The effects of buprenorphine depot implants on patient sleep and quality of life: findings from a mixed-methods pilot trial

Abstract

Background: Opioid use disorder is a critical public health concern and the negative effects of opioids on sleep may reinforce addiction. The objective of this pilot study was to incorporate objective and subjective measures to examine if implantable buprenorphine altered patient sleep and quality of life after crossover from daily-dosed sublingual buprenorphine (clinicaltrials.gov ID: NCT02896660).

Methods: This pilot study utilized patient self-report and actigraphy to measure the effects of buprenorphine on sleep and quality of life. Patients (n = 15) on sublingual buprenorphine treatment continuously wore an actigraphy device on their wrist for 90 days. Patients’ sleep was monitored for 30 days, after which patients were crossed over to implantable buprenorphine and monitored for 60 days. Patients completed self-assessments at baseline, days 30, 60, and 90. Five randomized patients completed a short qualitative interview at day 90.

Results: In actigraphy measures, patient sleep and energy level remained constant following crossover to BI. Both before and after crossover patients perceived their sleep to be worse than that measured by actigraphy; however, quality of life improvements were reported, despite no changes in energy level or sleep efficiency.

Conclusions: This is the first time clinically stable buprenorphine patients’ sleep has been evaluated with actigraphy in combination with self-report. Self-report data added valuable context to actigraphy findings. Stabilized dose delivery via implant allowed patients to re-frame their recovery experience, creating positive impacts on psychosocial health and quality of life despite no objective difference in sleep.

Keywords:

• Opioid-use disorder
• buprenorphine
• actigraphy
• patient-reported outcomes
• sleep

Acknowledgements

The authors acknowledge Elizabeth McDevitt, HITLAB, for performing actigraphy analysis; Christina Morgan, Frost Medical, for her support in data collection; Rachel Adams, HITLAB, for data management support; Laura Pugliese, HITLAB, for manuscript support.

Ethics statement

The authors confirm that this manuscript adheres to the ethical guidelines of Addiction Research & Theory. Any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies and such approvals are acknowledged within the manuscript. All patients were able to understand spoken or written English and provided written informed and verbal consent. This study was conducted in accordance with the ethical principles in the Declaration of Helsinki, consistent with Good Clinical Practice and conducted in accordance with the regulations of the US FDA as described in 21 Code of Federal Regulations 50 and 56, applicable laws. Institutional Review Board approval was obtained from the Chesapeake IRB (Pro00018757) and registered on clinicaltrials.gov (ID: NCT02896660). The authors also confirm that all mandatory laboratory health and safety procedures have been complied with in the course of conducting the experimental work reported in the paper. The authors confirm that all patients described in this paper have given written consent to the inclusion of material pertaining to themselves and have acknowledged that they cannot be identified via the paper; the authors confirm that they have anonymized the subjects of this trial.

Disclosure statement

Michael Frost discloses that he has previously received research and consulting fees from Braeburn Pharmaceuticals. For the remaining authors none were declared. Since the completion of this study, Titan Pharmaceuticals, Inc. now holds the rights to Probuphine.

Additional information

Funding

Funding for this study was provided to HITLAB by Braeburn Pharmaceuticals. Braeburn supplied the buprenorphine implants and advised on the study design and methods for implementation but were not involved in the implementation of the research or evaluation of study results, which were performed independently by HITLAB. Braeburn personnel were involved in the initial quality control review of the manuscript. Michael Frost discloses that he has previously received research and consulting fees from Braeburn Pharmaceuticals. For the remaining authors none were declared.

Notes on contributors

Kathleen Lynch

Kathleen Lynch, MS is a medical anthropologist with expertise in qualitative research methodologies. Ms. Lynch served as the study coordinator and lead data analyst on this study. Michael P. Frost, MD, FACP, FASAM, is a board-certified addiction medicine physician as well as President, Medical Director, Medical Expert, and Principal Investigator of Frost Medical in Conshohocken, Pennsylvania, where he treats patients with various substance addictions using a holistic approach. Dr. Frost served as site director for this study. Sara Chokshi, DrPH is an applied public health social scientist with expertise in health information technology and user-centered design. Dr. Chokshi served as the project manager for this study. Stan Kachnowski, PhD, MPA, CSEP, is the Chair of Healthcare Innovation Technology Lab and has conducted extensive research focused on the efficacy and diffusion of digital health technologies. Dr. Kachnowski served as the Principal Investigator of this study.

M. Frost

Kathleen Lynch, MS is a medical anthropologist with expertise in qualitative research methodologies. Ms. Lynch served as the study coordinator and lead data analyst on this study. Michael P. Frost, MD, FACP, FASAM, is a board-certified addiction medicine physician as well as President, Medical Director, Medical Expert, and Principal Investigator of Frost Medical in Conshohocken, Pennsylvania, where he treats patients with various substance addictions using a holistic approach. Dr. Frost served as site director for this study. Sara Chokshi, DrPH is an applied public health social scientist with expertise in health information technology and user-centered design. Dr. Chokshi served as the project manager for this study. Stan Kachnowski, PhD, MPA, CSEP, is the Chair of Healthcare Innovation Technology Lab and has conducted extensive research focused on the efficacy and diffusion of digital health technologies. Dr. Kachnowski served as the Principal Investigator of this study.

S. Chokshi

Kathleen Lynch, MS is a medical anthropologist with expertise in qualitative research methodologies. Ms. Lynch served as the study coordinator and lead data analyst on this study. Michael P. Frost, MD, FACP, FASAM, is a board-certified addiction medicine physician as well as President, Medical Director, Medical Expert, and Principal Investigator of Frost Medical in Conshohocken, Pennsylvania, where he treats patients with various substance addictions using a holistic approach. Dr. Frost served as site director for this study. Sara Chokshi, DrPH is an applied public health social scientist with expertise in health information technology and user-centered design. Dr. Chokshi served as the project manager for this study. Stan Kachnowski, PhD, MPA, CSEP, is the Chair of Healthcare Innovation Technology Lab and has conducted extensive research focused on the efficacy and diffusion of digital health technologies. Dr. Kachnowski served as the Principal Investigator of this study.

S. Kachnowski

Kathleen Lynch, MS is a medical anthropologist with expertise in qualitative research methodologies. Ms. Lynch served as the study coordinator and lead data analyst on this study. Michael P. Frost, MD, FACP, FASAM, is a board-certified addiction medicine physician as well as President, Medical Director, Medical Expert, and Principal Investigator of Frost Medical in Conshohocken, Pennsylvania, where he treats patients with various substance addictions using a holistic approach. Dr. Frost served as site director for this study. Sara Chokshi, DrPH is an applied public health social scientist with expertise in health information technology and user-centered design. Dr. Chokshi served as the project manager for this study. Stan Kachnowski, PhD, MPA, CSEP, is the Chair of Healthcare Innovation Technology Lab and has conducted extensive research focused on the efficacy and diffusion of digital health technologies. Dr. Kachnowski served as the Principal Investigator of this study.