title: Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.
abstract: BACKGROUND
  Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant.
  
  
  OBJECTIVE
  (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy.
  
  
  METHODS
  Retrospective cohort studies.
  
  
  METHODS
  Primary care.
  
  
  METHODS
  Women treated for psychosis who became pregnant, and their children.
  
  
  METHODS
  Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers.
  
  
  METHODS
  Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders.
  
  
  METHODS
  Clinical Practice Research Datalink database and The Health Improvement Network primary care database.
  
  
  RESULTS
  Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy.
  
  
  CONCLUSIONS
  A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage.
  
  
  CONCLUSIONS
  Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics.
  
  
  CONCLUSIONS
  Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs.
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Petersen
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: McCrea
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Cormac J
authors.initials: CJ
authors.lastname: Sammon
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: David P J
authors.initials: DP
authors.lastname: Osborn
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Evans
authors.affiliation: University Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Cowen
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Irwin
authors.initials: I
authors.lastname: Nazareth
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004363:Drug Utilization; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000453:epidemiology; D011320:Primary Health Care; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D006113:United Kingdom; D014635:Valproic Acid / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D014635:Valproic Acid