Table 2.

Antidepressant Drug Therapy in Breastfeeding Mothers: Infant Serum Drug Levels and Behavioral Outcomes

StudyNo. of InfantsMaternal DoseInfant Age (weeks)Infant Serum Drug Levels (Lower Limit of Detection)*Adverse Infant-Related Clinical Outcomes
Selective Serotonin Reuptake Inhibitors (SSRIs)
 Citalopram (Celexa)
  Jensen et al, 199723120 mg/day87 ng/mLNone
  Schmidt et al, 200024140 mg/day612.7 ng/mLUneasy sleep, normalized with dose reduction
  Rampono et al, 20002570.36 mg/kg/day (median)Not detected; 2.3 ng/mL (1 ng/mL)None
  Spigset et al, 199726320–40 mg/day8–16Not discussedNone
 Fluoxetine (Prozac)
  Brent & Wisner, 199827120 mg/day2–361 ng/mLLimp, unresponsive, cyanotic (mother also taking carbamazepine and buspirone)
  Burch & Wells, 199228120 mg/day17Not discussedNone
  Chambers et al, 19992964Not given2–24Not discussedLower growth curves (average deficit of 392 g)
  Hendrick et al, 2001302010–60 mg/day0–31Fluoxetine, <1–84 ng/mL; Norfluoxetine, <1 - 265 ng/mL (2 ng/mL)None
  Isenberg, 199031120 mg/day20Not discussedIrritability
  Kristensen et al, 199932140.24–0.94 mg/kg/day0–60Not detected; 252 ng/mL (10 ng/mL)Colic in 2 infants; irritability, crying, and poor feeding in 2 infants (one of these also had methadone exposure)
  Lester et al, 199333120 mg/day24Fluoxetine, 340 ng/mL; Norfluoxetine, 208 ng/mLCrying, vomiting, diarrhea, and decreased sleep, problem reversed with formula feeding
  Taddio et al, 199634110.17–0.85 mg/kg/day3–107Not detected in the one infant sampled (1 ng/mL)None
  Yoshida et al, 199835420–40 mg/day4–40Fluoxetine and nonfluoxetine not detectable (2 ng/mL)None
 Fluvoxamine (Luvox)
  Hendrick et al, 2001365100–150 mg/day6–13Not detected (1 ng/mL)None
  Piontek, 2001372300 mg/day2–8Not detected (2.5 ng/mL)None, for up to 2–3 years after exposure
  Wright et al, 1991381200 mg/day12Not discussedNone
  Yoshida et al, 1997391100–200 mg/day17Not discussedNone
 Paroxetine (Paxil)
  Hendrick et al, 200136165–30 mg/day2–26Not detected (1 ng/mL)None
  Misri et al, 2000402310–40 mg/day4–42Not detected (0.1 ng/mL)None
  Ohman et al, 199941710–40 mg/day6–30Not discussedNone
  Stowe et al, 2000421610–50 mg/day4–55Not detected (2 ng/mL)None
 Sertraline (Zoloft)
  Altshuler et al, 1995431100 mg/day3–7Not detected (0.5 ng/mL)None
  Dodd et al, 2001441050–150 mg/dayNot detected (2 ng/mL)None
  Epperson et al, 2001451425–200 mg/day17–26Not detected (2.5 ng/mL)None
  Hendrick et al, 2001363325–200 mg/day2–60Not detected in 28; 2–8 ng/mL in 2 (1 ng/mL)None
  Holland, 2000466Not discussed12–16Not discussedReduced breast milk supply
  Stowe et al, 1997471125–150 mg/day4–141Sertraline, undetectable or <3 ng/mL; desmethyl-sertraline, undetectable or <10 ng/mL (1 ng/mL)None
  Wisner et al, 199848950–200 mg/day0–22Sertraline, not detected or <64 ng/mL; N-desmethyl-sertraline, not detected or <68 ng/mL (2 ng/mL)None
Tricyclic Antidepressants (TCAs)
 Amitriptyline (Elavil)
  Bader & Newman, 1980491100 mg/day7Not detected (10 ng/mL)Not discussed
  Breyer-Pfaff et al, 1995501175 mg/day0–4Not detected (5 ng/mL)None
  Brixen-Rasmussen et al, 198251175–100 mg/day14–30Not detected (5 ng/mL)None
  Erickson et al, 1979521150 mg/day8–11Not detected (28 ng/mL)Not discussed
  Pittard & O’Neal, 1986531100 mg/day2–3Not discussedNot discussed
  Yoshida et al, 1997542100–175 mg/day4–34Not detected in one, 7.5 ng/mL in one (0.1 ng/mL)Probably none (1 infant was hypotonic before and after exposure)
 Clomipramine (Anafranil)
  Schimmell et al, 1991551125 mg/day1–59.8–45.4 (20 ng/mL)None
  Wisner et al, 199556475–125 mg/day2–19Not detected or not quantifiable (10 ng/mL)None
  Yoshida et al, 199754275–125 mg/day20–56Not detected in one; 3.2–5.5 ng/mL in one (0.1 ng/mL)None
 Desipramine (Norpramin)
  Stancer & Reed, 1986571300 mg/day10–11Not detected (1 ng/mL)None
 Doxepin (Sinequan)
  Frey et al, 199958135 mg/day1Doxepin, 10 μg/L; N-desmethyldoxepin not detected (10 ng/mL)Poor suckling and swallowing, drowsiness, hypotonia, vomiting, weight loss
  Kemp et al, 1985591150 mg/day6Not detected (5 ng/mL)None
  Matheson et al, 198560175 mg/day8Doxepin, 3 μg/L; N-desmethyldoxepin, 58–66 μg/L (7 ng/mL)Sedation, respiratory depression
 Imipramine (Tofranil)
  Erickson et al, 1979521150 mg/day8Not detected (28 ng/mL)Not discussed
  Sovner & Orsulak, 1979611200 mg/day4Not discussedNone
  Yoshida et al, 199754475–150 mg/day2–25Not detected in 2; 0.6–7.4 ng/mL in two (0.1 ng/mL)None
 Nortriptyline (Pamelor)
  Altshuler et al, 1995431125 mg/day3–7Not detected (10 ng/mL)None
  Mammen et al, 1997622Not discussed16–31Nortriptyline not detected; E-10-hydroxynortriptyline, <4 (2 ng/mL)None
  Matheson & Skjaeraasen, 198863175–100 mg/day1Not discussedNone
  Wisner & Perel, 199164750–80 mg/day0–24Nortriptyline, not detectable; 10-hydroxynortriptyline, 5–11 ng/mL in 2 infants (4–5 ng/mL)None
  Wisner & Perel, 199665575–110 mg/day4–10Not detected (<4 ng/mL)None
  Wisner et al, 199766760–150 mg/day4–60–10 ng/mL in 6 term infants; 16 ng/mL in the single preterm infant (4 ng/mL)None
Other Antidepressants
 Buproprion (Wellbutrin)
  Briggs et al, 1993671100 mg/day56Not detected (25 ng/mL)None
 Nefazodone (Serzone)
  Yapp et al, 2000681300 mg/day7–101270 ng/mL (lower limits of detection not given)Drowsiness, lethargy, hypothermia, and poor feeding (preterm infant)
 Venlafaxine (Effexor)
  Ilett et al, 19986933–8 mg/kg/day2–24Venlafaxine, not detected (4 ng/mL); O-desmethyl-venlafaxine, 23–225 ng/mL (3 ng/mL)None
  Ilett et al, 2002707225–300 mg/day11–41Venlafaxine, not detected; 5 ng/mL; O-desmethyl-venlafaxine, 1.5–5.7 ng/mL (1 ng/mL)None

  • * Lower limits of detection are shown in parentheses (in nanograms per milliliter) when the specified drug was not detected in the infant’s serum. Lower limits vary with the precision of the laboratory method. ‘Safe’ infant serum levels of antidepressants have not been established, in that safety profiles depend on the age of the infant (healthy term infants more than 10 weeks old have a lower risk of negative effects), the characteristics of the drug, and concentrations of its metabolites.13