Supplementary Material for: Low-dose buprenorphine initiation for opioid agonist therapy in patients with opioid use disorder; a Dutch consensus paper

Introduction:
Buprenorphine, a partial opioid agonist, is widely used as treatment of opioid use disorder. Traditionally, the original opioids are abruptly stopped, whereafter the buprenorphine is titrated over the course of several days. An alternative approach is low-dose buprenorphine initiation (LDBI), where buprenorphine is titrated more gradually, while the original opioids are still being used. Literature suggest LDBI may be associated with less withdrawal symptoms, though no standardized protocol for LDBI currently exists. This study aimed to establish consensus on the application of LDBI in Dutch clinical practice.

Methods:
A Delphi method was employed, involving a systematic literature review to develop statements on the application of LDBI. Experts reviewed these statements across three rounds, achieving consensus at a 75% agreement threshold.

Results:
Thirteen physicians with demonstrated expertise in LDBI participated, with nine completing all three rounds. Over three consultation rounds, consensus was achieved on 28 statements about indications for LDBI and dosing regimens, though variation in titration procedures was observed. The panel agreed that the starting dose can range between 10-20micrograms/hour for transdermal patches and 0.2-1.0mg for sublingual tablets; dose can be increased daily with a maximum of 100% of the previous daily dose. Further, the original opioids should not be discontinued before day seven after LDBI.

Conclusion:
Though various protocols for LDBI exist, physicians experienced with LDBI agreed on the range of safe LDBI regimens. Further research is necessary to develop comprehensive guidelines for LDBI in patients with opioid use disorder.