Changes in antidepressant metabolism in pregnancy evidenced by metabolic ratios in hair: a novel approach.
BACKGROUND
Depression and other psychiatric illnesses are common during pregnancy and are often treated with antidepressants. Physiological changes of pregnancy may alter the pharmacokinetics of medications and ultimately affect the dose required to maintain effective therapy. Human hair offers a safe, non-invasive way to monitor long term systemic exposures to medications.


OBJECTIVE
To determine whether the ratio of hair antidepressant: major metabolite differed when early and late pregnancy was compared to the postpartum period.


METHODS
Segmental analyses using liquid chromatography-mass spectrometry-mass spectrometry were performed on hair samples. The mean concentration of parent compound and metabolite was found for each trimester and the postpartum period.


RESULTS
Twelve women provided hair samples of which nine samples were long enough to analyze the first and third trimesters along with the postpartum period. Citalopram, venlafaxine, fluoxetine and sertraline were the antidepressants studied. In the citalopram group, a statistically significant difference existed between the citalopram:norcitalopram ratio when the first trimester was compared to the postpartum period (0.89+/-0.26 versus 1.4+/-0.24 respectively, p=0.022). A statistically significant difference also existed between the third trimester and the postpartum period for the citalopram group (0.9+/-0.14 and 1.4+/-0.24 respectively, p=0.048). No other statistically significant differences were found.


CONCLUSIONS
It is important that variations in drug metabolism during pregnancy be considered as these changes may necessitate a dosage adjustment to ensure that therapeutic failure does not occur during pregnancy.
O'Brien
Lisa
L
Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada. lobrien14@gmail.com
Baumer
Carina
C
Thieme
Detlef
D
Sachs
Hans
H
Koren
Gideon
G
D000328:Adult; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D015283:Citalopram / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003511:Cyclohexanols / Q000493:pharmacokinetics; D005260:Female; D005473:Fluoxetine / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000378:metabolism*; D006801:Humans; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D020280:Sertraline / Q000493:pharmacokinetics; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D003511:Cyclohexanols; D005473:Fluoxetine; D015283:Citalopram; C046304:desmethylcitalopram; D000069470:Venlafaxine Hydrochloride; D020280:Sertraline