Reddit discussions about buprenorphine associated precipitated withdrawal in the era of fentanyl

Figures & data

Figure 1. Flow diagram illustrating the extraction, analyses, and steps included in this study, along with the number of posts included where relevant. Starting with a set of predetermined key phrases (a), we generated their lexical variants (b) and computed their frequencies in data from the seven included subreddits (c). Posts about precipitated withdrawal and Bernese method were filtered (d) and manually coded for themes (e). Topics of interest were discovered during the manual coding (f) and natural language processing methods were applied to retrieve more posts related to the topics (g). Descriptive analyses were performed on the retrieved posts (h). NLP: natural language processing.

Table 1. Codes for manual characterization, their definitions. Examples are provided in Table A3 of the Supplementary material.

Code	Definition
Non-Opioid Treatment of POW	Discussion of use of kratom, LSD, loperamide, ondansetron, mushrooms, clonidine to manage withdrawal symptoms
Avoidance and Fear of POW	Discussion of how precipitated withdrawal might be worse then regular withdrawal
Buprenorphine dosing Strategies	Discussion specific milligram and frequency of Buprenorphine doses
Specific Triggers of POW	Discussion of specific experiences of POW, for example having POW X amount of hours after last use
Personal Experience with buprenorphine microdosing strategies	Discussion of positive or negative experiences with microdosing, beyond specific recommendations for dosages
Experience of Opioid Use Disorder	Discussion of use of fentanyl, heroin, oral opioids, prior remission of OUD
Buprenorphine pharmacology	Discussion of buprenorphine pharmacology such as partial agonist activity and naloxone component of suboxone
Fentanyl Pharmacology	Discussion of fentanyl pharmacology such as lipophilicity and length of action
Other/none of the above	Posts that cannot be categorized into any of the above themes

Figure 2. Yearly distributions of mentions of precipitated withdrawal (top), fentanyl and analogs (middle), and Bernese method (bottom) within our chosen six subreddits. Counts of distinct lexical variants are aggregated. For 2021, the values presented are estimates based on the number of days that had elapsed up to the day of collection (April 23; 113 days). The true count is multiplied by the fraction $\frac{365}{113}.$

Table 2. Distribution of manually-assigned codes in the sample of precipitated withdrawal and Bernese method reviewed.

Code	Distribution in precipitated withdrawal posts (n = 384)	Distribution in Bernese method posts (n = 106)
Non-Opioid Treatment of POW	26 [6.7%]	14 [13.2%]
Avoidance and Fear of POW	77 [20.0%]	10 [9.4%]
Buprenorphine dosing Strategies	140 [36.5%]	47 [44.3%]
Specific Triggers of POW	232 [60.4%]	38 [35.8%]
Personal Experience with Buprenorphine microdosing strategies	14 [3.6%]	33 [31.1%]
Experience of Opioid Use Disorder	134 [34.9%]	43 [40.6%]
Buprenorphine pharmacology	60 [15.6%]	12 [11.3%]
Fentanyl Pharmacology	32 [8.3%]	7 [6.6%]
Other/None of the above	32 [8.3%]	0 [0%]
Recommendation of Bernese Method without further context	0 [0%]	36 [34.0%]

Figure 3. Boxplots showing the distributions of time between last opioid use to buprenorphine initiation that led to precipitated withdrawal for fentanyl & analogs, heroin and unspecified opioids.

Table 3. Buprenorphine microdosing regimens discussed on subreddits.

Dosing regimen	Total duration described
Day 1 & 2: 0.5 mg buprenorphine	6 days
Day 3 & 4: 1 mg buprenorphine
Day 5 & 6: 2 mg buprenorphine
Start with 0.5 mg and increase [to full dose] over ∼5 days	5 days
Start with 0.25 mg and increase slowly [to full dose] over the next few days	Unspecified
Day 1: 0.125 mg	Unspecified
Day 2: 0.15 mg
Day 3: 0.2 mg
Increase gradually
Day 1: 0.25 mg $\times$ 4	Unspecified
Day 2: 0.5 mg $\times$ 4
Increase proportionally until prescribed dose of Suboxone^®; continue opioid use in the meantime.
Increase [from 1 mg] to 8 mg in 8 days	8 days
Wait until standard opioid withdrawal becomes too difficult to tolerate and then take a small dose (0.5 mg) of buprenorphine. If precipitated withdrawal starts, take opioid. Increase Suboxone^® and lower opioid over time gradually.	Unspecified
Day 1: 0.5 mg buprenorphine while continuing fentanyl use	6 days
Day 2: 1 mg $\times$ 2
Day 3: 2 mg $\times$ 2
Day 4: 4 mg $\times$ 2
Day 5: 8 mg $\times$ 2
Day 6: 8 mg $\times$ 2, but without opioid/fentanyl/oxycodone
Day 1: 0.5 mg $\times$ 2 (AM/PM); use fentanyl after Suboxone^® dose, just enough to feel okay.	6 days
Day 2: 1 mg $\times$ 2 (AM/PM); same amount of fentanyl as day 1.
Day 3: 2 mg $\times$ 2 (AM/PM); only use fentanyl if feeling sick and do not use extra fentanyl.
Day 4: 4 mg AM; no fentanyl
Day 5: no Suboxone^® and no fentanyl
Day 6: 4 mg Suboxone^®; no fentanyl
Wait as long as possible after fentanyl use until withdrawal starts. Then take 1 mg Suboxone^®. Use fentanyl if precipitated withdrawal occurs. Follow this routine for a week, 2 times a day, while slowly increasing Suboxone^® dose.	7 days
Day 1: 0.5 mg buprenorphine in the morning; wait half an hour before using opioid again. Repeat same routine in the evening.	Unspecified
Day 2: 1 mg $\times$ 2 (morning/evening); lower dose of opioid.
Repeat method by increasing buprenorphine and reducing opioid amounts over time.