. By advising patients to abstain from fentanyl for 48–72 hours while using ketamine, the researchers observed that patients could begin buprenorphine with minimal discomfort. Clonazepam, a benzodiazepine, was also included in the protocol to prevent panic attacks, a common issue during buprenorphine initiation.
The results of this study are promising, particularly for populations dependent on potent synthetic opioids like fentanyl. Given that buprenorphine initiation is notoriously difficult for these patients, ketamine-assisted initiation could provide a crucial tool for increasing treatment uptake. The researchers caution that while ketamine can reduce the severity of withdrawal symptoms, further large-scale studies are necessary to confirm these findings and optimize the protocol.
The potential risks associated with ketamine, including cognitive effects and misuse, were also addressed in the study. Only two patients reported mild cognitive effects, and there were no instances of overdose or respiratory depression linked to ketamine use, even when patients returned to using fentanyl after incomplete treatment attempts.
The authors conclude that sub-dissociative doses of ketamine may offer a safer, more accessible method for initiating buprenorphine in outpatient settings, reducing barriers to a treatment that can significantly lower the risk of overdose. They call for further research to refine this approach and explore its applicability across various clinical settings.
The full study is accessible through the journal’s website at: Ketamine-assisted buprenorphine initiation: a pilot case series (clearnet).
If you're interested in such publications, please react and leave comments. This will be a sign for me to continue.