UBC Faculty Research and Publications

Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women… Hanley, Gillian E; Mintzes, Barbara Jul 22, 2014

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata


52383-12884_2014_Article_1118.pdf [ 497.33kB ]
JSON: 52383-1.0223616.json
JSON-LD: 52383-1.0223616-ld.json
RDF/XML (Pretty): 52383-1.0223616-rdf.xml
RDF/JSON: 52383-1.0223616-rdf.json
Turtle: 52383-1.0223616-turtle.txt
N-Triples: 52383-1.0223616-rdf-ntriples.txt
Original Record: 52383-1.0223616-source.json
Full Text

Full Text

RESEARCH ARTICLE Open AccessPatterns of psychotropic medicine use inpregnancy in the United States from 2006 topregnancy.Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242http://www.biomedcentral.com/1471-2393/14/242Sciences Mall, Vancouver, BC V6T 1Z3, CanadaFull list of author information is available at the end of the articleKeywords: Pregnancy, Prescription drugs, Psychiatric conditions in pregnancy, Psychotropic medicines,Administrative data, Depression, Anxiety* Correspondence: Barbara.mintzes@ti.ubc.ca1School of Population and Public Health, University of British Columbia,Vancouver, BC, Canada3Therapeutics Initiative, University of British Columbia, #307, 2176 Health2011 among women with private insuranceGillian E Hanley1,2 and Barbara Mintzes1,3*AbstractBackground: Psychiatric disorders are equally common during pregnancy as among non-pregnant women, andmany of these conditions are treated with psychotropic medicines. Relatively little is known about patterns of useof many these agents during pregnancy, and specifically of how rates may have shifted during the last decade. Weaimed to quantify the rate of pregnancy related exposures to categories of psychotropic medicines stratified accordingto the primary indication for use (antidepressants, antipsychotics, anxiolytics, and psychostimulants), trimester ofpregnancy, trends over time and region, and indication for use.Methods: We conducted a retrospective cohort study of pregnancies among women in the Truven Health MarketScandatabase (source population 70 million Americans), which captures person-specific clinical use and includes detailedinformation on filled prescriptions, hospitalizations and outpatient visits for all privately insured employees and theirdependents. We classified psychotropic medicines of interest using ATC level 3 accordingly: antipsychotics (N05A);anxiolytics (N05B); antidepressants (N06A); psychostimulants, agents used for ADHD and cognitive enhancement(N06B). We also examined temporal and regional trends in use.Results: We included 343,299 women who had a live birth between Jan 1, 2006 and Dec 31, 2011, of whom 10.3%were dispensed one or more psychotropic medicines during pregnancy. This rate varied from 6% to 15% betweenstates. The rate of use of psychotropic medicines was relatively stable between 2006 and 2011. The mostcommonly used psychotropic medicines were selective serotonin reuptake inhibitors (5.1%) and benzodiazepineor benzodiazepine-like medicines (3.9%). Among psychotropic users, the most commonly associated psychiatricdiagnosis was depression (25.0%), followed by anxiety disorders (24.4%). Approximately 1.6% of women usedmore than one category of psychotropic medicine in pregnancy, most commonly an antidepressant and ananxiolytic medicine (1.2%).Conclusions: Given this relatively high rate of use, the lack of evidence that the most frequently used medicationsimprove birth outcomes and the safety concerns associated with both early and late pregnancy use for manyfrequently-used medications, there is a need for further study of factors driving psychotropic medication use during© 2014 Hanley and Mintzes; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of theCreative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons PublicDomain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in thisarticle, unless otherwise stated.Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 2 of 12http://www.biomedcentral.com/1471-2393/14/242BackgroundIn North America, there is evidence that use of psy-chotropic medicines during pregnancy, especially anti-depressants, became increasingly prevalent in the early2000’s [1]. Pregnancy was historically considered protectiveagainst mental health disturbances. More recent commen-taries highlight pregnancy as a high-risk period [2]. Neitherappears to be the case, with the most reliable estimatessuggesting no significant difference in the rates of themost commonly diagnosed psychiatric disorders betweenpregnant and non-pregnant women of childbearing age,after adjustment for ethnicity, social class, age, health sta-tus and stressful life events [3-5]. The principal psychiatricdisorders encountered during pregnancy include majordepressive disorder, anxiety disorders, bipolar affectivedisorder, and schizophrenia [6]. These conditions areoften treated with psychotropic medicines, and little isknown about patterns of use of many these agents duringpregnancy, and specifically of how rates may have shiftedduring the last decade.While patterns of use during pregnancy of some cat-egories of psychotropic medicines, most notably selectiveserotonin reuptake inhibitor (SSRI) antidepressants, havebeen well studied, estimates of the rate of use vary widely.For example, studies from the Nordic countries have re-ported that fewer than 2% of women use antidepressantsduring pregnancy [7], whereas one study in a Medicaidpopulation in Tennessee reported use in 13.4% of all preg-nancies [1]. Rates of use have also changed considerablyover time [8-10]. This suggests that both temporal andgeographic factors are important in understanding useof psychotropic medicines during pregnancy. Thesedifferences may reflect a range of factors, includingunderlying prevalence, rates of diagnosis and care seeking,and proportions with drug versus non-drug treatment.The way that psychotropic medicines are prescribed hasalso shifted over time. For example, use of antipsychoticshas increased, and the approved indications for anti-psychotic drugs have expanded beyond psychotic dis-orders to include bipolar, major depressive, and anxietydisorders [11]. Previous research also suggests that therate of antipsychotic use during pregnancy has beenincreasing [12]. ADHD is increasingly being diagnosedamong adults as well as children [13]. Diagnosis andtreatment of more than one mental health disorder at atime is not uncommon, and depression and anxiety disor-ders are often diagnosed as comorbid conditions [14-16].A common methodological limitation to all studiesexamining outcomes of prescription drug use during preg-nancy is confounding by the underlying indication for themedicine use and other systematic differences at baselineaffecting both treatment decisions and outcomes. This islikely to be especially important for women who havemultiple mental health disorders, as their outcomes maybe confounded by their comorbid condition, and they maybe exposed to more than one psychotropic medication.Thus, examining the use of one category of psychotropicmedicine during pregnancy is unlikely to present acomplete picture of the pharmacologic exposure of theinfant or the mental health of the pregnant woman.Risks to the infant may also be higher with exposure tomore than one class of psychotropic medicine. Oberlanderet al. found higher risks of congenital heart defects amonginfants whose mothers were using both SSRI antidepres-sants and benzodiazepines during pregnancy [9]. Thus,understanding the complete picture of exposures to psy-chotropic medicines during pregnancy is important.In this study we aim to quantify the rate of pregnancyrelated exposures to categories of psychotropic medicinesstratified according to the primary indication for use(antidepressants, antipsychotics, anxiolytics, and psychos-timulants), trimester of pregnancy, trends over time andregion, and indication for use. We are especially interestedin the proportion of women using different classes ofdrugs who initiate use during pregnancy, versus ongoingexposures among established users. We also examined theuse of medicines from more than one category duringpregnancy (e.g. an antidepressant and an anxiolytic). De-fining how commonly psychotropic medicines are usedduring pregnancy, which psychotropic medicines are mostoften prescribed, what conditions are most commonlytreated with psychotropic medicines, and how psychotropicconditions are managed during pregnancy will help definenew research priorities in this field.MethodsWe conducted a retrospective cohort study of pregnanciesamong women in the Truven Health MarketScan database(source population 70 million), which captures person-specific clinical use and includes detailed information onfilled prescriptions, hospitalizations and outpatient visitsfor all insured employees and their dependents. Thesedata come from a selection of large employers, healthplans and government and public organizations (ap-proximately 100 payers) across multiple states in theUnited States. Ethics approval was obtained from theBehavioral Research Ethics Board at the University ofBritish Columbia.Study cohortWe included data from the first pregnancy for eachmother that ended in a live birth in hospital between Jan1, 2006 and Dec 31, 2011. Our data set includes primipar-ous and multiparous women, the latter with live birthsprior to 2006. Pregnancies were captured in the inpatientand outpatient data using ICD-9 diagnostic codes indicat-ing delivery in the maternal hospital record and outpatientrecord. To ensure complete capture of prescription drugsHanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 3 of 12http://www.biomedcentral.com/1471-2393/14/242used before and during pregnancy, we only includedwomen who were enrolled continually during preg-nancy and the three months pre-conception with nomore than a one-month gap in their health insuranceenrollment. As gestational age varied, the total numberof months in which the women needed to be enrolledin the health insurance plan varied with it.Definitions of pregnancy periodsMaternal hospital records provided the date of admissionfor each in-hospital birth, but not the date of birth. We as-sumed that the date of admission was equal to the deliverydate. The pregnancy period was built using the algorithmdeveloped by Li et al., which was shown to correctlyclassify medication exposure status in most live borndeliveries with a sensitivity and positive predictive valueof ≥95% and a specificity and negative predictive valueof almost 100% [17]. Using the gestational age (in days)calculated from the algorithm we estimated a date ofconception by subtracting gestational days from the ad-mission date. From this estimated conception date, webuilt several time periods for analysis of psychotropic drugexposures: 1) weeks 1 to 13 of gestation (first trimester);2) Weeks 14 to 26 of gestation (second trimester), 3) week27 of gestation to delivery (third trimester), 4) 6 monthsprior to conception (preconception) and, 5) six monthspostpartum (postpartum).Psychotropic drug use in pregnancyOutpatient prescription drug claims include prescriptionsdispensed to women at eligible pharmacies either througha mail-order or card program prescription drug claim,capturing all prescriptions dispensed that are covered byher insurance plan. We classified psychotropic medicinesof interest using ATC level 3 accordingly: antipsychotics(N05A); anxiolytics (N05B); antidepressants (N06A);psychostimulants, agents used for ADHD and cognitiveenhancement (N06B). Additional file 1 outlines all med-icines in each category that were dispensed to a womanin our cohort during pregnancy. We excluded the caf-feine and caffeine combinations that were included inN06B. We did not remove medicines that we suspectedwere being prescribed for non-psychological indications,such as the typical antipsychotics that appear to be usedprimarily as antiemetics, as these prescriptions still repre-sent exposures to a psychotropic medicine from one ofthe relevant drug classes. We also present frequencies ofwomen who filled prescriptions from more than 2 cat-egories of psychotropic medicines during the perinatalperiod, and the use of 2 or more different antidepressantmedicines during the perinatal period.We defined exposure to a psychotropic medicine duringpregnancy and according to trimester if a prescription wasfilled on a date within the relevant pregnancy period. Toaccount for the possible overestimation that might resultfrom including psychotropic medicines filled only once inthe first trimester, we also present conservative numbersof exposures during pregnancy where we have removedwomen who filled only 1 prescription during the first tri-mester of pregnancy, as these might represent prescrip-tions filled prior to knowledge of the pregnancy and notused once the woman became aware she was pregnant.Patterns of prescription drug exposureWe defined prevalent users of psychotropics duringpregnancy as women for whom the psychotropic wasdispensed in the 6 months prior to pregnancy and thenagain in pregnancy. In contrast, incident users werethose with no prescription for the psychotropic in the6-months before pregnancy. Again we also presentconservative estimates by removing the women whoonly filled one prescription for the psychotropic of interestin the first trimester from both groups. Finally we presentincident use of psychotropic medicines in the postpartumperiod, defined as initiation of use during the 180 daysfollowing delivery. These women had no prescription forthe psychotropic agent before or during pregnancy.Description of associated conditionsMedical conditions associated with use of psychotropicswere identified using the International Classification ofDiseases, Ninth Revision diagnosis codes in the patient’shospital and outpatient records between 180 days beforeour estimated conception date and delivery. Additionalfile 2: Table S1 outlines the diagnostic codes used. Thefrequency of these conditions was determined in (1) allpatients exposed to psychotropics agents during pregnancy(2) patients exposed to each category of psychotropicmedicine (3) according to incident or prevalent use of psy-chotropic medicines and for the two most commonly usedcategories of psychotropic medicines, antidepressants andanxiolytics and (4) among women who did not fill pre-scriptions for psychotropic medicines in pregnancy.Temporal and regional trends in psychotropic medicineuse during pregnancyWe examined the trends in exposure to any psychotropicmedicine during pregnancy and to each category of psycho-tropic medicines annually from 2007 to 2011 according tothe year of delivery. We examined regional variationsin psychotropic prescribing by examining frequency ofexposure to psychotropic medicines, antidepressantsand anxiolytics by state.Statistical analysesAll analyses were descriptive of this commercially insuredpopulation. The results are parameters for this particularpopulation rather than estimates based on a sample andthus we present the results without confidence intervals. Allanalyses were performed using either Stata version 13.0 (Col-lege Station, TX) or SAS version 9.3 (SAS Institute, Cary, NC).ResultsThere were 343,299 live births between Jan 1, 2006 andDec 31, 2011 that met our enrollment criteria (not missingmore than one month of enrollment for the 3 monthsprior to conception and during the pregnancy). The meanage of the women at the time of delivery was 30.3 yearswith a standard deviation of 5.6 years (median 30 andinterquartile range 27 to 34); 4,895 (1.4%) pregnancieswere multiple gestations, 29,733 (8.7%) were pretermdeliveries. Overall 35,303 women (10.3%) were prescribeda psychotropic medicine during pregnancy (this numberdrops to 6.8% when we remove women who only filledone prescription during the first trimester of pregnancy).24,776 (7.2%) women filled a prescription for a psycho-tropic medicine during the first trimester, 15,883 (4.6%)during the second trimester and 18,161 (5.3%) during thethird trimester. The most common category of psychotropicmedicine use during pregnancy was antidepressants, withthan one category of psychotropic medicine during preg-nancy, and most of these women were using a combin-ation of antidepressants and anxiolytics (4,068, 1.2%).Patterns of prescription drug exposureRates of use of all psychotropic medicines were higher inthe 6 months preconception than in the first trimesterand decreased further in the second trimester, likelyreflecting women who stopped medicines after becomingaware of their pregnancy. This pattern was consistentacross all categories of psychotropic medicine except fortypical antipsychotics, which were used considerably morein the first trimester of pregnancy, likely as an antiemetic.The most common class of antidepressants dispensedduring pregnancy were SSRIs which were dispensed to17,410 (5.1%) of women followed by selective norepin-ephrine reuptake inhibitors (dispensed to 2,382 or 0.8%of women). Table 2 lists the most common psychotropicmedicines among each category and includes all medicinesthat were used by at least 0.1% of the study population.Among SSRIs the most commonly dispensed medicineswere sertraline, fluoxetine, and escitalopram with 8,432ugste)))Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 4 of 12http://www.biomedcentral.com/1471-2393/14/24222,275 (6.5%) women filling an antidepressant during preg-nancy (conservative estimates are 15,097 (4.4%)), followedby anxiolytics which were filled by 14,535 (4.2%) of pregnantwomen in our cohort (conservatives estimates are 9,235(2.7%)). Antipsychotics and stimulants were used duringpregnancy by 2,373 (1.1%) and 2,062 (0.6%) respectively(Table 1). There were 5,423 (1.6%) women using moreTable 1 Summary measures of psychotropic prescription drN = 343299 6 months preconceptn (%)1st trimen (%)Any psychotropic 33,995 (9.9) 24776 (7.2Antidepressant 23,083 (6.7) 17214 (5.0SSRI 16524 (4.8) 12881 (3.8SNRI 3170 (0.9) 2175 (0.6)Tricyclic 1222 (0.4) 611 (0.2)Other 4390 (1.3) 3085 (0.9)≥ 2 antidepressants 2776 (0.8) 2132 (0.6)Anxiolytic 12969 (3.8) 7503 (2.2)Benzo or benzo-like* 12231 (3.5) 6840 (2.0)Other 950 (0.3) 809 (0.2)Antipsychotic 1344 (0.4) 1728 (0.5)Atypical 899 (0.3) 604 (0.2)Typical 357 (0.1) 1072 (0.3)Stimulant/ADHD 2798 (0.8) 1982 (0.6)≥ 2 categories of psychotropic** 5423 (1.6) 3339 (1.0)Antidepressant + anxiolytic 4195 (1.2) 2293 (0.7)*Includes benzodiazepines as well as eszopliclone, zolpiedem, and zaleplon.**defined as prescriptions for ≥ 1 class of psychotropic medicine during pregnancyused ≥ 1 medicine within the same class (e.g. two antidepressants).(2.5%), 3,605 (1.1%), and 3,481 (1.0%) of women fillinga prescription for these medicines during pregnancyrespectively. Nearly all of the anxiolytics prescribedwere benzodiazepines or benzodiazepine-like medicines(n = 13,486, 3.9%), the latter including zaleplon, zolpidem,and eszopiclone. The most common benzodiazepine orbenzodiazepine-like medicines prescribed were zolpidemuse before, during and after pregnancyr 2nd trimestern (%)3rd trimestern (%)Pregnancytotal n (%)Pregnancy totalwith >1 Rx n (%)15883 (4.6) 18161 (5.3) 35303 (10.3) 23261 (6.8)12235 (3.6) 11937 (3.5) 22275 (6.5) 15097 (4.4)9773 (2.9) 9751 (2.8) 17410 (5.1) 12278 (3.6)973 (0.3) 805 (0.2) 2382 (0.8) 1075 (0.3)236 (0.07) 209 (0.06) 784 (0.2) 308 (0.1)1875 (0.6) 1634 (0.5) 4019 (1.2) 1026 (0.3)889 (0.3) 676 (0.2) 3521 (1.0) 1613 (0.5)3881 (1.1) 7002 (2.0) 14535 (4.2) 9235 (2.7)3391 (1.0) 6686 (2.0) 13486 (3.9) 8613 (2.5)549 (0.2) 377 (0.1) 1375 (0.4) 757 (0.2)808 (0.2) 503 (0.1) 2373 (1.1) 1015 (0.3)315 (0.1) 301 (0.1) 742 (0.2) 388 (0.1)464 (0.1) 160 (0.05) 1573 (0.5) 995 (0.3)498 (0.1) 325 (0.1) 2062 (0.6) 545 (0.2)1431 (0.4) 1519 (0.5) 5423 (1.6) 2390 (0.7)1064 (0.3) 1247 (0.36) 4068 (1.2) 1630 (0.5)e.g. a benzodiazepine and an antidepressant; does not include women whotivCd16222971Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 5 of 12http://www.biomedcentral.com/1471-2393/14/242Table 2 Most common psychotropic exposures (not exhausby ≥ 0.1% of the study population)Drug class Number exposedduring pregnancySSRI 17414 (5.1)Sertraline 8432 (2.5)Fluoxetine 3605 (1.1)Escitalopram 3481 (1.0)Citalopram 2295 (0.7)Benzodiazepines (and benzo like) 13486 (3.9)Zolpidem 8239 (2.4)Alprazolam 2654 (0.8)(n = 8,239, 2.4%), alprazolam (n = 2,654, 0.8%), diazepam(n = 1,884, 0.6%) and lorazepam (n = 1,233, 0.4%).The majority of typical antipsychotic prescriptionsduring pregnancy were for prochloperazine (n = 1527,0.4%), and nearly half of these prescriptions occurredonly during the first trimester. The conservative numberof women exposed, excluding women with a single pre-scription in the first trimester, drops to 682 (0.2%). Ifprochloperazine was primarily being used as an anti-emetic, women may have filled a single prescription forshort-term relief of first trimester nausea. As we couldnot distinguish between this situation and women whodiscontinued drug use when they knew they were pregnant,we retained the same definition of conservative use as withother medications. Only 17% of women with prescriptionsDiazepam 1884 (0.6) 3Lorazepam 1233 (0.4) 6Other antidepressants 4019 (1.2) 2Bupropion 3399 (1.0) 2Trazodone 602 (0.2) 2SNRIs 2382 (0.7) 1Venlafaxine 1398 (0.4) 9Duloxetine 795 (0.2) 4Desvenlafaxine 210 (0.1) 1Typical antipsychotics 1573 (0.5) 7Prochlorperazine 1527 (0.4) 6Other anxiolytics 1375 (0.4) 8Buspirone 745 (0.2) 5Scopolamine 535 (0.2) 2Amphetamine 1291 (0.4) 6Cyclic antidepressants 784 (0.2) 3Amitriptyline 490 (0.1) 2Nortriptyline 173 (0.1) 7Atypical antipsychotics 742 (0.2) 4Quetiapine 363 (0.1) 2*Removes women who only filled one prescription in the first trimester.e of all drug exposures—only medicines that were usedonservative number exposeduring pregnancy*Number who filled morethan 1 Rx during pregnancy3379 (3.9) 11142 (3.3)936 (2.0) 5360 (1.6)694 (0.8) 2300 (0.7)310 (0.7) 1951 (0.6)310 (0.7) 1246 (0.4)399 (2.7) 4304 (1.3)238 (2.1) 2676 (0.8)288 (0.4) 893 (0.3)for typical antipsychotics during pregnancy refilled theirprescription (n = 274, 0.1%). The most commonly usedatypical antipsychotic was quetiapine, which has been ap-proved to treat major depressive disorder. However, use ofquetiapine in pregnancy was uncommon (n = 363, 0.1%).Table 3 shows the mean, median and interquartilerange for the cumulative numbers of days supply duringthe pregnancy among the patients dispensed each categoryof psychotropic medicine. The median duration of anti-depressant use during pregnancy was 90 days with a meanduration of 125.3 days, reflecting exposure for nearly halfthe pregnancy. This duration of exposure was similaramong women using SSRIs and slightly shorter amongwomen using SNRIs (median 60 days, mean 111.1) andother antidepressants (median 60 days, mean 100.0 days).84 (0.1) 178 (0.05)34 (0.2) 302 (0.1)658 (0.8) 2164 (0.6)351 (0.7) 1925 (0.6)70 (0.1) 189 (0.1)474 (0.4) 1377 (0.4)36 (0.3) 875 (0.3)49 (0.1) 416 (0.1)00 (0.03) 96 (0.03)12 (0.2) 274 (0.1)82 (0.2) 250 (0.1)20 (0.2) 375 (0.1)20 (0.2) 288 (0.1)48 (0.1) 56 (0.02)57 (0.2) 633 (0.2)85 (0.1) 272 (0.1)39 (0.1) 162 (0.05)5 (0.02) 56 (0.02)65 (0.1) 397 (0.1)28 (0.1) 191 (0.06)Table 3 For psychotropic medicines dispensed during pregnancy, number of days exposure during pregnancy by typeMedian 25th percentile 75th percentile Mean ± SDAny psychotropic 60 30 160 104 ± 118.2Antidepressant 90 30 210 125.3 ± 103.2SSRI 90 30 180 118.9 ± 91.4SNRI 60 30 180 111.1 ± 98.6Cyclic 30 30 80 69.1 ± 72.5Other 60 30 150 100.0 ± 90.3Anxiolytic 30 10 40 43.2 ± 65.6Benzo or benzo-like 29 10 40 41.8 ± 64.0Other 30 12 40 46.7 ± 59.7Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 6 of 12http://www.biomedcentral.com/1471-2393/14/242Anxiolytic exposure was much shorter with a median ex-posure of 30 days and a mean of 43.2 days. The shortestduration of exposure was among the typical antipsychotics,including prochlorperazine (97% of use in this class),amitriptyline, chlorpromazine, fluphenazine, haloperidol,loxapine, perphenazine, thioridazine, and trifluoperazine.Typical antipsychotics were used for a median of 8 daysand a mean of 14.7 days. Stimulants had median exposureduration of 49 days (mean 79.8).Table 4 outlines psychotropic medicine use duringpregnancy according to whether the use represents preva-lent or incident use in pregnancy. Most use of antide-pressants during pregnancy represents prevalent use(n = 15,253, 4.4%; Table 4). In contrast, anxiolytics (primar-Antipsychotic 14 7Atypical 60 30Typical 8 5Stimulant/ADHD 49 30ily benzodiazepines and benzodiazepine-like medicines)were most often initiated during pregnancy (n = 9,215, 2.7%incident users versus n = 4271, 1.2% prevalent users). Typ-ical antipsychotics were also used primarily by incidentusers in pregnancy (Table 4).Table 4 Prevalent and incident use of psychotropic medicinesN = 343,299 Prevalent usein pregnancyPrevalent use inpregnancy; > 1 Rx*Antidepressants 15253 (4.4) 11588 (3.4)SSRI 10998 (3.2) 8300 (2.4)Anxiolytics 4574 (1.3) 2992 (0.9)Benzo** 4271 (1.2) 2742 (0.8)Antipsychotic 559 (0.2) 365 (0.1)Typical antipsychotic 27 (0.01) 14 (0.00)Atypical antipsychotic 480 (0.1) 307 (0.09)ADHD 1741 (0.5) 886 (0.3)*Removes women who only filled one prescription in the first trimester.**benzodiazepine or benzodiazepine like product.Description of associated conditionsTable 5 shows the relevant mental health conditions inpatients with and without psychotropic medicine useduring pregnancy. Of the 35,303 psychotropic medicineusers during pregnancy, just under half had a relevantdiagnosis (49.7%) at any time during pregnancy or in thesix months pre-conception. Of these, the most commondiagnoses were depressive disorders (25.0%) and anxietydisorders (24.4%); 31.5% of antidepressant users had beendiagnosed with anxiety compared to 35.3% diagnosed witha depressive disorder. Just under half of all users of stimu-lants had a diagnosis of ADHD (49.6%) and 72.3% of allstimulant users had a diagnosis of at least one mentalhealth disorder. Women who were using more than one30 46.4 ± 81.7150 103.8 ± 102.515 14.7 ± 24.490 79.8 ± 89.9psychotropic during pregnancy were most likely to have atleast one relevant psychiatric diagnosis (73.9%). Therewere 11,181 women with a diagnosis of depression and14,102 women with a diagnosis of an anxiety disorderwho did not use psychotropic medicines during pregnancyduring the perinatal periodIncident use inpregnancyIncident use inpregnancy > 1 Rx*Incident usepostpartum7,022 (2.1) 5353 (1.6) 15652 (4.6)6,416 (1.9) 5079 (1.5) 14625 (4.3)9961 (2.9) 7100 (2.1) 7583 (2.2)9,215 (2.7) 6657 (1.9) 7319 (2.1)1814 (0.5) 854 (0.3) 773 (0.2)1546 (0.5) 698 (0.2) 326 (0.1)262 (0.1) 158 (0.05) 447 (0.1)321 (0.1) 135 (0.04) 604 (0.2)oiol14(4.4 (18 (21 (80.10.33 (7(2.6 (3Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 7 of 12http://www.biomedcentral.com/1471-2393/14/242representing 57% and 62% of women in our data set withthese diagnoses, respectively. Of the 11,217 women diag-nosed with acute stress or adjustment disorder, 3176(28%) were prescribed a psychotropic drug, most often anantidepressant.Table 6 shows diagnoses for mental health disordersaccording to prevalent and incident use of psychotropicmedicines, antidepressants and anxiolytics (as well asconservative prevalent and incident use). The rate of userswith a relevant diagnosis is nearly double for prevalentusers of psychotropic medicines compared with incidentusers (63.1% versus 31.1% respectively).Temporal and regional trendsFigure 1 shows psychotropic medicine use during preg-nancy across each year of study. The figure indicatesremarkable consistency in exposure to psychotropicmedicines during the study period. There was a slightTable 5 Diagnosed maternal conditions in the year prior topsychotropic medicinesDiagnoses, n (%) Any psychotropicN= 35303AntidepressantN= 22275AnxN=Bipolar disorder 1637 (4.6) 1225 (5.5) 581Major depressive disorder 8814 (25.0) 7874 (35.3) 241Anxiety 8611 (24.4) 7006 (31.5) 318Adj/Acute stress‡ 3176 (9.0) 2335 (10.5) 126Schizophrenia 48 (0.1) 28 (0.1) 11 (Personality disorder 143 (0.4) 116 (0.5) 40 (Sleep disorder 1799 (5.1) 1130 (5.1) 103ADHD 1347 (3.8) 546 (2.5) 292At least one relevant diagnosis 17561 (49.7) 13655 (61.3) 578‡A diagnosis of adjustment reaction and/or acute stress.decrease in antidepressant use between 2010 and 2011from 6.7% to 6.4%, and the use of stimulants increasedfrom 0.4% in 2007 to 0.9% in 2011. Figure 2 shows therate of psychotropic exposure during pregnancy bystate. Significant regional differences are observed withthe lowest rates of psychotropic use being observed inNew York (6.44%) and California (6.99%) and the highestrates of use in Idaho (15.41%), Louisiana (14.94%), Utah(14.80%), West Virginia (14.44%), and South Carolina(14.17%). A number of the Southern states had higherthan average rates, with Alabama, Arkansas, Kentucky,Louisiana, North and South Carolina, Indiana, Tennesseeand West Virginia all having rates above 12%.DiscussionIn this analysis of nearly 350,000 pregnancies amongwomen with private health insurance from across theUnited States, we found that at least one psychotropicmedicine was dispensed to 1 in 10 pregnant womenduring pregnancy. The most commonly used medicinesduring pregnancy were antidepressants (selective serotoninreuptake inhibitors specifically) and anxiolytics (benzodi-azepine and benzodiazepine-like medicines). We also reportthat 1.6% of women were using two or more different cat-egories of psychotropic medicines during pregnancy, mostoften an antidepressant and an anxiolytic. The medianduration of exposure was 60 days, ranging from 29 to90 days for all categories of medications except for typicalantipsychotics, which are often used as antiemetics. Rela-tively few women received atypical antipsychotics (1.1%)or stimulants or other drugs for ADHD (0.6%). We foundvery little variation in the rate of exposure over the studyperiod, with approximately 10% of pregnant women usinga psychotropic medicine during pregnancy in each yearbetween 2007 and 2011.The most common psychiatric diagnoses in this cohortin the period from six months pre-pregnancy to the endr during pregnancy, stratified by exposure toytic535Stimulants forADHD N=2062AntipsychoticN = 2373No psycho-tropicuse N= 307996More thanone N= 54230) 499 (24.2) 98 (4.1) 1747 (0.6) 634 (11.7)6.6) 488 (23.7) 218 (9.2) 11861 (3.9) 2036 (37.5)1.9) 487 (23.6) 213 (9.0) 14102 (4.6) 2127 (39.2).7) 179 (8.7) 211 (8.9) 8041 (2.6) 725 (13.4)) 35 (1.7) 1 (0.04) 34 (0.01) 22 (0.4)) 27 (1.3) 3 (0.1) 141 (0.05) 38 (0.7).1) 75 (3.6) 34 (1.4) 3255 (1.1) 472 (8.7)0) 1023 (49.6) 73 (3.1) 1119 (0.4) 469 (8.6)9.8) 1490 (72.3) 1086 (45.8) 25707 (8.3) 4007 (73.9)of pregnancy was anxiety (n = 22,713) followed by depres-sion (n = 20,675), with 37.9% and 42.6% of those with eachdiagnosis, respectively, receiving psychotropic medicationsin pregnancy. The latter is similar to the 40.3% rate ofantidepressant use among women with a relevant diagno-sis in a national US study of over one million pregnantlow-income women covered by Medicaid from 2000 to2007 [18]. Among women taking antidepressants, anxietydiagnoses (31.5%) were nearly as prevalent as depressiondiagnoses (35.3%), and there were twice as many antide-pressants users with an anxiety diagnosis than anxiolyticusers with an anxiety diagnosis (7,006 compared with3,176).What do these findings mean for maternal and infanthealth and well-being? While the evidence in this area iscomplex and often contradictory, and a full evidencereview is beyond the scope of this article, a few areas ofconcern merit discussion in order to provide necessarycontext for our results. Pregnant women with depressionTable 6 Diagnoses by prevalent and incident use of psychotropics, antidepressants and anxiolyticsPrevalent useduring pregnancyConservativeprevalent use*Incident usein pregnancyConservativeIncident use*Psychotropic users N = 20481 N = 15689 N = 14822 N = 10798Bipolar disorder 1294 (6.3) 1105 (7.0) 342 (2.3) 278 (2.6)MDD 6724 (32.8) 5680 (36.2) 2084 (14.1) 1730 (16.0)Anxiety 6450 (31.5) 5266 (33.6) 2153 (14.5) 1651 (15.3)Sleep disorder 1360 (6.6) 1076 (6.9) 439 (3.0) 319 (3.0)ADHD 1208 (5.9) 877 (5.6) 139 (1.0) 86 (0.8)Adj/acute‡ 2098 (10.2) 1652 (10.5) 1078 (7.3) 800 (7.4)Any relevant diagnosis 12921 (63.1) 10400 (66.3) 4640 (31.3) 3567 (33.0)Antidepressant users N = 15253 N = 11588 N = 7022 N = 5353Bipolar disorder 895 (5.9) 721 (6.2) 329 (4.7) 250 (4.7)MDD 5858 (38.4) 4789 (41.3) 2010 (28.6) 1629 (30.4)Anxiety 5176 (33.9) 4118 (35.5) 1822 (26.0) 1372 (25.6)Sleep disorder 844 (5.5) 637 (5.5) 286 (4.1) 210 (3.9)ADHD 402 (2.6) 315 (2.7) 144 (2.1) 104 (1.9)Adj/acute‡ 1623 (10.6) 1241 (10.7) 712 (10.1) 532 (9.9)Any relevant diagnosis 9967 (65.3) 7896 (68.1) 3688 (52.5) 2821 (52.7)Anxiolytic users N = 4574 N = 2993 N = 9961 N = 7099Bipolar disorder 325 (7.1) 240 (8.0) 255 (2.6) 181 (2.6)MDD 1181 (25.8) 826 (27.6) 1227 (12.3) 886 (12.5)Anxiety 1609 (35.2) 1075 (35.9) 1571 (15.8) 1016 (14.3)Sleep disorder 596 (13.0) 407 (13.6) 437 (4.4) 294 (4.1)ADHD 166 (3.6) 119 (4.0) 126 (1.3) 102 (1.4)Adj/acute‡ 506 (11.1) 332 (11.1) 755 (7.6) 524 (7.4)Any relevant diagnosis 2753 (60.2) 1858 (62.1) 3033 (30.5) 2080 (29.3)*Removes women who filled 1 prescription in the first trimester.‡A diagnosis of adjustment reaction and/or acute stress.Figure 1 Psychotropic medicine use during pregnancy by year.Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 8 of 12http://www.biomedcentral.com/1471-2393/14/242Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 9 of 12http://www.biomedcentral.com/1471-2393/14/242have worse birth outcomes, on average, than womenwithout a psychiatric diagnosis, and this is often used asa rationale to support drug treatment in pregnancy [19].However, the evidence on depression and pregnancyoutcomes has been criticized for inadequately addressingconfounding [20], including socio-economic factors[19,21], psychiatric diagnoses [22] and pregnancy com-plications [23,24], and it is often unclear whetherdepression and anxiety diagnoses precede or followpregnancy complications [25]. More importantly, todate there is no evidence that antidepressants fordepression or anxiolytics for anxiety mitigate poorerFigure 2 Psychotropic medicine use during pregnancy by state.health outcomes among women with depression oranxiety-related diagnoses [26-28]. The medicines usedto treat these mood disorders have been associatedwith poorer birth outcomes [29,30]. Selective serotoninuse in pregnancy has been associated with a number ofadverse health outcomes, including a higher rate ofmiscarriage [31], pre-term birth [32], congenital heartmalformations with first trimester exposure [33], andpersistent pulmonary hypertension of the newborn[34]. The extent to which poorer health outcomes withantidepressant exposure are a result of unmeasuredconfounding by the underlying maternal depression oranxiety remains an open question [9]. There is less incon-sistency with respect to postnatal adaptation syndrome, asyndrome that generally presents as a transient combin-ation of respiratory distress, jitteriness, abnormal tone,tremors, restlessness, convulsions, jaundice, rigidity, andhypoglycaemia [35-38], and occurs in approximately 1/3rdof newborns exposed to SSRIs in utero [39]. The evidenceon safety of use of atypical antipsychotics is sparse buttends to suggest an increased risk of NICU admissionamong exposed infants; however, the population ofantipsychotic users tends to have much higher rates ofmany adverse conditions, which likely confounds thisassociation [40,41]. There is some evidence from case–control studies of an increased risk of cleft palate withbenzodiazepine use in the first trimester [42], and aneonatal withdrawal syndrome following third trimesteruse [42,43]. A research study from Taiwan has suggestedthat zolpidem, the most frequently used anxiolytic inour cohort, is associated with poorer infant outcomes;however, unmeasured confounding is again a very realproblem in this literature [44].Our results were not consistent with earlier studiesreporting a trend of increased use of psychotropic medi-cines during pregnancy. Cooper et al. examined a publiclyinsured American Medicaid population in Tennessee andreported that antidepressant use more than doubled be-tween 1999 and 2003 from 5% to 13% [1]. A more recentnational study of women covered by Medicaid from 2000to 2007 found that 8.1% were dispensed antidepressants inpregnancy [18]. They also found that antidepressant usedeclined following an FDA warning in 2003 on increasedrisk for suicidality in children and adolescents [18]. Al-though largely irrelevant to use in pregnancy, this mayhave led to greater overall caution. The higher ratereported (8.1% versus our rate of 6.7%) may reflect greaterexposure among women of lower socio-economic status;however, there is only one year of overlap in the two ana-lyses, and although we found no difference in exposurerate from 2007 to 2011, an earlier shift in rate of drug usemay have occurred. Our results regarding higher rates ofuse of psychotropic medicines in Southern states is con-sistent with regional variation in depression diagnosesamong adults reported in US epidemiological surveys[45]. Our study also indicates higher than average rates inHanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 10 of 12http://www.biomedcentral.com/1471-2393/14/242some Mid-Western and Western states, a finding thatdiffers from disease surveillance surveys but should beinterpreted with caution, as we have some small num-bers in some of these states (e.g. Idaho n = 785; Kansasn = 2,833)We found little use of atypical antipsychotics (0.2%).Other research has reported an increasing trend in off-label use of antipsychotics in the general US population,including, for example, prescribing of quetiapine forinsomnia [11]. While we reported a high rate of use oftypical antipsychotics in the first trimester, given themedian prescription length (8 days) and frequent incidentuse in the first trimester, we expect that this representsuse as antiemetics. Prochlorperazine, the most commonlyprescribed typical antipsychotic in our cohort, is indicatedin the U.S. for severe nausea and vomiting. However, thedrug’s label warns against use in pregnancy, “except incases of severe nausea and vomiting that are so seriousand intractable that, in the judgment of the physician,drug intervention is required and potential benefits out-weigh possible hazards” [46].Our study is subject to some limitations. Our data aredrawn from a large private insurance claims databasethat includes women from across the United States (44states are represented). However, a large proportion ofbirths in the US occur to women who are covered byMedicaid [47], and it is unclear whether our findingsgeneralize to these women. The same applies to ourstate-specific prescribing patterns, which only reflectprescribing patterns of this commercially insured popu-lation. However, the general regional trends we presentare consistent with previous studies of prescription druguse during pregnancy [1,48]. We were also unable toidentify pregnancies that ended in spontaneous abortions,or therapeutic abortions, a population which may havehigher exposure to psychotropic medicines [31]. Any biascreated through these omissions is likely to be in the dir-ection of underestimating exposure.Our measure of exposure is based on pharmacy dis-pensing of medication, and does not directly measuremedication use by the pregnant women. To accountfor this limitation, we provide conservative estimates thatremove women who filled only one prescription in thefirst trimester, as these women seem most likely tohave filled prescriptions that might not have been used.Finally, we had to impute last menstrual period based onclaims for labor and delivery, which provide informationon preterm birth. Although this approach has been shownto be valid [17], some degree of misclassification is likely.We are also limited in our ability to detect diagnosedmental health conditions. While ICD-9 codes are helpfulin identifying conditions, they do not reflect a gold-standard diagnosis and a preferable measure would be adiagnostic interview undertaken by a trained health careprovider. We also report that only half of our psychotropicmedicine users had a relevant mental health diagnosis.While this may reflect some missing diagnostic informa-tion due to one-month lapses in coverage, it is also con-sistent with results from the US National AmbulatoryMedical care surveys indicating the lack of psychiatricdiagnosis noted at two-thirds of primary care consulta-tions at which an antidepressant was prescribed [49].The fact that many of these medicines are commonlyprescribed for other indications may also be a relevantfactor, as our rates of diagnoses were higher amongwomen using categories of medicines with less off-labeluse (e.g. stimulants to treat ADHD).ConclusionsIn summary, approximately 10% of privately-insuredwomen in the United States are dispensed one or morepsychotropic medicine during pregnancy, with importantregional variation, around 6% to 15%. The most commonlyused psychotropic medicines are selective serotonin re-uptake inhibitors and benzodiazepine or benzodiazepine-like medicines. The most commonly associated psychiatricdiagnosis was depression, followed by anxiety disorders,which were mainly treated with antidepressants. Approxi-mately 1.2% of women use both an antidepressant and ananxiolytic medicine during their pregnancy. Given theserelatively high rates of use, the lack of evidence that themost frequently used medications improve birth outcomes,and the safety concerns raised both by early and late preg-nancy use for many frequently-used medications, there isa need for further study of factors driving use of thesemedicines during pregnancy. For depression and anxietydisorders, alternative treatment options are available. Onequestion raised by these findings is the extent to whichpregnant women, and women of reproductive age whomay be planning pregnancy, have equivalent access tonon-drug as to drug options for common mental healthconcerns.Additional filesAdditional file 1: Generic names of all psychotropic medicinesprescribed during pregnancy to women in our cohort.Additional file 2: Table S1. Mental health ICD-9 codes.Competing interestsThe authors declare they have no competing interests.Authors’ contributionsGEH participated in devising the analytical plan, carried our data analysis anddrafted the manuscript. BM participated in devising the analytical plan, andedited the draft. Both authors read and approved the final manuscript.AcknowledgmentsWe would like to thank Dr. Anat Fisher for her help with data cleaning andpreparation and Mr. Greg Carney and Dr. Colin Dormuth for their help withdata acquisition. Dr. Fisher and Mr. Carney are funded by the University ofhealth data. Arch Gen Psychiatry 2006, 63(8):898–906.Hanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 11 of 12http://www.biomedcentral.com/1471-2393/14/24210. Daw JR, Mintzes B, Law MR, Hanley GE, Morgan SG: Prescription drug usein pregnancy: a retrospective, population-based study in BritishColumbia, Canada (2001–2006). Clin Ther 2011, 34(1):239–249.11. Alexander GC, Gallagher SA, Mascola A, Moloney RM, Stafford RS: Increasingoff-label use of antipsychotic medications in the United States,1995–2008. Pharmacoepidemiol Drug Safety 2011, 20(2):177–184.12. McKenna K, Einarson A, Levinson A, Koren G: Significant changes inantipsychotic drug use during pregnancy. Vet Hum Toxicol 2004,46(1):44–46.13. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, FaraoneSV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE,Zaslavsky AM: The prevalence and correlates of adult ADHD in theUnited States: results from the National Comorbidity Survey Replication.Am J Psychiatry 2006, 163(4):716–723.14. Figueiredo B, Conde A: Anxiety and depression in women and men fromearly pregnancy to 3-months postpartum. Arch Women's Mental Health2011, 14(3):247–255.15. Grigoriadis S, De CM, Barrons E, Bradley L, Eady A, Fishell A, Mamisachvili L,Victoria Centre on Aging, and Dr. Carney and Dr. Dormuth by the DrugSafety and Effectiveness CNODES network. We would also like toacknowledge our funders. G. Hanley is supported by the Canadian Institutesfor Health Research, the Michael Smith Foundation for Health Research,Women’s Health Research Institute and Neurodevnet. B. Mintzes holds aMichael Smith Health Research Foundation Scholar Award. This study wassupported by the Canadian Institutes of Health Research [Grant # 263768].The funders were not involved in any part of the study.Author details1School of Population and Public Health, University of British Columbia,Vancouver, BC, Canada. 2Child & Family Research Institute, Vancouver, BC,Canada. 3Therapeutics Initiative, University of British Columbia, #307, 2176Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.Received: 24 April 2014 Accepted: 8 July 2014Published: 22 July 2014References1. Cooper WO, Willy ME, Pont SJ, Ray WA: Increasing use of antidepressantsin pregnancy. Am J Obstet Gynecol 2007, 196(6):544e1–544e5.2. Muzik M, Marcus SM, Heringhausen JE, Flynn H: When depressioncomplicates childbearing: guidelines for screening and treatment duringantenatal and postpartum obstetric care. Obstet Gynecol Clin North Am2009, 36(4):771–788.3. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T:Perinatal depression: a systematic review of prevalence and incidence.Obstet Gynecol 2005, 106(5):1071–1083.4. Gaynes BN, Gavin N, Meltzer-Brody S, Lohr KN, Swinson T, Gartlehner G,Brody S, Miller WC: Perinatal Depression: Prevalence, Screening Accuracy, andScreening Outcomes: Summary. 2005.5. Vesga-Lopez O, Blanco C, Keyes K, Olfson M, Grant BF, Hasin DS: Psychiatricdisorders in pregnant and postpartum women in the United States. ArchGen Psychiatry 2008, 65(7):805–815.6. Oyebode F, Rastogi A, Berrisford G, Coccia F: Psychotropics in pregnancy:safety and other considerations. Pharmacol Ther 2012, 135(1):71–77.7. Kieler H, Artama M, Engeland A, Ericsson O, Furu K, Gissler M, Nielsen RB,Norgaard M, Stephansson O, Valdimarsdottir U, Zoega H, Haglund B:Selective serotonin reuptake inhibitors during pregnancy and risk ofpersistent pulmonary hypertension in the newborn: population basedcohort study from the five Nordic countries. BMJ 2012, 344:d8012.8. Petersen I, Gilbert RE, Evans SJ, Man SL, Nazareth I: Pregnancy as a majordeterminant for discontinuation of antidepressants: an analysis of datafrom The Health Improvement Network. J Clin Psychiatry 2011,72(7):979–985.9. Oberlander TF, Warburton W, Misri S, Aghajanian J, Hertzman C: Neonataloutcomes after prenatal exposure to selective serotonin reuptake inhibitorantidepressants and maternal depression using population-based linkedCook GS, O'Keefe M, Romans S, Ross LE: Mood and anxiety disorders in asample of Canadian perinatal women referred for psychiatric care. ArchWomen's Mental Health 2011, 14(4):325–333.16. Swanson LM, Pickett SM, Flynn H, Armitage R: Relationships amongdepression, anxiety, and insomnia symptoms in perinatal womenseeking mental health treatment. J Women's Health 2011, 20(4):553–558.17. Li Q, Andrade SE, Cooper WO, Davis RL, Dublin S, Hammad TA, Pawloski PA,Pinheiro SP, Raebel MA, Scott PE, Smith DH, Dashevsky I, Haffenreffer K,Johnson KE, Toh S: Validation of an algorithm to estimate gestational agein electronic health plan databases. Pharmacoepidemiol Drug Saf 2013,22(5):524–532.18. Huybrechts KF, Palmsten K, Mogun H, Kowal M, Avorn J, Setoguchi-Iwata S,Hernandez-Diaz S: National trends in antidepressant medication treatmentamong publicly insured pregnant women. Gen Hosp Psychiatry 2013,35(3):265–271.19. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ: Ameta-analysis of depression during pregnancy and the risk of pretermbirth, low birth weight, and intrauterine growth restriction. Arch GenPsychiatry 2010, 67(10):1012–1024.20. Alder J, Fink N, Bitzer J, Hösli I, Holzgreve W: Depression and anxietyduring pregnancy: A risk factor for obstetric, fetal and neonataloutcome? A critical review of the literature. J Matern-Fetal Neo M 2007,20(3):189–209.21. Hoffman S, Hatch MC: Depressive symptomatology during pregnancy:evidence for an association with decreased fetal growth in pregnanciesof lower social class women. Health Psychol 2000, 19(6):535–543.22. Steer RA, Scholl TO, Hediger ML, Fischer RL: Self-reported depression andnegative pregnancy outcomes. J Clin Epidemiol 1992, 45(10):1093–1099.23. Kozhimannil KB, Pereira MA, Harlow BL: Association between diabetes andperinatal depression among low-income mothers. JAMA 2009,301(8):842–847.24. Haelterman E, Breart G, Paris-Liado J, Dramaix M, Tchobroutsky C: Effect ofuncomplicated chronic hypertension on the risk of small-for-gestationalage birth. Am J Epidemiol 1997, 145(8):689–695.25. Dayan J, Creveuil C, Herlicoviez M, Herbel C, Baranger E, Savoye C, Thouin A:Role of anxiety and depression in the onset of spontaneous pretermlabor. Am J Epidemiol 2002, 155(4):293–301.26. Mintzes B, Wright JM: Are antidepressants safe in pregnancy? A focus onSSRIs. Therapeut Lett 2010, 76:1–2.27. Mintzes B, Fortin PM, Wright JM: Antidépresseurs et grossesse: Lesinhibiteurs spécifiques de la recapture de la sérotonine. Médecine 2010,6(6):255–257.28. Iqbal MM, Sobhan T, Ryals T: Effects of commonly used benzodiazepineson the fetus, the neonate, and the nursing infant. Psychiatr Serv 2002,53(1):39–49.29. Eberhard-Gran M, Eskild A, Opjordsmoen S: Treating mood disordersduring pregnancy: safety considerations. Drug Saf 2005, 28(8):695–706.30. Ross LE, Grigoriadis S, Mamisashvili L, Vonderporten EH, Roerecke M, RehmJ, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A: Selectedpregnancy and delivery outcomes after exposure to antidepressantmedication: a systematic review and meta-analysis. JAMA Psychiatry 2013,70(4):436–443.31. Nakhai-Pour HR, Broy P, Berard A: Use of antidepressants duringpregnancy and the risk of spontaneous abortion. Can Med Assoc J 2010,182(10):1031–1037.32. Huybrechts KF, Sanghani RS, Avorn J, Urato AC: Preterm birth andantidepressant medication use during pregnancy: a systematic reviewand meta-analysis. PLoS ONE 2014, 9(3):e92778.33. Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH: Selectiveserotonin reuptake inhibitors in pregnancy and congenitalmalformations: population based cohort study. BMJ 2009,339:b3569–b3575.34. Jong GW, Einarson T, Koren G, Einarson A: Antidepressant use inpregnancy and persistent pulmonary hypertension of the newborn(PPHN): A systematic review. Reprod Toxicol 2012, 34(3):293–297.35. Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL: Birth outcomes inpregnant women taking fluoxetine. N Engl J Med 1996, 335(14):1010–1015.36. Costei AM, Kozer E, Ho T, Ito S, Koren G: Perinatal outcome following thirdtrimester exposure to paroxetine. Arch Pediatr Adolesc Med 2002,156(11):1129–1132.37. Laine K, Heikkinen T, Ekblad U, Kero P: Effects of exposure to selectiveserotonin reuptake inhibitors during pregnancy on serotonergicsymptoms in newborns and cord blood monoamine and prolactinconcentrations. Arch Gen Psychiatry 2003, 60(7):720–726.38. Kallen B: Neonate characteristics after maternal use of antidepressants inlate pregnancy. Arch Pediatr Adolesc Med 2004, 158(4):312–316.39. Oberlander TF, Misri S, Fitzgerald CE, Kostaras X, Rurak D, Riggs W:Pharmacologic factors associated with transient neonatal symptomsfollowing prenatal psychotropic medication exposure. J Clin Psychiatry2004, 65(2):230–237.40. Gentile S: Drug treatment for mood disorders in pregnancy. Curr OpinPsychiatry 2011, 24(1):34–40.41. McCauley-Elsom K, Gurvich C, Elsom SJ, Kulkarni J: Antipsychotics inpregnancy. J Psychiatr Ment Health Nurs 2010, 17(2):97–104.42. Bellantuono C, Tofani S, Di Sciascio G, Santone G: Benzodiazepineexposure in pregnancy and risk of major malformations: a criticaloverview. Gen Hosp Psychiatry 2013, 35(1):3–8.43. Hudak ML, Tan RC, Committee On DRUGS, Committee on Fetus andNEWBORN, American Academy of P: Neonatal Drug Withdrawal. Pediatrics2012, 129(2):e540–e560.44. Wang LH, Lin HC, Lin CC, Chen YH, Lin HC: Increased risk of adversepregnancy outcomes in women receiving zolpidem during pregnancy.Clin Pharmacol Ther 2010, 88(3):369–374.45. Reeves WC, Strine TW, Pratt LA, Thompson W, Ahluwalia I, Dhingra SS,McKnight-Eily LR, Harrison L, D'Angelo DV, Williams L, Morrow B, Gould D,Safran MA, Centers for Disease Control and Prevention (CDC): Mental illnesssurveillance among adults in the United States. Morb Mortal Wkly RepSurveill Summ 2011, 60(Suppl 3):1–29.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionHanley and Mintzes BMC Pregnancy and Childbirth 2014, 14:242 Page 12 of 12http://www.biomedcentral.com/1471-2393/14/24246. FDA: Compazine prescribing information: brand of prochlorperazine. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/010571s096lbl.pdf.47. Markus AR, Rosenbaum S: The role of Medicaid in promoting access tohigh-quality, high-value maternity care. Womens Health Issues 2010,20(1 Suppl):S67–S78.48. Bateman BT, Hernandez-Diaz S, Rathmell JP, Seeger JD, Doherty M, FischerMA, Huybrechts KF: Patterns of opioid utilization in pregnancy in a largecohort of commercial insurance beneficiaries in the United States.Anesthesiology 2014. In press.49. Mojtabai R, Olfson M: Proportion of antidepressants prescribed without apsychiatric diagnosis is growing. Health Aff (Millwood) 2011,30(8):1434–1442.doi:10.1186/1471-2393-14-242Cite this article as: Hanley and Mintzes: Patterns of psychotropicmedicine use in pregnancy in the United States from 2006 to 2011among women with private insurance. BMC Pregnancy and Childbirth2014 14:242.Submit your manuscript at www.biomedcentral.com/submit


Citation Scheme:


Citations by CSL (citeproc-js)

Usage Statistics



Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            async >
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:


Related Items