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Research ArticleOriginal Article

The Effectiveness of Various Postpartum Depression Treatments and the Impact of Antidepressant Drugs on Nursing Infants

Dwenda Gjerdingen
The Journal of the American Board of Family Practice September 2003, 16 (5) 372-382; DOI: https://doi.org/10.3122/jabfm.16.5.372
Dwenda Gjerdingen
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    Table 1.

    Symptoms and Diagnostic Criteria for Major Depressive Episode

    Symptoms
    1. Depressed mood most of the day.

    2. Markedly diminished interest or pleasure in all, or almost all, activities, most of the day.

    3. Marked decrease or increase in appetite, resulting in significant unintentional weight loss or weight gain (ie, >5% body weight in 1 month).

    4. Insomnia or hypersomnia .

    5. Psychomotor agitation or retardation .

    6. Fatigue or loss of energy.

    7. Feelings of worthlessness or inappropriate guilt.

    8. Decreased ability to think or concentrate.

    9. Recurrent thoughts of death, or recurrent suicidal thoughts (with or without a plan).

    Diagnostic Criteria
    • Five or more of the symptoms listed above, representing a change in baseline, present nearly every day for the same 2-week period, and producing clinically significant distress or change in functioning

    • Must include symptom 1 or 2.

    • Symptoms do not meet criteria for a mixed episode, and they are not due to drugs, another medical condition, or bereavement (unless prolonged; i.e., >2 months)

    • Adapted from Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994.

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    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

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    Table 3.

    Effects of Individual and Group Psychotherapy on Postpartum Depression

    StudyStudy design; nInterventionOutcome
    Individual Therapy
     Appleby et al, 199721Randomized controlled trial; n = 87 women with PPD4 treatment groups: fluoxetine or placebo, plus 1 or 6 sessions of counseling provided by trained health visitors and derived from cognitive behavioral therapy (included reassurance and practical advice about feelings of not coping, child care, and lack of enjoyable activities and practical support)Six sessions of counseling were better than 1 (clinical interview schedule score difference = 38.7% at 12 weeks), and fluoxetine was better than placebo (score difference = 40.7% at 12 weeks). There was no advantage in combining fluoxetine and counseling
     Cooper & Murray, 199780Randomized controlled trial; n = 194 primiparous women with PPD4 treatment groups: nondirective counseling (n = 48), cognitive-behavioral therapy (n = 42), dynamic psychotherapy (n = 48), and a control group (n = 54); therapy sessions occurred 1 hour/week for 10 weeksOver the initial 10-week period, the 3 treatment groups showed greater improvement than the control group; however, by 9 months postpartum, there was no significant difference between groups
     Holden et al, 198981Randomized controlled trial; n = 55 women with PPD8 weekly counseling visits by health visitors trained to provide nondirective counseling (listening to clients’ feelings, and encouraging them to make decisions based on their own judgment)69% of women in the counseling group versus 38% in the control group had recovered after 3 months.
     O’Hara et al, 200082Randomized controlled trial; n = 120 women with PPD12 weekly individual counseling sessions led by experienced psychotherapists (discussed losses & and interpersonal conflicts and affirmed clients’ competence)43.8% of women in the counseling group versus 13.7% controls had recovered after 3 months.
    Group Therapy
     Chen et al, 200083Randomized controlled trial; n = 60 women with PPD4 weekly supportive group sessions comprising discussions about transition to motherhood, postpartum stress management, communication skills, life planning, and strategies for changeIntervention group members experienced significant declines in depression scores, whereas control group members did not (Beck Depression Inventory change: −6.14 versus −0.92, P < .01).
     Fleming et al, 199284Non-randomized controlled trial; n = 76 depressed & 76 non-depressed mothers8 weekly unstructured support groups, facilitated by psychologists; mothers discussed childbirth experiences, mood, motherhood, changing spousal relationships, and returning to work versus staying homeWhile the entire sample showed an improvement in mood from 2 weeks to 5 months postpartum, there was no significant intervention effect.
     Meager & Milgrom, 199685Randomized controlled trial; n = 20 mothers with PPD10-week group treatment program, included education (about PPD), cognitive-behavioral therapy, and homework for reinforcementDepression scores dropped significantly in the experimental group (Edinburgh Postnatal Depression Scale difference: −9.0), but not in the control group (difference, 0.5).
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The Journal of the American Board of Family Practice: 16 (5)
The Journal of the American Board of Family Practice
Vol. 16, Issue 5
1 Sep 2003
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The Effectiveness of Various Postpartum Depression Treatments and the Impact of Antidepressant Drugs on Nursing Infants
Dwenda Gjerdingen
The Journal of the American Board of Family Practice Sep 2003, 16 (5) 372-382; DOI: 10.3122/jabfm.16.5.372

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The Effectiveness of Various Postpartum Depression Treatments and the Impact of Antidepressant Drugs on Nursing Infants
Dwenda Gjerdingen
The Journal of the American Board of Family Practice Sep 2003, 16 (5) 372-382; DOI: 10.3122/jabfm.16.5.372
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