title: Clomipramine concentration and withdrawal symptoms in 10 neonates.
abstract: OBJECTIVE
  After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up.
  
  
  METHODS
  Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth.
  
  
  RESULTS
  We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min(-1). Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration.
  
  
  CONCLUSIONS
  In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.
authors.affiliation: Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands. p.g.j.ter.horst@isala.nl
authors.forename: Peter G J
authors.initials: PG
authors.lastname: ter Horst
authors.forename: Susanne
authors.initials: S
authors.lastname: van der Linde
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Smit
authors.forename: Jan
authors.initials: J
authors.lastname: den Boon
authors.forename: Richard A
authors.initials: RA
authors.lastname: van Lingen
authors.forename: Frank G A
authors.initials: FG
authors.lastname: Jansman
authors.forename: Lolkje T W
authors.initials: LT
authors.lastname: De Jong-van den Berg
authors.forename: Bob
authors.initials: B
authors.lastname: Wilffert
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D002997:Clomipramine / Q000009:adverse effects*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D009426:Netherlands; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine