Buprenorphine-Mediated Transition from Opioid Agonist to Antagonist Treatment: State of the Art and New Perspectives

Abstract

Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60–70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations.

Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: A very low dose naltrexone and buprenorphine open label trial

“…This conclusion is based on moderately high treatment retention, decrease in withdrawal scores, low proportion of adverse events, and high degree of patient satisfaction. If replicated in other clinical samples, a XR-NTX transfer rate of 60–70% with a 30-day proportion of 80% negative opioid urine tests would compare well against results of induction and early retention onto oral NTX (10%–40%), (Mannelli et al, 2012; Tucker et al, 2004), or buprenorphine and methadone (Kakko et al, 2007; Mannelli et al, 2012). …”

“…The range of doses was based on experience using it on inpatient units with patients tapering off methadone (Mannelli et al, 2003, 2009) or buprenorphine (Eissenberg et al, 1996; Johnson, 2001; Kosten et al, 1990; Umbricht et al, 1999). The BUP dose reduction schedule was based on available literature (Mannelli et al, 2012); dosing schedules are seen in Table 2.…”

Pharmacological strategies for detoxification

“…We should now ask how we can best tailor established treatments to suit the needs of individuals in difference circumstances . Questions remain regarding comparisons between treatments, combinations of treatments and optimal treatment regimens . Much attention has been given to approved treatments such as methadone tapering for opioid dependence and benzodiazepines for alcohol dependence, and more research is required into emerging treatment possibilities, such as oxytocin and flumazenil .…”

Management of opioid use disorders: a national clinical practice guideline

“…A stepped care strategy involving initial treatment with buprenorphine-naloxone and transition to methadone if necessary was shown to be equally efficacious as an optimally delivered methadone treatment. 56 In contrast, although transitioning to buprenorphine-naloxone from methadone is achievable, 57 this practice must be individually tailored and can be highly challenging for some patients. 58 Indeed, when transitioning from higher daily doses of methadone, there is an increased risk of substantial withdrawal symptoms and consequent relapse; adjunct medications or inpatient treatment (e.g., medically supervised withdrawal management programs) may be required for safe conversion in such cases.…”