Table 1. Review of current buprenorphine dosing guidelines in the literature.

Scoping review of existing literature buprenorphine dosing through the perinatal period organized by category of study (randomized controlled trials, cohort, case control, observational, and case studies). For each citation, we discuss the demographics of their participants, formulation of buprenorphine used (including mono vs combination product, tab vs film administration), buprenorphine dosing frequency, dose reported during pregnancy, at delivery, and during postpartum, as well as changes in dosing discussed in each study

Study citation	Population demographics	Formulation (dosing frequency, route of administration)	Dose during pregnancy (mean, mg/day)	Dose at delivery (mean, mg/day)	Dose postpartum (mean, mg/day)	Changes in dose
Randomized controlled trials
Fischer et al. (2006)	18 women randomized to buprenorphine group (n=9) or methadone (n=9) mean age of buprenorphine group: 26.2yo mean EGA at enrollment of buprenorphine group: 24.0wk study duration: 18.5wk Addiction Clinic at Medical University of Vienna, Vienna, Austria	“flexible” dosing sublingual buprenorphine tablets w/ matched placebo	at end of induction period: 13.5 during third trimester (T3): 14.0	14.0	Not reported	from induction to T3: +0.5 mg/day from induction to delivery: +0.5 mg/day
Cohort studies
Lo-Ciganic et al. (2019)	2363 women mean age: 27.8yo 95% white categorized into early initiators w/ persistently high adherence (EIwPHA, n=747), moderate-to-high adherence (EIwMtHA, n=357), declining adherence over time (EIwDA, n=248), early discharge before T3 (EIwED, n=393), late initiators w/ mod-to-high adherence (LIwMtHA, n=318), late initiators w/ low-to-mod adherence (LIwLtMA, n=298) Pennsylvania Medicaid	sublingual buprenorphine or buprenorphine-naloxone	During first trimester (T1): EIwPHA: 17.4 EIwMtHA: 13.3 EIwDA: 16.6 EIwED: 12.6 Overall during pregnancy: EIwPHA: 17.6 EIwMtHA: 15.7 EIwDA: 16.5 EIwED: 15.5 LIwMtHA: 15.3 LIwLtMA: 14.7	Not reported	Not reported, though the study did follow women through 12 weeks postpartum	not reported from pregnancy to postpartum from T1 to pregnancy overall: EIwPHA: +0.2 mg/day EIwMtHA: +2.4 mg/day EIwDA: −0.1 mg/day EIwED: +2.9 mg/day from T1 to overall for all groups with >1 data point: +1.2 mg/day
Brogly et al. (2018)	59 women mean age: 28yo 80.5% white divided into group that had initiated treatment prior to conception (PTC, n=20) and group that initiated prenatally (PN, n=39) Project RESPECT clinic (2015–16), Boston Medical Center	once daily buprenorphine	At pregnancy initiation: PTC: 16.2 PN: 10.4	14.7	Not reported	not reported from pregnancy to postpartum from initiation to delivery: PTC: −1.5 mg/day PN: +4.3 mg/day
Coker et al. (2018)	64 women mean age: 28.4yo mean EGA at enrollment: 20.88wk categorized as adherent (n=41), moderately adherent (n=8), nonadherent (n=15) Women’s Mental Health Program at Univ of Arkansas	once daily buprenorphine	Overall at last visit: 14.98 moderately adherent: 14 nonadherent: 10	See other 2 columns	Adherent at last visit: 17	Overall for adherent: +7 mg/day
O’Connor et al. (2018)	190 women 95% Caucasian divided into still in treatment at 6 mos postpartum (S6, n=151), 12 mos postpartum (S12, n=135) and not in treatment at 6 mos postpartum (N6, n=39), 12 mos postpartum (N12, n=55) rural Maine	buprenorphine monotherapy during pregnancy transitioned to combination buprenorphine-naloxone at first refill in postpartum period	Not reported prior to delivery	S6: 15.1 N6: 14.0 S12: 15.3 N12: 14.3	Not reported, though changes to postpartum reported in next column	S6: 51.3% at same dose as at delivery 15.9% increase (mean: +4.94 mg/day) 32.5% decrease (mean: −4.55 mg/day) S12: 36.3% on same dose as delivery 15.6% increase (mean: +4.31 mg/day) 48.1% decrease (mean: −5.15 mg/day)
Welle-Strand et al. (2015)	123 women: 43 on buprenorphine, 80 on methadone divided into group that tapered dose >50% (TD50, n=7), group that tapered dose 11–50% (TD11, n=12), group that was stable or had increased dose (SoID, n=24) Norway	Buprenorphine	At pregnancy determination: TD50: 14.6 TD11: 17.8 SoID: 15.6 Lowest dose during pregnancy: TD50: 1.7 TD11: 11.4 SoID: 12.8	TD50: 2.3 TD11: 12.3 SoID: 17.8	Not reported	From pregnancy determination to delivery: TD50: −12.3 mg/day TD11: −5.5 mg/day SoID: +2.2 mg/day
Simmat-Durand et al. (2009)	159 women mean age: 28.4yo 92% French citizens divided into group with no social disadvantage (NSD, n=64) and group with social disadvantage (SD, n=95) 35 hospitals in France	once daily buprenorphine	Overall during “early pregnancy”: 6.9 NSD: 7 SD: 6.78	Overall: 5.4 NSD: 5.03 SD: 5.66	Not reported	not reported from pregnancy to postpartum from “early pregnancy” to delivery: −1.5 mg/day 40% of participants had decreased dose during pregnancy, while 34% maintained same dose
Kahila et al. (2007)	67 women mean age: 24.6yo categorized into 3 groups based on perceived compliance: compliant (A, n=9), non-compliant (B, n=37), maintenance (C, n=21) Finland	once daily sublingual buprenorphine	At start (<18 wk estimated gestational age, EGA): A: 4.9 B: 5.9 C: 10.9 At 18wk EGA: A : 1.9 B: 4.1 C: 10.9 At 24wk EGA: A : 1.1 B: 4.3 C: 10.2 At 30wk EGA: A: 0.9 B: 4.9 C: 8.6 At 36wk EGA: A: 0.1 B: 3.4 C: 4.9	A: 0 B: 4.1 C: 6.5	Not reported	overall median change from study start to day of delivery: −2.3 mg/day
Case control studies
Concheiro et al. (2010)	5 women mean age 30.6yo mean EGA at admission: 23.0 100% African American Center for Addiction and Pregnancy Johns Hopkins, Baltimore, MD	once daily sublingual buprenorphine HCl tablets + 40 mL liquid placebo	overall: 15.2 during T3: 16.6 during last month of pregnancy: 18.4	18.4	Not reported	not reported from pregnancy to postpartum overall to delivery: +3.2 mg/day from T3 to last month: +1.8 mg/day
Observational studies
Bastian et al. (2017)	13 women evaluated in T2 (PK-2, n=7), T3 (PK-3, n=11), and postpartum (PK-P, n=10) mean age of participants: PK-2: 27.3yo PK-3: 27.9yo PK-P: 28.6yo Magee-Women’s Hospital, Pittsburgh, PA	twice daily sublingual buprenorphine tablets	PK-2: 16.0 PK-3: 20.0	Not reported	mean timing of postpartum testing: 7.4wks after delivery PK-P: 16.0	from PK-2 to PK-3: + 2.0 mg BID (total +4.0 mg/day) from PK-3 to PK-P: −2.0 mg BID (total −4.0 mg/day)
Caritis et al. (2017)	14 women evaluated in T2 (n=7), T3 (n=11) and postpartum (PP, n=10) mean age of participants: T2:27yo T3: 28yo PP:29yo Magee-Womens Hospital Pregnancy Recovery Center (PRC)	twice daily sublingual buprenorphine	T2: 8 T3: 10	Not reported	mean timing of postpartum testing: 7wk after delivery PP: 16	from T2 to T3: +2 mg BID (total +4 mg/day) from T3 to 7wk PP: −2 mg BID (total −4 mg/day)
Concheiro et al. (2011)	3 women completed through 2 months postpartum (PP) mean age: 30yo 100% black Center for Addiction and Pregnancy Johns Hopkins, Baltimore, MD	once daily sublingual buprenorphine tablets + 40 mL cherry-flavored placebo liquid	collected during week 28 or 29 and week 34 of gestation overall: 15.7 during gestational wk 28/29: 14.6 mean during gestational wk 34: 16.6	Not reported	mean timing of postpartum testing: 2 mos after delivery PP: 18.6	from gestational wk 28–34: +2 mg/day from gestational wk 34 to 2 mos PP: +2 mg/day
Ilett et al. (2011)	7 women mean age: 31yo King Edward Memorial Hospital, Subiaco, WA, Australia	once daily 1 subject was twice daily at study start but was transitioned to once daily sublingual buprenorphine tablets	Not reported	Not reported	tested at 3wks after delivery mean: 7	Not reported
Lacroix et al. (2011)	90 women on buprenorphine 45 women on methadone mean age of buprenorphine group: 30yo France	buprenorphine	at “beginning of pregnancy”: 6.3 at “end of pregnancy”: 5.1	Not reported	Not reported	not reported from pregnancy to postpartum from “beginning” to “end” of pregnancy: −1.2 mg/day
O’Connor et al. (2011)	23 women mean age of participants at delivery: 25.8yo	Buprenorphine	T1: 7.9 T2: 11.1	13.3	Not reported	70% required dose increases over course of pregnancy: +5.9 mg/day
Kacinko et al. (2009)	9 women mean age: 30.0yo mean EGA at admission: 22.8wk 8 African-American, 1 white Center for Addiction and Pregnancy Johns Hopkins, Baltimore, MD	once daily buprenorphine HCl sublingual tablets + 40mL placebo cherry-flavored liquid	overall: 15.4 T2: 12.8 T3: 15.8	18.6	17.4	dose difference: T2 < T3 < postpartum between T2 and postpartum: +4.6 mg/day
Lindelman et al. (2009)	7 women median age: 31yo median BMI: 20.8 median 6 weeks EGA Karolinska University Hospital, Huddinge (Stockholm, Sweden); Maria Addiction Centre	once daily 1 subject was three times daily sublingual buprenorphine	median at study start (measured in mg/kg/day): 0.32	Not reported	measured at 5–8 days postpartum (except in 1 case at 270 days) at a median 6 days, mean 43.7 days median dose (mg/kg/day) : 0.29	median change between start and postpartum (mg/kg/day): −0.3 mean change between start and postpartum (mg/kg/day): −0.2
Kacinko et al. (2008)	9 women mean age: 30.0yo mean EGA at admission: 22.8wk 8 African-American, 1 Caucasian	once daily sublingual buprenorphine HCl + placebo tablets + 40 mL liquid placebo	overall: 15.0 in T3: 16.1	18.7	Not reported	not reported from pregnancy to postpartum from start to T3: +1.1 mg/day from start to delivery: +3.7 mg/day
Goodwin et al. (2007)	9 women mean age: 30yo 8 African-American, 1 white Center for Addiction and Pregnancy, Johns Hopkins, Baltimore, MD	once daily sublingual buprenorphine	Initial: 8.2	18.7	Not reported, though does note that participants were maintained “up to 10 wks after delivery”	not reported from pregnancy to postpartum from initial dose to delivery: +10.5 mg/day
Lacroix et al. (2004)	34 women mean age: 31yo mean EGA: 142d	once daily sublingual Buprenorphine tablets	during “early pregnancy”: 6.6 “at end of pregnancy”: 3.9	Not reported	Not reported	not reported from pregnancy to postpartum from “early” to “end of’ pregnancy: −2.7 mg/day
Johnson et al. (2001)	3 women mean age: 26.3yo mean EGA at admission: 25wk 100% African-American	once daily sublingual buprenorphine tablets	Throughout pregnancy: 9.3	9.3	After delivery: women were maintained on buprenorphi ne ×21 days, then tapered off either with 21-day inpatient or 10-wk outpatient schedule	From pregnancy to 13wks postpartum: −9.3 mg/day (due to study design—postpartum taper)
Fischer et al. (2000)	15 women mean age: 24.0yo mean EGA at enrollment: 27.9wk drug addiction outpatient clinic, Department of General Psychiatry, Univ of Vienna, Vienna, Austria	once daily sublingual buprenorphine tablets	At induction: 8.4	7.4	Not reported	not reported from pregnancy to postpartum from induction to delivery: −1.0 mg/day
Fischer et al. (1998)	9 women mean age: 24.0yo mean EGA at first contact: 15.4wk drug addiction outpatient clinic at University Hospital of Psychiatry	once daily buprenorphine	8.1	8.1	Not reported	throughout pregnancy: 0 mg/day
Case report/series
Ross. (2004)	1 woman 24yo primigravida Access Drug and Alcohol Clinic, Birralee Maternity Services, Box Hill Hospital, Victoria, Australia	Buprenorphine	During “later stage of pregnancy, up to day of induction”: 34	34	Not reported	Not reported, though paper does insinuate that patient’s dose increased during pregnancy
Schindler et al. (2003)	2 women both Caucasian	once daily buprenorphine	9	9	Not reported	From conception to delivery: 0 mg/day