Background Current knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant. Materials and methods In this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11–33) months versus 36 (20–48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics. Results At follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008). Conclusions Chronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.