To critically review the literature on use of antidepressants during breast-feeding.

MEDLINE was searched from 1966 to 1995 using the individual names of all antidepressant drugs used during lactation or breast-feeding.

Study designs of evaluations included in the review

Single case studies or case series were included.

Specific interventions included in the review

Amitriptyline, nortriptyline, desipramine, clomipramine, doxepin, dothiepin, fluoxetine, sertraline, and bupropion.

Participants included in the review

Breast-feeding mothers and their infants were included. In the included studies, the infants' ages ranged from 1 to 60 weeks.

Outcomes assessed in the review

Maternal and infant serum levels of drugs and drug metabolites (ng/ml) were measured.

How were decisions on the relevance of primary studies made?

The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.

The authors do not state that they assessed validity.

The authors do not state how the data were extracted for the review, or how many of the authors performed the data extraction.

How were the studies combined?

The studies were combined by a narrative review.

How were differences between studies investigated?

Differences in outcomes between the studies were not investigated statistically.

Fifteen studies representing data from 29 breast-feeding mother-infant pairs were included.

Amitriptyline, nortriptyline, desipramine, clomipramine, dothiepin and sertraline were not found in quantifiable amounts in nurslings, and no adverse effects were reported. With the exception of dothiepin, tricyclic parent drugs were not detectable at levels as low as 1 to 10 ng/ml in nursling serum. For other drugs the limits of detection were: amitriptyline, 5 ng/ml; nortriptyline, 4 to 5 ng/ml; desipramine, 1 ng/ml; clomipramine, 10 ng/ml; and dothiepin, 2 ng/ml. Adverse effects were described in some young infants whose mothers had been treated with doxepin or fluoxetine during breast-feeding.

Amitriptyline, nortriptyline, desipramine, clomipramine, dothiepin and sertraline were not found in quantifiable amounts. Therefore, these are the drugs of choice for breast-feeding women. Adverse effects were described in some young infants whose mothers had been treated with doxepin or fluoxetine during breast-feeding. The collective serum level data suggest that infants older than 10 weeks are at low risk for adverse effects of tricyclics, and there is no evidence of accumulation.

The review is mainly limited by the primary studies: these studies are so small (the largest has seven mothers) that a convincing investigation of the risk of infrequent side-effects is difficult. The literature search is restricted to MEDLINE; a wider search strategy (including a search of bibliographies of retrieved studies) may have retrieved more primary research. Therefore, the results regarding safety could be viewed as inconclusive.

National Institute of Mental Health, grant number MH-53735; Clinical Research Center for Affective Disorders, grant number MH-30915.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.