Table 1.

Concentrations of antidepressants (in alphabetical order) in maternal plasma, amniotic fluid, umbilical cord plasma and infant blood.

Antidepressant	Reference	N (n)	Daily dose (mg)	Maternal plasma concentration (ng/mL)	Amniotic fluid concentration (ng/mL)	Umbilical cord plasma concentration (ng/mL)	Breast milk concentration (ng/mL)a		Infant plasma concentration (ng/mL)	Quality score
							Fore-milk	Hind-milk
Amitriptyline	(Bader & Newman, 1980)	1	100	142.0–227.0			187.0–210.0		<10.0	9
	(Brixen-Rasmussen et al., 1982)	1 (1)	25–75	38.0–121.0			60.0–179.0		<20.0	11
	(Pittard & O’Neal, 1986)	1(1)	100	117.0–167.0			77.0–143.0			11
	(Yoshida et al., 1997a)	2 (2)	100–175	128.0–228.0b			30.0b	113.0–197.0b		11
				1443.0–7156.0c			185.0c	707.0–4077.0c
Amoxapine	(Gelenberg, 1979)	1 (1)	250	97.0			<20.0			9
Bupropion	(Briggs et al., 1993)	1 (1)	100	9.0–72.0			58.0–189.0			10
	(Davis et al., 2009)	3 (3)	150–300	13.5–150.0			8.5–11.5			11
	(Fokina et al., 2016)	18 (18)	75–300	0.13–53.7	0.7–48.0	0.22–28.5				14
	(Haas et al., 2004)	10 (10)	300	25.0±24.6			45.2±49.5			14
Citalopram	(Berle et al., 2004)	9 (10)	20–50	18.5–164.9			51.0–235.4		<2.6	12
	(Franssen et al., 2006)	1 (1)	40	113.0–160.1			230.2–320.1		1.2–2.3	8
	(Heikkinen et al., 2002)	9 (9)	20–40	40.3–64.6			90.3–144.5		1.1–9.7	13
	(Hendrick et al., 2003)	4 (4)	20–40	12.0–64.0		17.0–36.0				11
	(Jensen et al., 1997)	1 (1)	20	33.8–60.1			87.7–140.3		2.3	9
	(Laine et al., 2003)	9 (9)	20–40	18.83–69.48		11.36–70.45				13
	(Loughhead et al., 2006a)	1 (1)	50	262.0	94.0					13
	(Paulzen et al., 2017b)	12 (12)	10–40	7.0–84.7	10.1–123.0d	5.1–61.7				14
	(Pogliani et al., 2017)	2 (2)	5–10	9.3–10.1		5.5–14.3				15
	(Rampono et al., 2000)	7 (7)	Unclear	56.0–138.0			53.0–168.0		<2.3	13
	(Rampono et al., 2009)	8 (8)	20–40	8.0–84.0		6.0–71.0				12
	(Schmidt et al., 2000)	1 (1)	20–40	49.0–98.9			205.0		4.5–12.7	8
	(Schoretsaniti s et al., 2019)	6 (6)	10–30	36.4–174.0			41.5–260.0			13
	(Sit et al., 2011)	1 (1)	50	41.4		23.0				14
	(Spigset et al., 1997)	2 (2)	20–40	24.7–69.5			28.6–117.2			12
	(Weisskopf et al., 2017)	1 (1)	20	65.0			123.0	149.0		8
	(Weissman et al., 2004)	2 (2)	20	44.0–63.0			41.0–68.0		<2.1	12
Clomipramine	(Loughhead et al., 2006b)	7 (7)	50–175	27.0–264.0		40.0–190.0				11
	(Schimmell et al., 1991)	1 (1)	125–150	208.4–509.8			215.8–624.2		9.8–266.6	11
	(Yoshida et al., 1997a)	2 (2)	75–125	89.9–198.0b			32.0–212.0b	32.0–432.0b		11
				69.0–400.0c			43.0–200.0c	61.0–283.0c
Desipramine	(Stancer & Reed, 1986)	1 (1)	300	257.0–271.0			316.0–328.0		<1.0	9
Desvenlafaxine	(Rampono et al., 2011)	10 (10)	50–150	142.0–733.0			275.0–1309.0		1.0–37.0	15
Dothiepin	(Buist et al., 1993b)	28 (28)	75–225	15.0–118.0			12.0–140.0			11
	(Ilett et al., 1992)	8 (8)	25–225	11.0–170.0			5.0–207.0	20.0–475.0		15
	(Rees et al., 1976)	1 (1)	75–300	10.0–33.0			10.0–11.0			8
	(Yoshida et al., 1997a)	2 (2)	50–225	27.0–712.0b			54.0–988.0b	121.0–1250.0b		11
				180.0–2623.0c			124.0–3730.0c	309.0–4737.0c
Doxepin	(Frey et al., 1999)	1 (1)	35	60.0			60.0–100.0		<40.0	10
	(Matheson et al., 1985)	1 (1)	75	47.0–87.0			7.0–38.0			7
	(Kemp et al., 1985)	1 (1)	150	136.4±30.0			136.6±27.1	206.2±51.2		10
Duloxetine	(Boyce et al., 2011)	1 (1)	60	151.0–245.0		18.0	50.8		2.0	10
	(Briggs et al., 2009)	1 (1)	60	24.0–53.0		65.0	31.0–64.0		<1.0	10
	(Collin- Levesque et al., 2018)	1 (1)	60	39.7–60.6		16.1	23.6–25.2	14.3–29.3		11
	(Lobo et al., 2008)	6 (6)	80	15.6–63.2			3.9–18.3			15
Escitalopram	(Castberg & Spigset, 2006)	1 (1)	5–10	10.0–37.5			24.9–76.1			11
	(Loughhead et al., 2006a)	1 (1)	5	17.0	3.0					13
	(Rampono et al., 2006)	8 (8)	10–20	9.0–49.0			27.0–99.0			15
	(Rampono et al., 2009)	8 (8)	10–30	4.5–64.0		4.4–54.0				12
	(Sit et al., 2011)	2 (2)	10	5.6–13.5		≤6.7				14
	(Weisskopf et al., 2017)	1 (1)	20	94.0			173.0	195.0		8
Fluoxetine	(Berle et al., 2004)	1 (1)	20	222.4e			66.15		13.95	12
	(Burch & Wells, 1992)	1 (1)	20	265.0–284.0			119.0	30.0		7
	(Hale et al., 2001)	1 (1)	40	875.0			238.0		<182.0	5
	(Heikkinen et al., 2003)	11 (11)	20–40	140.6–233.3			81.5–116.7		6.7–72.4	12
	(Hendrick et al., 2003)	15 (15)	10–60	54.0–553.0		25.0–383.0				11
	(Hendrick et al., 2001)	9 (9)	10–40	64.0–1180			49.0–457.0		<265.0	11
	(Isenberg, 1990)	1 (1)	20	295.0			70.4			6
	(Kim et al., 2006)	30 (30)	10–30	226.3–569.0		239.6	317.0		265.5	12
	(Kristensen et al., 1999)	14 (14)	20–80	108.0–809.0			54.0–705.0			15
	(Laine et al., 2003)	6 (6)	20–40	96.06–209.7e		63.3–110.915				13
	(Loughhead et al., 2006a)	11 (11)	20–80	200.0–872.0	4.0–80.0					13
	(Rampono et al., 2004)	4 (4)	20–40	76.0–451.0		42.0–401.0			32.0–110.0	12
	(Rampono et al., 2009)	2 (2)	20–40	178.0–486.0		136.0–367.0				12
	(Weisskopf et al., 2017)	1 (1)	20	228.0			55.0	46.0		8
	(Weissman et al., 2004)	1 (1)	20	309.0			689.0		13.0	12
	(Yoshida et al., 1998)	4 (4)	20–40	138.0–427.0			39.0–131.0	57.0–177.0	<20.0	11
Fluvoxamine	(Arnold et al., 2000)	1 (1)	75	20.0			24.0–40.0		9.0	9
	(Hostetter et al., 2000)	1 (1)	100–150	7.0–41.0	4.0	5.0				11
	(Kristensen et al., 2002)	2 (2)	50–150	29.7–190.8			35.9–256.3			13
	(Rampono et al., 2009)	1 (1)	150	27.0		21.0				12
	(Sit et al., 2011)	1 (1)	400	62.7		4.9				14
	(Weisskopf et al., 2017)	1 (1)	50	30			23.0	27.0		8
	(Wright et al., 1991)	1 (1)	200	310.0			90.0			10
	(Yoshida et al., 1997b)	1 (1)	100	170.0			50.0			7
Imipramine	(Sovner & Orsulak, 1979)	1 (1)	200	62.0			21.0–59.0			10
	(Yoshida et al., 1997a)	4 (4)	75–150	38.0–360.0b			34.0–408.0b	48.0–622.0b		11
				29.0-340-0c			40.0–509.0c	110.0–610.0c
Mianserin	(Buist et al., 1993a)	2 (2)	40–60	22.0–25.0			20.0–80.0		<10.0	9
Mirtazapine	(Aichhorn et al., 2004)	1 (1)	30	7.0–25.0			7.0–28.0	18.0–34.0		13
	(Kristensen et al., 2007)	8 (8)	30–120	47.0f			53.0			14
	(Tonn et al., 2009)	1 (1)	15	27.0			15.0		10.0	8
Nortriptyline	(Loughhead et al., 2006b)	9 (9)	30–150	2.8–71.3		4.7–66.4				11
	(Matheson & Skjaeraasen, 1988)	1 (1)	75–125	104.0–298.0			90.0–404.0			10
	(Sit et al., 2011)	1 (1)	75	22.6		10.6				14
	(Sjoqvist et al., 1972)	1 (1)	75	1200.0		430.0			180.0	12
Paroxetine	(Begg et al., 1999)	6	20–30	32.2–117.8			19.8–61.7		<4.0	8
		4	10–20	12.0–85.0			4.0–37.0	5.0–42.0	<4.0
	(Berle et al., 2004)	6 (6)	10–30	7.2–69.1			5.9–50.0		<1.6	12
	(Hendrick et al., 2003)	8 (8)	10–40	10.0–59.0		3.0–31.0				11
	(Hendrick et al., 2000)	1 (1)	10	10.0			<2.0		<1.0	7
	(Misri et al., 2000)	23 (23)	10–40	1.1–276.1			1.4–101.8		<0.1	15
	(Loughhead et al., 2006a)	2 (2)	20–40	14.0–39.0	≤3.0					13
	(Oberlander et al., 2004)	33 (33)	10–40	4.4–33.3		1.5–10.9				10
	(Ohman et al., 1999)	7 (7)	10–40	16.0–164.0			8.0–92.0			15
	(Pogliani et al., 2017)	2 (2)	20–25	23.4–48.6		9.1–10.3				15
	(Rampono et al., 2004)	2 (3)	20	10.0–13.0		5.0–7.0				12
	(Rampono et al., 2009)	1 (1)	30	13.0		2.0				15
	(Spigset et al., 1996)	1 (1)	20–40	163.0			7.6			8
	(Weisskopf et al., 2017)	1 (1)	20	27.0			16.0	24.0		8
	(Weissman et al., 2004)	3 (3)	10–30	17.0–77.0			10.0–54.0		<1.5	12
Reboxetine	(Hackett et al., 2006)	4 (4)	4–10	115.0–321.0			6.7–16.3		2.3–5.0	14
Sertraline	(Altshuler et al., 1995)	1 (1)	100	48.0			26.6		<0.5	7
	(Berle et al., 2004)	6 (6)	50–100	14.1–39.4			29.7–70.3		<1.5	12
	(Hendrick et al., 2003)	11 (11)	100–150	3.0–50.0		1.0–14.0				11
	(Hostetter et al., 2000)	1 (1)	150–175	45.0–53.0	<2.0	21.0				11
	(Kristensen et al., 1998)	8 (8)	50–200	15.7–92.0			27.9–193.3		<5.0	15
	(Loughhead et al., 2006a)	5 (5)	50–250	52.0–248.0	≤25.0					13
	(Paulzen et al., 2017a)	6 (6)	25–100	9.7–30.1	4.0–14.0	3.1–9.3				13
	(Pogliani et al., 2017)	10 (10)	25–100	7.4–89.0		<5.0–35.5				15
	(Rampono et al., 2004)	4 (4)	50	9.0–64.0		5.0–24.0				12
	(Rampono et al., 2009)	5 (5)	25–100	4.0–53.0		1.0–22.0				15
	(Schoretsaniti s et al., 2019)	6 (6)	25–100	3.3–17.8			3.6–35.7			13
	(Sit et al., 2011)	9 (9)	50–200	5.8–32.4		2.7–11.0				14
	(Stowe et al., 1997)	26 (26)	25–250	12.0–206.0			8.4–290.0		≤87.0	11
	(Stowe et al., 2003)	12 (12)	25–200	8.0–92.0			17.0–173.0		≤3.0	11
	(Weisskopf et al., 2017)	1 (1)	50	29.0			29.0	46.0		8
	(Weissman et al., 2004)	20 (20)	50–100	10.0–42.0			12.0–90.0		<1.5	12
Venlafaxine	(Paulzen et al., 2020)	9 (9)	37.5–225	33.9–338.0	309.5–1052.5	21.1–448.4				15
	(Berle et al., 2004)	3 (3)	75–225	110.0–387.0e			273.5–865.7e		8.4–34.6e	12
	(Boucher et al., 2009)	7 (7)	37.5–300	7.8–26.1		1.4–638.0			5.8–163.7	12
	(Hostetter et al., 2000)	1 (2)	200–300	432.0	329.0	879.0–887.0				11
	(Ilett et al., 1998)	1 (1)	150	231.0			940.0			12
	(Ilett et al., 2002)	6 (6)	225–300	264.9–600.7			856.0–1464.0			15
	(Loughhead et al., 2006a)	3 (3)	150–225	169.0–452.0	146.0–1792.0					13
	(Newport et al., 2009)	11 (11)	112.5–300	292.0–1210.0			739.2–2231.3		<4.0–248.0	12
	(Pogliani et al., 2017)	1 (1)	150	199.8		78.9				15
	(Rampono et al., 2004)	1 (1)	150	612.0		638.0				12
	(Rampono et al., 2009)	10 (10)	75–450	64.0–2283.0		64.0–1694.0				15
	(Schoretsaniti s et al., 2019)	5 (5)	37.5–150	94.0–462.0			79.5–1086.0			13
	(Sit et al., 2011)	2 (2)	75	156.4–216.3		124.6–151.4				14

N: number of patients; n: number of infants. For amitriptyline, clomipramine, doxepin, fluoxetine, imipramine and venlafaxine provided levels refer to active moiety, i.e. the sum of parent compound and active metabolite. The quality score column represents the quality scores assigned to the study using the ClinPK checklist (for details, see Supplementary table 2).

^aOne value is provided, when authors did not specify fore-milk or hind-milk.

^bMeasured by gas chromatography.

^cMeasured by enzyme immunoassay.

^dValues were converted from nmol/L using a conversion factor (CF) of 3.3, fairly close to 3.23 (CF for fluoxetine) and 3.39 (CF for N-desmethyl-fluoxetine)

^eValues were converted from nmol/L using a conversion factor (CF) of 3.7, fairly close to 3.61 (CF for venlafaxine) and 3.80 (CF for O-desmethyl-venlafaxine)

^fFor 7 patients